Poster Session II (Abstracts 730 – 1194) (2024)

¹Institute of Experimental Immunology and Hepatology, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany; ²Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg‐Eppendorf, Hamburg, Germany; ³lnstitute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany

Introduction The gut microbiota plays a crucial role in regulating the physiology of the host, specifically the immune system. Recent evidence suggests, that the gut microbiota is involved in liver diseases such as non‐alcoholic fatty liver disease, alcoholic and viral hepatitis. However, it remains unclear whether the immunological response is modulated by the gut microbiota directly, or indirectly by its metabolites such as short chain fatty acids (SCFAs) or secondary bile salts. Both of which are important signaling molecules in the gut and in the liver. So far, little is known about the influence of gut microbiota in immune‐me‐ diated liver injury. The concanavalin A (ConA) model is a well‐established mouse model of T cell mediated autoimmune hepatits. Therefore, we investigated the role of gut microbiota in ConA‐induced liver injury. Methods Germ free C57BL/6 or broad‐spectrum antibiotic treated FIRxf/ger mice were challenged with ConA. Multiple parameters were analyzed at the initial, peak and recovery phase of ConA‐mediated liver injury. Immunophenotyping was performed via flow cytometry. Microbial composition of feces was analyzed by 16S rRNA sequencing. SCFAs levels were estimated by hepatic expression levels of its receptor (e.g. GPR‐43). Hepatic expression of GPR‐43 as well as several regulators of bile acid metabolism were investigated by RT‐PCR. The influence of SCFAs on immune cell composition was analyzed via FACS analysis after in vitro co‐culture experiments w/o liver sinusoidal endothelial cells (LSECs). Results Germ free C57BL/6 as well as antibiotic treated mice were protected from ConA‐induced liver injury. Antibiotic treatment reduces frequencies of CD4⁺T cells and IL‐10⁺ regulatory T cells (Tregs) following ConA‐treatment. Hepatic expression of GPR‐43 was up‐regulated in response to antibiotic treatment and down‐regulated after ConA‐chal‐ lenge. The same effects was seen for cholesterol 7α‐hydroxy‐ lase (Cyp7A1), which catalyzes the conversion of cholesterol to primary bile acids. The opposite effect could be determined in case of the bile acid membrane receptor TGR5. In vitro experiments indicate that butyrate reduces IFNγ and IL‐10 production by CD4⁺T cells in co‐culture with LSECs. Conclusion We clearly verified a link between gut microbiota and ConA‐induced liver damage. Reduction (via antibiotics) or absence (germ free mice) of gut microbiota led to ameliorated ConA‐damage. This is in line with decreased Tregs in the liver, which is explained by the less severe liver damage. Our results indicate that further analysis of SCFAs and bile salt metabolism is needed to determine its specific function during pathogenesis of liver disease.

Disclosures:

The following people have nothing to disclose: Birgit Schiller, Claudia Wegscheid, Laura Berkhout, Agnieszka E. Zarzycka, Ulrich Steinhoff, Nicole Fischer, Gisa Tiegs

¹Laboratory of Pathology, National Cancer Institute, Bethesda, MD; ²National Institues of Health, Bethesda, MD; ³Liver Disease Branch, The National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; ⁴lnterventional Radiology, Clinical Center, Bethesda, MD; ⁵Immunology Service, Clinical Center, Bethesda, MD

Background: The liver is an immune organ interposed between portal and peripheral venous circulations. Immune aberrancies including altered adaptive immune responses occur in chronic liver disease. These changes have mainly been explored in cells isolated from liver and peripheral venous blood, and their association with liver disease severity is unclear. Here, changes in T cell subset (T_subset) distribution in portal vs. peripheral venous blood of patients with chronic hepatitis C (cHCV) were related to disease severity. Methods: We prospectively studied a cohort of compensated cHCV patients. Subjects underwent percutaneous liver biopsy, direct portal vein cannulation and direct pressure (dPP) measurement. Portal and peripheral blood samples were obtained. CD4+ and CD8+ T cells were measured by multicolor flow cytometry, and categorized as naïve (CD62L+/CD45RA+), central memory (CD62L+/CD45RA‐), effector memory (CD62L‐/CD45RA‐), or effector (CD62L‐/ CD45RA+) cells. Ishak fibrosis score (IF) and dPPwere used as markers of liver disease severity and Spearman's rho (r) was used to correlate disease severity indicators with T_subsetabsolute counts. Results: Of 30 patients enrolled, 29 completed the study (mean age= 57.5, males=63.3%). IF of 0‐2, 3‐4 and 5‐6 was found in 10, 6 and 13 patients, respectively. dPP ranged between 2‐32 mm/Hg. In portal blood (n=28), CD4+ central memory T_subset but none of the CD8+ T _bset, correlated with IF (r=0.56, p=0.001). In peripheral bloocf (n=27), neither CD4+, nor CD8+ T_subset correlated with IF. With increasing dPP, portal blood derived CD4+ central memory T_subset trended towards significance (r=0.37, p=0.06), whereas, none of the CD8+ T_subset showed a significant change. Interestingly, in periph‐ erafolood, CD4+ T_subset did not correlate with dPP but CD8+ effector memory T_subset, showed a negative correlation (r= ‐0.38, p=0.048). Conclusions: CD4+ and CD8+ T_subsets show dynamic changes across liver disease severity. Disease severity associated quantitative changes in CD8+ T_subset and CD4+ T_subset are not only distinct between portal and peripheral venous system, but the CD8+ T_subset changes appear to be confined to the peripheral circulation. This suggests that adaptive immune cell aberrancies in cHCV evolve with liver disease progression, and that the diseased liver contributes to these changes by affecting T cells as they transition from portal to systemic venous circulation.

Disclosures:

The following people have nothing to disclose: Ohad Etzion, Rabab Ali, Christopher Koh, Elliot Levy, David E. Kleiner, Shakuntala Rampertaap, Sergio Rosenz‐ weig, Varun K. Takyar, Ma Ai Thanda Han, Shilpa Lingala, Nancy Fryzek, Vanessa Haynes‐Williams, Theo Heller

¹Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany;²Department of Pediatrics, University Hospital RWTH Aachen, Aachen, Germany; ³Nutrigenomics Consortium, Tl Food & Nutrition, Wageningen, Netherlands; ⁴lnstitute of Pathology, University Hospital RWTH Aachen, Aachen, Germany

Background & Aims: Hepatocellular carcinoma (HCC) is often based on chronic inflammation and a malignant transformation of hepatocytes, resulting in liver fibrogenesis. In this process, subsets of CD4+ T helper (Th) cells are involved, mediating pro‐inflammatory (TH17) or anti‐inflammatory (T regulator (Treg)) effects. T‐cell specific overexpression of the cyclic adenosine monophosphate‐responsive element modulator alpha (CREMα) was previously described to dispose T‐lymphocytes towards a Th 17 phenotype in models of systemic lupus erythematosus or lung inflammation. Additionally, an increased Thl 7 response is associated with a poor prognosis in patients with chronic liver disease (CLD). Therefore we investigated the relevance of Thl7 cells for CLD and its implications for hepatocellular carcinoma (HCC). Methods: Transgenic mice overexpressing CREMα were crossed with hepatocyte‐specific Nemo knockout mice (Nemo^Δhepa) to generate Nemo^Δhepa/CREMα^Tg mice. The impact of CREMα^Tg T‐cells on Nemo^Δhepa mediated CLD progression was examined. To proof the impact of CRE‐ Ma^Tg T cells, adoptive transfer of bone marrow derived cells (BMDCs) and T‐cells was performed. For a comprehensive analysis of T‐cell phenotype NanoString Technology™ and FACs analysis were included. Results: Overexpression of CREMα in T‐cells of NEMO^Δhepa mice diminished serum transaminase levels, associated with reduced numbers of infiltrating CD11 b+ dendritic cells and CD8+ T‐cells. As a consequence fibrosis and HCC development was significantly reduced. Simultaneous adoptive transfer of BMDCs and T‐cells from CREMα^Tg into Nemo^Δhepa mice clearly identified CREMα^Tg T‐cells as essential for improving the course of CLD. Surprisingly, in this scenario, CREMα^Tg T‐cells didn't show a Thl 7 phenotype with IL‐17 production and expression of the linage marker RORγT. In contrast, hepatic T‐cells were characterised by the expression of Treg‐related markers like FOXP3, CTLA4 and TIM3. In vitro, CREMα^Tg T‐cells stimulated with TGFβ and retinoic acid (RA) containing supernatant of activated HSCs, were polarised towards an anti‐inflammatory Treg phenotype. Mechanistically, administration of a specific retinoic acid receptor (RAR)a inhibitor reduced FOXP3+ Treg polarisation. These findings reveal that CREMα^Tg T‐cells are a prerequisite for inducing FOXP3+ Tregs. Conclusion: Our results demonstrate that overexpression of CREMα in T‐cells changes the inflammatory milieu, attenuating initiation and progression of CLD. Unexpected, our study demonstrates that CREMα transgenic T‐cells induced by HSCs shift chronic inflammation in Nemo^Δhepa livers towards a protective Treg response.

Disclosures:

Christian Trautwein ‐ Advisory Committees or Review Panels: Abbvie, MSD, BMS, Gilead, Bayer, AstraZeneca; Speaking and Teaching: Falk, MSD, Abbvie, BMS, Gilead

The following people have nothing to disclose: Antje Mohs, Nadine Hermanns, Kim Ohl, Mark V. Boekschoten, Thomas Longerich, Klaus Tenbrock, Francisco Javier Cubero

¹Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom; ²Clinical Immunology, University of Birmingham, Birmingham, United Kingdom

Background. IL‐17 secreting CD4 T cells (Th 17) have been implicated in autoimmunity and inflammatory disease and provide a link between the innate and adaptive immune responses. IL‐17‐producing T cells are present around bile ducts, but their functional role and mechanism of localization is poorly understood. Methods. Primary human cholangiocytes were assessed for their chemokine and cytokine secretion in response to bacterial products and pro‐inflammatory cytokines including IL‐17. The effect of cholangiocytes on CD4 T cell differentiation and stability was assessed using cholangiocyte‐conditioned media stimulated with or without IL17, TNFα and IFNγ. Results: E.coli and LPS treatment of cholangiocytes stimulated CCL20 secretion that was able to attract CCR6+ Th 17 cells in in‐vitro migration assays. Cholangiocytes secreted Th 17 polarizing cytokines including IL1β, TGFβ and IL‐6 when treated with IL‐17 and CD4 cells showed evidence of polarisation to Th 17 cells when co‐cultured over 7 days with TNFα and IFNγ stimulated or IL‐17 stimulated cholangiocyte supernatant. IL‐17 treatment induced Stat3 dependent proliferation of cholangiocytes but no increase in ICAM‐1 orVCAM‐1 expression. IL‐17 treatment also induced cholangiocytes to secrete IL‐8 and MCP‐1, which could be responsible for the recruitment of neutrophils and macrophages around the bile ducts. Conclusions. Cholangiocytes respond to IL‐17 by proliferating and secreting Th 17 polarizing cytokines, which favours the maintenance of Th 17 lineage in infiltrating CD4 T cells. The secretion of CCL20 and IL‐17 polarising cytokines by cholangiocytes in response to LPS and E coli suggests that the presence of bacteria or their products in inflamed portal tracts may contribute to the maintenance of this polarising microenvironment.

Disclosures:

David H. Adams ‐ Advisory Committees or Review Panels: GSK, Proximagen; Grant/Research Support: Takeda, Biotie Therapies, Novimmune, ChemoCentryx, Novimmune, Biotie Therapies; Patent Held/Filed: biotie therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies, Biotie Therapies

The following people have nothing to disclose: Hannah C. Jeffery, Ricky H. Bhogal, Jane Birtwistle, Solomon Brown, Simon C. Afford, Ye H. Oo

¹National Center Global Health and Medicine, Ichikawa, Japan; ²Showa University, Shinagawa, Japan; ³University of Pennsylvania, Philadelphia, PA; ⁴Hokkaido University, Sapporo, Japan; ⁵Showa University Koto Toyosu hospital, Toyosu, Japan

Background/Aim: It is clinically evident that patients with chronic liver disease have increased immunoglobulins compared to healthy subjects. Regardless of such conditions, patients with liver cirrhosis are immune‐compromised, whose risk of severe bacterial infection is increased according to the progression of Child‐Pugh status. We previously reported that peripheral CD27+ memory B‐cell frequency and functions are significantly decreased in cirrhotic patients (Hepatology 2012) We hypothesized that the dysregulation of B cell differentiation, viability and function is involved in the excessive production of “futile” immunoglobulins. We thus aimed to clarify B cell function in patients with wide range of liver diseases by analyzing the profile of serum immunoglobulin subtypes and B cell gene signatures Method: We retrospectively analyzed IgG, IgA and IgM levels in 527 patients with liver diseases from our medical records and classified depending on etiology and Child‐Pugh score. The five etiological groups are; HCV, HBV, alcohol, NAFLD and the others. Patients with autoimmune hepatic disease (AIH and PBC) were excluded. Using cryopreserved serum, we also performed the immunoglobulin isotyping with Bioplex system. We measured the mRNA levels of activation markers by real‐time PCR in isolated CD27+ memory B‐cells recovered from cirrhotic patients and healthy subjects In addition, we examined the expression of activation‐induced cytidine deaminase (AID), crucial for class‐switch recombination and somatic hypermutation during plasma cell differentiation Results: Cirrhotic patients have elevated serum IgG and IgA regardless of underlying etiologic change Also, the IgG and IgA levels increased in the progression of Child‐Pugh stage. Patients with advanced cirrhosis (Child‐Pugh B and C) tend to have increased IgG1 frequency (p=0.0016), while relative decrease of IgG2 compared to healthy donors (HD) (p=0.0048). The expression of activation markers of memory B‐cell (CD69, CD71, CD80, CD86) in the cirrhosis group was comparable with that in HD However, AID level in memory B‐cell was increased in cirrhotic patients compared to those in HD (p=0.0367) Conclusions: Cirrhotic patients with wide range of etiology show increased immunoglobulin status Enhanced expression of AID in memory B cells and disproportional immunoglobulin profile may account for the “futile” immunoglobulin status of advanced cirrhosis

Disclosures:

David E Kaplan ‐ Grant/Research Support: Bayer Pharmaceuticals, Inovio Pharmaceuticals

The following people have nothing to disclose: Hiroyoshi Doi, Kenichi Morikawa, Junichi Eguchi, Takayoshi Ito, Tatsuya Kanto, Hitoshi Yoshida

¹Centre for Inflammation research, University of Edinburgh, Edinburgh, United Kingdom; ²University of Edinburgh, Edinburgh, United Kingdom; ³Centre for Regenerative Medicine, University of Edinburgh, EH16 5UU, United Kingdom; ⁴University of Bristol, Bristol, United Kingdom

The interplay between macrophages and T cells shapes the inflammatory response An appropriate balance of T cells is essential for the resolution of fibrosis as shown in model of organ rejection after transplantation. T‐cell polarisation results after antigen presentation from professional antigen‐presenting cells to CD4+ T helper lymphocytes. We induced chronic liver fibrosis by carbon tetrachloride injection in mice with defective of the last step of phagocytosis and in their wild‐type counterparts. Our hypothesis is that phagocytosis is instrumental for both antigen presentation and the set‐up of a correct cytokine environment for the correct T cell polarisation to occur Increased damage was observed in mice lacking phagocytic cargo digestion, altogether with an imbalance in macrophage polarisation, tipped to a pro‐inflammatory phenotype Those findings prompted us to investigate the CD4+ T‐cell response. In order to investigate it, livers were harvested at distinct time points after CCI4 suspension. Analysis was carried on using qPCR and immunohistochemistry on total liver extract and liver sections respectively. This study shows that in the absence of a correct phagocytic cargo digestion an impaired Th2 response results. Defect in the production of Th2‐related cytokines such as IL4 was observed in homeostatic conditions also (Il4 mRNA expression in untreated mice lacking phagocytic cargo processing vs. wild type mice: −4 to 5 fold), possibly pointing out to a general defect in the Th2 polarisation (Gata3 mRNA expression untreated mice lacking phagocytic cargo processing vs. wild type mice: −2 fold). Also, more proliferation in the non‐parenchymal compartments was observed in mice lacking the last step of phagocytosis at 72h of recovery (Ki67 immunohistochemistry, 9±2 vs. 12±2 cells/field of view, 20x magnification, n=5−7 mice/group). Further investigation is required to determine the mechanism in which phagocytosis acts on the Th2 response and whether a defective phagocytosis correlates with an uncontrolled expansion of specific T‐cell subtypes in the regenerating liver. Understanding the dynamics that control this relationship may have great impact on the elucidation of novel potential therapeutic targets in the scarring process.

Disclosures:

The following people have nothing to disclose: Lara Campana, Sarah E. Mok, Antonella Pellicoro, Stuart J. Forbes, John P. Iredale

Centre for Liver Research, University of Birmingham, Birmingham, United Kingdom

Introduction: Unregulated inflammation of the liver drives the onset and progression of a range of aetiologically diverse chronic liver diseases and, ultimately, promotes the formation of neoplastic tumours, such as hepatocellular carcinomas (HCC). A key step in hepatic inflammation is the recruitment of leukocytes via hepatic sinusoidal endothelial cells (HSEC) CD151, a member of the tetraspanin family, has previously been shown to play a role in leukocyte recruitment to vascular endothelia; however, the presence of CD151 has not previously been explored in the hepatic sinusoidal endothelium Consequently, an understanding CD151 expression and function in the liver could identify a new therapeutic target for limiting hepatic inflammation. Methods: We used immunohistochemistry, dual colour immunofluorescence co‐localisation studies, qRT‐PCR and western blotting to determine the cell‐specific expression of CD151 in normal liver, chronic liver diseases and HCC. qRT‐PCR and cell‐based ELISA studies were used to determine the regulation of CD151 expression in HSEC by growth factors, proinflammatory cytokines and hepatoma cell line (HepG2) supernatant Flow‐based adhesion assays were used to study the functional role of CD151 in the adhesion of Jurkat cells, a human T cell line, to HSEC monolayers. Results: Increased CD151 protein expression was associated with areas of fibrosis and neovascularisation, particularly in parenchymal liver diseases, such as alcoholic liver disease (ALD) and non‐alcoholic steatohepatitis (NASH), as well as in HCC CD151 was shown to be highly expressed by HSEC in vivo and expression was maintained in cultured HSEC in vitro The expression of CD151 in HSEC was upregulated by stimulation with HepG2 supernatant and tumourigenic growth factors, such as hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). We also found CD151 molecules clustering around adherent T cells following capture from physiological flow by HSEC monolayers Furthermore, function‐blocking antibodies to CD151 significantly reduced adherence of T cells under flow conditions. Conclusion: We demonstrate, for the first time, the expression of CD151 on human sinusoidal endothelial cells and neovessels in a range of chronic liver diseases and HCC. We also demonstrate that CD151 in HSEC is maintained in vitro and can be upregulated by pro‐tumourigenic factors and plays an important functional role in T cell adhesion to HSEC Taken together, these findings further our understanding of hepatic inflammation and lymphocyte recruitment to the liver, during chronic disease and carcinogenesis, and could form the basis of a potential therapeutic target.

Disclosures:

The following people have nothing to disclose: Daniel A. Patten, James C. Wadkin, Sivesh K. Kathir Kamarajah, Chris J. Weston, Shishir Shetty

¹Azienda Ospedalero‐Universitaria Pisana, Pisa, Italy; ²University of Florence, Florence, Italy; ³University of Foggia, Foggia, Italy; ⁴Ospedale Santa Maria Annunziata, Florence, Italy; ⁵Azienda Ospedaliero‐Universitaria di Parma, Parma, Italy; ⁶University of Turin, Turin, Italy; ⁷University of Bari, Bari, Italy; ⁸Unversity Hospital of Messina, Messina, Italy; ⁹University of Palermo, Palermo, Italy; ¹⁰Sapienza University of Rome, Rome, Italy; ¹¹Second University of Naples, Naples, Italy; ¹²Catholic University, Rome, Italy; ¹³University of Cagliari, Cagliari, Italy; ¹⁴University of Padua, Padua, Italy; ¹⁵University of Modena and Reggio Emilia, Modena, Italy; ¹⁶Azienda Ospedaliero Universitaria di Verona, Verona, Italy; ¹⁷University Hospital of Padua, Padua, Italy; ¹⁸University of Bologna, Bologna, Italy; ¹⁹Gragnano Hospital, Naples, Italy; ²⁰Niguarda Hospital, Milan, Italy; ²¹V.Cervello Hospital, Palermo, Italy; ²²Alma Mater Studiorum University of Bologna, Bologna, Italy; ²³University of Salerno, Salerno, Italy; ²⁴University of Milan, Milan, Italy; ²⁵Niguarda Ca' Granda Hospital, Milan, Italy; ²⁶University of Naples Federico II, Naples, Italy; ²⁷University Hospital Catanzaro, Catanzaro, Italy; ²⁸ASMN Reggio Emilia, Reggio Emilia, Italy; ²⁹Bianchi Malacrino‐Morelli Hospital, Reggio Calabria, Italy; ³⁰Fondazione Ospedale Maggiore Policlinico IRCCS, University of Milan, Milan, Italy; ³¹Istituto Superiore di Sanita, Rome, Italy

Background and aims: New DAA treatments for HCV infection are highly efficacious, yet costly. Nevertheless, it is time to move from treating selected prioritized patients to strategies that include treatment of all HCV infected patients To this end a lifetime multi‐cohort model of 8125 real life HCV infected patients, enrolled in the PITER cohort was used to compare two IFN free treatment's policies. Policy 1:Treat all patients of the cohort in any fibrosis stage(F0‐F4). Policy 2: Treat first: patients who are prioritized by the EASL HCV Clinical Practice Guidelines 2015; Wait and treat: the remaining patients when they would reach the F3 stage. Dynamic lifetime HCV disease progression and the related costs were evaluated adapting a Markov model in a lifetime horizon from a health care system perspective. Each real life patient entered the model at the proper age and fibrosis stage and was followed in the model over a lifetime. Total medical costs, quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratios (ICERs) were evaluated. Probabilistic and scenario analyses were performed. Results: In the base‐case analysis (base price of HCV regimen: € 15,000), treating all fibrosis stages vs treating the prioritized patients first, adds: € 31,083,475 (incremental costs) and 3,497 incremental QALYs, for an ICER of € 8,893 per QALY gained. The Monte Carlo scenarios (10,000 simulations) were arranged on a cost‐effectiveness plot and then reported on a cost‐effectiveness acceptability curve (CEAC). ICERs (incremental costs by the incremental QALYs between Policy 1 vs Policy 2) remain cost effective (below € 40,000/QALY) in 91 % of the simulations assumed In the scenario analysis, different ICERs were calculated for fourteen prices' combinations, differentiated by fibrosis staging and the discount rate The base price of IFN‐free treatment regimen (€ 15,000), remained unvaried on time for patients with moderate to severe liver disease stage, whereas decreasing combinations of discount prices in patients with F1/F2 and F0 stage were applied. ICER was very sensitive at price variations for patients at F0 stage For the price levels lower than 60% and 70% of the base price, applied in patients with F1/F2 and F0 respectively, the Policy 1 resulted to be dominant (less costs and greater benefits than Policy 2); policy 1 become cost effective in 97% of the simulations and dominant in 40% of them by the sensitivity analysis Conclusion: Treating HCV infection at any fibrosis stage appeared to improve health outcomes and to be cost‐effective Cost effectiveness increases significantly lowering the treatment's prices in early fibrosis stages.

Disclosures:

Maurizia R. Brunetto ‐ Advisory Committees or Review Panels: Schering‐Plough, Gilead, Janssen, AbbVie; Speaking and Teaching: Roche, Gilead, Bristol‐Myers Squibb, Abbott, Roche, Janssen

Alfredo Di Leo ‐ Advisory Committees or Review Panels: THD; Speaking and Teaching: Abbvie, MSD, Gilead, Roche, Italfarmaco

Giovanni Raimondo ‐ Speaking and Teaching: BMS, Gilead, Roche, Merck, Janssen, Bayer, MSD

Carlo Ferrari ‐ Advisory Committees or Review Panels: Gilead, Roche, Abbvie, BMS, Merck, Arrowhead; Grant/Research Support: Gilead, Roche, Janssen

Gloria Taliani ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead, BMS, Merck, Roche; Speaking and Teaching: ROCHE, Merck, BMS, Gilead, Jannsen, AbbVie

Pierluigi Blanc ‐ Consulting: ABBVIE; Grant/Research Support: GILEAD; Speaking and Teaching: BMS

Giovanni B Gaeta ‐ Advisory Committees or Review Panels: Janssen, Merck, Abbvie, Roche; Speaking and Teaching: BMS, Gilead, merck

Luchino Chessa ‐ Board Membership: Abbvie; Speaking and Teaching: BMS, Jannsen

Erica Villa ‐ Advisory Committees or Review Panels: MSD, Abbvie, GSK, Gilead; Speaking and Teaching: Novartis

Pietro Andreone ‐ Advisory Committees or Review Panels: Janssen‐Cilag, Gilead, MSD/Schering‐Plough, Abbvie, Intercept; Speaking and Teaching: Gilead, BMS Gabriella Verucchi ‐ Advisory Committees or Review Panels: Gilead, Abbvie, Janssen, ViiV; Speaking and Teaching: Merck&Co, Gilead, Bristol Meyers Squibb, Abbvie

Marcello Persico ‐ Advisory Committees or Review Panels: abbvie; Grant/ Research Support: gilead

Massimo Zuin ‐ Board Membership: Abbvie; Speaking and Teaching: Roche

Massimo Puoti ‐ Advisory Committees or Review Panels: GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis; Speaking and Teaching: BMS, BMS, BMS, BMS

Alfredo Alberti ‐ Advisory Committees or Review Panels: Merck, roche, Gilead, Merck, roche, Gilead, Merck, roche, Gilead, Merck, roche, Gilead, Abbvie, Janssen; Grant/Research Support: Merck, gilead, Merck, gilead, Merck, gilead, Merck, gilead, Abbvie, Janssen; Speaking and Teaching: novartis, BMS, novartis, BMS, novartis, BMS, novartis, BMS

Maria G Rumi ‐ Grant/Research Support: MSD; Speaking and Teaching: MSD, BMS, Gilead, Abbvie

The following people have nothing to disclose: Loreta A Kondili, Federica Romano, Matteo Ruggeri, Stefano Rosato, Anna Linda Zignego, Alessia Ciancio, Guglielmo Borgia, Teresa A Santantonio, Antonio Gasbarrini, Elke M Erne, Donatella Ieluzzi, Francesco P. Russo, Maria Vinci, Carmine Coppola, Liliana Chemello, Salvatore Madonia, Gerardo Nardone, Vincenzo De Maria, Marco Massari, Giuseppe Montalto, Giuseppe Foti, Americo Cicchetti, Antonio Craxi, Stefano Vella

¹Epidemiology, Gilead Sciences, Foster City, CA; ²School of Public Health, University of California, Berkeley, Berkeley, CA; ³Clinical Research, Gilead Sciences, Inc., Foster City, CA

Background Curative HCV treatment with IFN‐based regimens has been associated with reduction in the rate of HCV‐associated liver cancer. Whether achieving sustained virologic response following treatment with IFN‐free direct‐acting antiviral (DAA)‐based regimens yields a similar benefit is unknown. The objective of this study was to examine the association of treatment completion with the DAA sofosbuvir (SOF) with risk of incident liver cancer in real‐world data Methods From US administrative claims data from January 1, 2010 through March 31, 2015, we identified adult HCV patients dispensed at least 12 weeks of SOF‐containing therapy who had no evidence of subsequent HCV treatment (N=5,033). For comparison, we identified adult patients diagnosed with HCV without evidence of HCV treatment who had active follow‐up time after SOF approval (N=69,374). All included patients had a minimum of 6 months of enrollment and no evidence of prior liver cancer at baseline Hazard ratios (HRs) estimating risk of incident liver cancer associated with completion of SOF‐containing therapy were calculated after adjustment for baseline confounders using Cox proportional hazards methods. Results Patients completing SOF‐containing treatment were more likely to be >55 years and male, and to have cirrhosis at baseline (34.7% vs. 11.5%), than untreated HCV patients; median follow‐up was shorter in SOF‐completing vs. untreated patients (171 and 328 days, respectively) When stratified by baseline cirrhosis status, absolute cumulative incidence rates (95% confidence interval [CI]) were not different between SOF‐completing and untreated patients: 0.77 (0.40‐1.35) and 0.67 (0.60‐0.75) per 100 person‐years (PY), respectively among non‐cirrhotics, and 3.24 (2.15‐4.68) and 3.67 (3.21‐4.17) per 100 PY, respectively among cirrhotics There was no significant interaction of observed treatment effect with baseline cirrhosis (p=0.53) After adjustment for age, gender, cirrhosis, and other baseline conditions significant at p<0.10, no association was observed between SOF completion and liver cancer (HR=0.96, 95% CI: 0.69‐1.34) This absence of association was observed for both IFN‐free and IFN‐containing SOF treatment regimens (HR=1.01 (95% CI: 0.69‐1.49) and 0.87 (95% CI: 0.49‐1.53), respectively) Conclusions In this real‐world cohort study, completion of SOF‐containing treatment was not independently associated with risk of incident liver cancer, regardless of IFN co‐medication. The strongest risk factors for liver cancer were baseline cirrhosis, older age, and male gender. Future cohort studies should examine longer‐term liver cancer risk following completion of DAA therapy.

Disclosures:

Anand P. Chokkalingam ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Amanda W. Singer ‐ Employment: Gilead Sciences

Anu O. Osinusi ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Laura Telep ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

¹Haifa and Western Galilee Central Laboratories, Clalit Health Services, Nesher, Israel; ²Faculty of Public Health, Haifa University, Haifa, Israel; ³Liver Unit, Carmel Medical Center, Haifa, Israel

Background and Aims: The HCV recombinant strain (St. Petersburg variant) has been reported from several countries but its prevalence (0.5‐2%) may be underestimated by the vast majority of the standard genotyping assays which are based only on the 5′(core) sequencing. So far there was no data on this recombinant virus in Israel The clinical importance of this HCV recombinant genotype lies upon its being mistakenly identified and treated as genotype G2, a treatment which is insufficient for G1 genotype. In this study we report the first cases of recombinant strain 2/1b in Israel. An additional aim was to assess the ability of the Abbott RealTime HCV genotype II RUO (GTII) assay to detect this recombinant strain in comparison to sequence‐based analyses. Methods: 661 stored sera samples of chronic HCV patients (viral load >10⁴ unit/ml) were tested at the Central Laboratory of Haifa and Western Galilee, Clalit Health Services (2014‐2015). HCV genotyping was performed in all samples using the Abbott GTII commercial kit according to the manufacturer instructions. The Abbott GTII assay amplifies and detects portions of both the 5′(core) and 3′(NS5B) regions. The samples in which 2/1b recombinant strain was detected, were further analyzed by sequence‐based analyses. Results: Genotype distribution: G1: 441 (66.7%) [G1a 100 (15.1%), G1b 341 (51.6%)], G2: 33 (5%), G3: 155 (23.4%) and G4: 21 (3.2%) Additional 11 samples (25% of G2! and 1.7% of all 661 sera) were diagnosed as a 2/1b recombinant strain Nine of these 11 patients were immigrants born in the former USSR The mean age was 42 year old Sequence‐ based analyses performed on 4 of these 11 samples showed that these samples are indeed recombinant genotypes 2k/1b chimera with the breaking point between NS2 and NS3 In the meanwhile, the follow ‐up of these patients revealed two patients who relapsed after 24 weeks of Peg/IFN therapy and other two patients showed no response SVR was obtained in one patient after 12 weeks daclatasvir / sofosbuvir therapy. The other patients are ongoing treated by DAAs Conclusions: We have found that the rate of recombinant HCV 2/1 b is 1.7% of all HCV genotypes and 25% of G2 genotype tested in this study Awareness should be raised to this possibility in patients who were identified as G2 HCV patients and it is recommended to use genotyping assays which amplify both the 5′(core) and 3′(NS5B) regions of the HCV genome. The presence of a recombinant virus may affect the outcome of the antiviral treatment.

Disclosures:

Rasha N. Daniel ‐ Employment: Clalit health services

The following people have nothing to disclose: Mira Barak, Orly Azulay, Eli Zuckerman

¹Maladies de l'appareil digestif, Hôpital Huriez, Lille, France; ²Hôpital Cochin, Paris, France; ³Hôpital Purpan, Toulouse, France; ⁴Departement de biostatistiques, Lille, France; ⁵Agence de la biomedecine, Paris, France; ⁶Hôpital Necker, Paris, France; ⁷Hôpital Huriez, Lille, France

In kidney transplantation, before the use of antiviral therapy, HBV and HCV recipients had lower patient and graft survival than non‐infected recipients. In the last two decades, nucleos(t) id analogues have been widely used for HBV patients whereas IFN‐based therapy has been used for smaller proportion of HCV patients. Aims: 1/ to update the impact of HBV and HCV on patient and graft survival; 2/ to assess the prognostic impact of viral control (HBV or HCV). Methods: First, patients and graft survivals were prospectively recorded between 1993 and 2010 in the French nationwide database of kidney recipients according to serological status. Second, we calculated, based on a type I error of 0.05 and a power of 95% that a random sample of at least 580 HBV or HCV patient records should be investigated to evaluate the influence of viral control. Viral control was defined as: low DNA level upon antiviral therapy or inactive carriers for HBV patients; SVR or spontaneous viral eradication for HCV recipients. Results: A/32307 recipients, median age (47.4±14.6 years) were analyzed: 1109 (3.43 %) with positive HCV antibodies, 596 (1.84%) with positive HBsAg and 30602 (94.72 %) non infected patients. HCV kidney recipients had significantly lower 10‐year patient survival (71.1 ±2%) than HBV (81.1 ±2%, p<0.0001) and non‐infected recipients (84.2±3%, p<0.0001) without significant differences between HBV and non‐infected recipients. They also had significantly lower 10‐year graft survival (50.6±1.9%) than HBV (62.3±2.4%, p=0.0001) and non‐infected (66.8.2±0.3%, p<0.0001). After adjustment on age of recipients, age of donors, time of cold ischemia, extent of HLA‐B and DR matching, HCV antibodies remained an independent prognostic factor of 10‐year mortality (HR : 1,75; 95%CI :1.48‐2.1, p<0.0001). B/ 687 patient records have been investigated. Viral control was obtained in almost all HBV recipients (95% of cases) In HCV patients, viral control was observed in 35% of cases among which 17.6% after antiviral therapy In HCV patients, patients with viral control had higher 10‐year patient (84.4±4.6% vs 68±4%, p=0.003) and graft (63,1±5.46% vs 48±3.7%, p=0.003) than those without In multivariate analysis, HCV infection remained independently associated with mortality only in case of viral replication whereas HCV recipients with negative PCR had similar patient and graft survival than non‐infected patients Conclusion: Control of viral replication allows obtaining similar patient and graft survival in HBV and HCV recipients in comparison to non‐infected recipients Conversely, uncontrolled HCV infection is still associated with a decrease in patient and graft survival.

Disclosures:

Hélène Fontaine ‐ Board Membership: Abbvie, Gilead, BMS, Janssen; Independent Contractor: gilead, BMS, MSD, Roche, Janssen

Laurent Alric ‐ Board Membership: Schering Plough, Schering Plough, Schering Plough, Schering Plough; Consulting: MSD; Grant/Research Support: Abbvie; Speaking and Teaching: Roches, BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead, Roches, BMS, Gilead, MSD, Abbvie

Stanislas Pol ‐ Board Membership: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/ Research Support: Gilead, Roche, MSD; Speaking and Teaching: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Roche, MSD, Novartis

Philippe Mathurin ‐ Board Membership: MSD, Janssen‐Cilag, BMS, Gilead, Abvie, Verlyx; Consulting: Roche, Bayer

The following people have nothing to disclose: Benjamin Legendre, Julien Labreuche, Alexandre Louvet, Corinne Antoine, Christophe M Legendre, Marc Hazzan, Nassim Kamar, Sebastien Dharancy, Guillaume Lassailly, Florent Artru, Alain Duhamel

¹Division of Infectious Diseases, Weill Cornell Medical College, Mars, PA; ²VA Pittsburgh /Healthcare System, Pittsburgh, PA

Background: A relatively small proportion of HCV infected persons develop hepatic decompensation and hepatocellular carcinoma even after several years of infection. Predicting who will develop complications can help prioritize treatment decisions. Methods: In the ERCHIVES We calculated three commonly used clinical scores for liver disease severity to determine the risk of overall mortality, hepatic decompensation (HD) and hepatocellular carcinoma (HCC) 1, 3 and 5 years after diagnosis of HCV. We excluded those with HD or HCC at baseline, HIV+ or HBsAg+ and those who received HCV treatment for >28 days. Results: Among 21,327 HCV infected persons identified, <1% of those with lowest CP, MELD or FIB‐4 scores develop HD, HCC or died within 1 year of HCV diagnosis. However, the proportion increases 3‐6 fold for the next stratum of the score at year one and 3 fold at year 3 for the same stratum Mortality, HD and HCC are highest in the higher strata and 5 years after diagnosis (Table) Conclusions: Mortality and complications are infrequent in the first year after HCV diagnosis in persons with low liver disease severity scores, but exponentially increase with increasing time or increasing severity scores These data may help determine the optimal time to initiate treatment to minimize mortality and liver disease complications.

Table. Proportion of persons who died, developed hepatic decompensation or hepatocellular carcinoma 1, 3 and 5 years after diagnosis of HCV infection in ERCHIVES.

Disclosures:

Adeel A. Butt ‐ Grant/Research Support: Gilead, AbbVie

The following people have nothing to disclose: Yanjie Ren

¹Division of Infectious Diseases, University of California San Diego, LA JOLLA, CA; ²Skaggs School of Pharmacy, University of California San Diego, La Jolla, CA; ³Division of Global Public Health, University of California San Diego, La Jolla, CA; ⁴School of Medicine, University of California San Diego, La Jolla, CA

Background: High rates of Hepatitis C (HCV) reinfection following successful treatment among HIV‐infected men who have sex with men (MSM) have been reported in Europe, but no data are available from the US. We assessed the incidence of primary HCV infection and reinfection following successful treatment among HIV positive MSM in San Diego. Methods: We performed a retrospective cohort analysis of HCV primary incidence and reinfection incidence after successful treatment among HIV‐infected MSM during 2008‐2016 at the largest HIV clinic in San Diego (UCSD Owen Clinic). Incident HCV infection was assessed among HIV‐infected MSM with a negative anti‐HCV test between 2008 and 2016, and defined as any positive anti‐HCV or HCV‐RNA test after the start of follow‐up. Re‐infection was defined as a positive HCV RNA PCR test after the date of sustained viral response (SVR) among HIV/HCV‐coinfected MSM treated for HCV between 2008 and 2014. For the re‐infection analysis patients were censored at reinfection or their last negative test before April 2016. Incidence was calculated using survival time methods Results: Among 1,092 baseline negative patients between 2008 and 2016, 40 seroconversions occurred over 3,4340 person‐years at risk, leading to an overall primary HCV incidence of 1.16 per 100 person‐years(/100py) (95%CI 0.85,1.59). During this same time period, among 43 HIV‐infected MSM who achieved SVR following HCV treatment, 3 became re‐infected after a median time of 2.7 years from the date of SVR. Over 103.9 person‐years of follow‐up, the estimated reinfection rate was 2.89/100 py (95% CI: 0.60, 8.44). For two individuals, reinfection occurred through injecting drug use (reported sharing syringes and drug‐preparation equipment since SVR). The third individual did not have any history of drug use All three HCV re‐infected patients had well controlled HIV infection. Conclusions: HCV reinfection incidence among HIV‐infected MSM in San Diego is 2‐3 fold higher than primary HCV incidence Increased efforts at preventing reinfection post‐treatment among HIV‐infected MSM are required.

Disclosures:

Natasha K. Martin ‐ Grant/Research Support: Gilead; Speaking and Teaching: AbbVie, Merck, Gilead

David L. Wyles ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, AbbVie; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb, AbbVie, Tacere

Charles Hicks ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead Sciences, Merck, Janssen Virology, ViiV ‐ GSK

The following people have nothing to disclose: Antoine Chaillon, Thomas C Martin, Davey M Smith, Sanjay R Mehta, Craig Ballard, Bradford Colwell, Francesca Torriani, Lucas Hill, Christopher Mathews, Edward R Cachay

¹Experimental Medicine and Surgery, University of Rome “Tor Vergata”, Rome, Italy; ²Hepatology Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy; ³lnfectious Diseases Unit, Pescara General Hospital, Pescara, Italy; ⁴Infectious Diseases Unit, Sant'Andrea Hospital ‐ “Sapienza” University, Rome, Italy; ⁵Infectious Diseases Unit, University Hospital of Rome “Tor Vergata”, Rome, Italy; ⁶Tropical Diseases, Umberto I Hospital ‐“Sapienza” University, Rome, Italy; ⁷Clinical Microbiology, Virology and Bioemergencies, ASST Fatebenefratelli Sacco, Milan, Italy; ⁸Clinical and Experimental Medicine, University of Sassari, Sassari, Italy; ⁹Hepatology Unit, San Camillo Forlanini Hospital, Rome, Italy; ¹⁰Division of Hepatology, IRCCS AOU San Martino ‐ IST, Genoa, Italy; ¹¹Infectious Diseases Unit, IRCCS AOU San Martino ‐ IST, Genoa, Italy; ¹²Gastroenterology, “P. Giaccone” University Hospital, Palermo, Italy; ¹³Molecular Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; ¹⁴Gastroenterology, «Federico II» University, Naples, Italy; ¹⁵Gastroenterology, Catholic University of Rome, Rome, Italy; ¹⁶Hepatology Unit, Pescara General Hospital, Pescara, Italy; ¹⁷Medicine and Surgery, University of Bologna, Bologna, Italy; ¹⁸Hygiene Unit, IRCCS AOU San Martino ‐ IST, Genoa, Italy; ¹⁹Infectious Diseases Unit, Second University of Naples, Naples, Italy; ²⁰Infectious Diseases Unit, “Sapienza” University, Latina, Italy; ²¹Infectious Diseases Unit, Ospedale di circolo di Busto Arsizio, Varese, Italy; ²²Department of Biomedical, Metabolic and Neural Sciences, NOCSAE Baggiovara, Baggiovara, Italy; ²³Infectious Diseases Unit, S. Salvatore Hospital, L'Aquila, Italy; ²⁴Hospital Niguarda Ca'Granda, Milan, Italy; ²⁵Infectious Diseases Unit, Umberto I Hospital ‐“Sapienza” University, Rome, Italy; ²⁶1st Division of Infectious Diseases, ASST Fatebenefratelli Sacco, Milan, Italy; ²⁷Unit of Infectious Diseases, Laboratory of Microbiology and Virology, “Amedeo di Savoia” Hospital, Turin, Italy

Aim: Natural resistance‐associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). We investigate the frequency of natural RASs, and the role of NS5A‐RASs on treatment efficacy, in a large real‐life database including the 4 main HCV‐GTs. Methods: RASs in NS3 (N=1032), NS5A (N=833) and NS5B (N=496) were analysed in 1193 HCV‐infected DAA‐naïve patients (pts). Sanger‐sequencing was performed by home‐made protocols on 714 GT1a, 989 GT1b, 135 GT2c, 333 GT3a, 24 GT4a and 166 GT4d samples. RASs with fold‐change ≥100 were defined as major. Results: Overall, 415/1193 (35%) pts showed natural RASs, independently by cirrhosis, but with important differences for GT/subtypes. GT1a, GT1b and GT4a frequently showed NS3 RASs (52‐20‐36%, respectively), with high prevalence of 80K in GT1a (17%). The 80K was never found in GT4. Major RASs D168A/E/T/V had 3% prevalence in GT2c and 4% in GT4d. Also in NS5A, GT1a, GT1b and GT4a showed the highest prevalence of RASs (10‐31‐38%, respectively). Major NS5A RASs were detected in 10% GT1a (28V, 30H/R, 31M, 93C/H), 9% GT1b (30R, 93H), 5% GT2c (31M, 93H), 4% GT3a (93H) and 2% GT4d (30S). The most common major NS5A RAS was 93H. In NS5B, the major sofosbuvir 282T RAS was never found, while the putative RASs 159F and 316N were exclusively detected in GT1b (13% and 19%) often in association (phy=0.67, p<0.001 by covariation analysis). Notably, the prevalence of 159F and 316N was higher in interferon+ribavirin‐experienced (7‐11%, respectively), than in naïve pts (3‐4%; p=0.07 and p=0.02, respectively). Among 372 pts with resistance test in all 3 genes, 10% showed multiple RASs. The most prevalent association was NS3+NS5A RASs (3%, mainly GT1 and 4). Only 2 GT1b pts showed RASs on 3 drug‐targets. Lastly, 138 pts treated with a NS5A‐in‐ hibitor were studied to evaluate the potential role of natural NS5A‐RASs Among 26 non‐cirrhotic pts, none had major RASs, and all 4 with baseline minor NS5A RASs (GT1b: 30Q, 31M, 58S, 92T) reached a sustained viral response (SVR12). Among 112 cirrhotic pts, 4 showed major NS5A RASs (fold‐ change >1000). Two of them, (GT1b:93H; GT4d:30S) were treated with not‐recommended regimens, without ribavirin, and experienced virological failure On the contrary, the other 2 (GT1b:93H; GT1a:30R) received a recommended‐regimen with ribavirin and reached SVR Conclusions: Natural RASs are common across all HCV‐GTs, and up to 10% of pts show multiple‐class resistance, though only the so‐called major mutations seem to have a clinical relevance. Thus, qualitative identification of only major natural RASs (rather than all) is required to properly guide DAA‐based therapy.

Disclosures:

Laura A. Nicolini ‐ Board Membership: Abbvie; Speaking and Teaching: Abbvie, Gilead, MSD

Pietro Andreone ‐ Advisory Committees or Review Panels: Janssen‐Cilag, Gilead, MSD/Schering‐Plough, Abbvie, Intercept; Speaking and Teaching: Gilead, BMS

Dante Romagnoli ‐ Advisory Committees or Review Panels: Abbvie Massimo Puoti ‐ Advisory Committees or Review Panels: GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis; Speaking and Teaching: BMS, BMS, BMS, BMS

Giuliano Rizzardini ‐ Grant/Research Support: msd, gilead; Speaking and Teaching: bms, msd, gilead, abbvie, janssen

Gloria Taliani ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead, BMS, Merck, Roche; Speaking and Teaching: ROCHE, Merck, BMS, Gilead, Jannsen, AbbVie

Massimo Andreoni ‐ Advisory Committees or Review Panels: Gilead, BMS, Janssen Tibotec, AbbVie, ViiV; Management Position: MSD

Mario Angelico ‐ Advisory Committees or Review Panels: Gilead, Janssen; Grant/Research Support: Roche; Speaking and Teaching: GSK, Roche, Gilead, Novartis, BMS, Bayer

Francesca Ceccherini‐Silberstein ‐ Speaking and Teaching: Merck Sharp & Dohme, Gilead, Janssen, Abbvie, ViiV, Roche diagnosticis, BMS The following people have nothing to disclose: Valeria Cento, Maria Chiara Sorbo, Ada Bertoli, Ilaria Lenci, Ennio Polilli, Chiara Masetti, Laura Gianserra, Elisabetta Teti, Elisa Biliotti, Carlo F. Magni, Marianna Aragri, Valeria Micheli, Michela Melis, Simona Marenco, Vincenza Calvaruso, Stefania Paolucci, Fausto Baldanti, Filomena Morisco, Massimo Siciliano, Valeria Pace Palitti, Bianca Bruzzone, Nicola Coppola, Tina Ruggiero, Miriam Lichtner, Barbara Menzaghi, Nerio lapadre, Velia Chiara Di Maio, Francesco De Leonardis, Martina Milana, Pierluigi Cacciatore, Alessandro Pieri, Loredana Sarmati, Simona Landonio, Antonio Gasbarrini, Antonio Craxi, Vincenzo Vullo, Adriano M. Pellicelli, Sergio Babudieri, Caterina Pasquazzi, Giustino Parruti, Carlo F Perno

¹Center For Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA; ²Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA; ³Maple Health Group, LLC, New York, NY; ⁴Center for Outcomes Research in Liver Disease, Washington, DC

BACKGROUND AND AIM: Hepatitis C virus (HCV) is the most common cause of cirrhosis, hepatocellular carcinoma (HCC) and indication for liver transplantation (LT) in the United States. Recent advances in HCV have brought about anti‐HCV regimens with sustained virologic response (SVR) rates of 98%. Although general population screening has not previously been found to be cost‐effective, re‐assessment of this strategy for the US population must be considered. Our aim is to compare the cost effectiveness of three screening strategies for HCV: 1) Screen all (SA) 2) Screen based on Birth Cohort Screening (BCS) and 3) Screen based on risks regardless of age (HRS). METHODS: A decision‐analytic Markov model estimated the natural history of HCV and evaluated the cost‐effectiveness of three HCV screening strategies (1) SA, 2) BC and 3) HRS over a lifetime horizon for the US general population. Based on age and risk status, 16 cohorts were modelled. Health states included Fibrosis stages 0 to 4, decompensated cirrhosis, HCC, LT, post‐LT, and death The probability of progression to downstream liver‐related complications was based on presence or absence of virus (SVR) HCV antibody prevalence and the % of high risk patients varied by the specific cohort Treatment was with approved all‐oral DAAs; the exact regimen and duration was based on genotype and stage of liver disease (cirrhosis and non‐cirrhosis) Across all cohorts, 86% were assumed to be seen annually by a primary care provider; 76.6% of HCV Ab+ patients had detectable HCV RNA and 28% of CHC patients were aware of their infection. SVR rates, transition probabilities, utilities, and costs were derived from the literature. Incremental cost effectiveness ratios were compared between SA and the other two screening strategies One‐way sensitivity analyses tested the impact of key model drivers Results: The 3 screening strategies led to identification of new cases of HCV: (SA: 1 73 million, BCS: 1.16 million and HRS: 0.38 million). The strategy to Screen All costs $294.0 billion and leads to 26.5 million QALYs while BCS and HRS cost $300.8 billion and $318.8 billion with 25.4 and 24.5 million QALYs. Compared to BCS, Screen All led to an additional 1.1 million QALYs and saved $6.78 billion while compared to HRS, SA led to 2.0 million additional QALYs and saved $24.8 billion In this context, the SA strategy dominated both the BCS and HRS strategies with additional QALYs and cost savings. CONCLUSIONS: In the era of highly effective anti‐viral regimens with all oral DAAs, screening the entire U S population and treating those with active viremia is projected to be cost‐saving.

Disclosures:

Deidre Blissett ‐ Consulting: maple health group Rachel Beckerman ‐ Consulting: Gilead Sciences

The following people have nothing to disclose: Zobair M. Younossi, Rob Blissett, Linda Henry, Youssef Younossi, Sharon Hunt

¹Anatomie Pathologique, APHP, Hôpital St Antoine, Paris, France; ²Sorbonne Universités, UPMC Univ Paris 06, Paris, France; ³Unité de recherche clinique, APHP, Hôpital Henri Mondor, Créteil, France; ⁴Université Paris 13, Sorbonne Paris‐Cité, Bobigny, France; ⁵INSERM UMR_S 938 centre de recherche Saint Antoine, Paris, France; ⁶Anatomie Pathologique, APHP, Hôpital Beaujon, Clichy, France; ⁷Anatomie Pathologique, APHP, Hôpital Cochin, Paris, France; ⁸Anatomie Pathologique, CHU Bordeaux, Bordeaux, France; ⁹Anatomie Pathologique, CHU Toulouse, Toulouse, France; ¹⁰Anatomie Pathologique, Institut de Biologie et de Pathologie, Grenoble, France; ¹¹Selarl Diag, Nice, France; ¹²ANRS, Paris, France; ¹³Anatomie Pathologique, APHP, Hôpital Jean Verdier, Bondy, France; ¹⁴Clinical epidemiology and ageing, Université Paris Est Créteil, Créteil, France; ¹⁵Hépatologie, APHP, Hôpital Jean Verdier, Bondy, France

Introduction: Aberrant expression of biliary markers, such as cytokeratin 7 (CK7) and epithelial cell adhesion molecule (EpCAM) is thought to reflect an abnormal regeneration recruiting hepatic progenitor cells. We aimed to describe the expression of biliary markers by hepatocytes in patients with compensated HCV‐related cirrhosis and to investigate its potential influence on decompensation events and hepatocellular carcinoma occurrence. Patients and methods: Among 1323 patients with Child‐Pugh A, HCV‐related cirrhosis enrolled in the French prospective ANRS CO12 CirVir cohort, we selected the patients with an available liver biopsy, performed within 2 years before inclusion. Liver biopsies were re‐assessed for activity grade and potential steatohepatitis. CK7 and EpCAM immunostaining was assessed independently by 2 pathologists. Biopsies were considered positive for CK7 when at least 2 foci of more than 5 hepatocytes were observed, and categorized as extensive when one or several cirrhotic nodules showed positive staining in more than 30% of hepatocyte. EpCAM was considered positive when at least one foci of hepatocyte was stained. Patients were prospectively followed. The influence of biliary markers on decompensation events (ascites, hepatic encephalopathy, gastro‐intestinal bleeding) and hepatocellular carcinoma occurrence was studied using univariate analyses and Cox's multivariate analysis. Results : Among 337 patients eligible for the study (men 67%, mean age 49 y), biopsies showed CK7+ hepatocytes in 197 (58%) patients. Among them, the staining was extensive in 40 (12%). Biopsies were positive for EpCAM in 203 patients (61%). The expression of both markers was associated with with a lower platelet count, a higher AFP level and with histological steatohepatitis. During follow‐up (55.2 months [36‐72]), 47 patients (14%) experienced at least one decompensation event and HCC was diagnosed in 37 patients (11%). An extensive CK7 staining was independantly associated with the occurrence of a decompensation event (HR: 3.21 [1,41 ;7,29], p=0,005), along with a low albumin level and the absence of sustained virological response. EpCAM expression was independantly associated with HCC occurrence (HR : 2.40 [1,09 ;5,31 ],p=0,03), along with older age and low prothombin time Steatohepatitis, observed in 42% of biopsies, was not associated with subsequent decompensation or to HCC occurrence. Conclusion: Aberrant expression of CK7 and EpCAM by hepatocytes, assessed on liver biopses of patients with compensated HCV‐related cirrhosis, reflects a cirrhosis stage more prone to develop cirrhosis complications.

Disclosures:

Nathalie Ganne‐Carrié ‐ Advisory Committees or Review Panels: Roche; Speaking and Teaching: BMS, Gilead, Bayer

Françoise Roudot‐Thoraval ‐ Advisory Committees or Review Panels: Roche, gilead; Consulting: LFB biomedicaments; Speaking and Teaching: gilead, Janssen, BMS, Roche, Abbvie

The following people have nothing to disclose: Dominique Wendum, Richard Layese, Valerie Bourcier, Fatiha Merabtene, Carole Cagnot, Emmanuel Sauce, Pierre Bedossa, Benoit Terris, Janick Selves, Paulette Bioulac‐Sage, Nathalie Sturm, Christophe Sattonnet, Pierre Nahon, Marianne Ziol

¹Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM; ²Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ³Clinical Pharmacy, University of California San Francisco, San Francisco, CA; ⁴Psychiatry, University of California San Francisco, San Francisco, CA; ⁵Department of Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA

Hepatitis C virus (HCV) screening has taken on new importance as a result of updated guidelines and new curative therapies. Rew studies have assessed HCV in homeless populations including women. The SHADOW cohort in San Francisco recruited and studied homeless and unstably housed women; sampling was systematically conducted at free meal programs, homeless shelters, and low‐cost single room occupancy hotels, and HIV‐infected women were oversampled. Study inclusion criteria included female sex, age >=18 years, and a lifetime history of housing instability (slept in a public place, a shelter, or stayed with a series other people because they had no other place to sleep). In this paper, we estimated: (1) prevalence and correlates of HCV exposure; (2) the proportion who were unaware of their status; and (3) assessed correlates of both outcomes. Among 246 women, 45.9% were anti‐HCV positive, of whom 61.1% were HIV coinfected. Consistent with the recruitment strategy, just over half of the sample (n=127; 51.6%) was HIV‐infected. A majority (72%) of the women were in the ‘baby‐boomer’ cohort (born between 1945 and 1965); 19% reported recent (past 6‐months) injection drug use (IDU). Factors independently associated with anti‐HCV positivity were: being born in 1965 or earlier (Adjusted Odds Ratio ((AOR) 3.94; 95%CI: 1.88, 8.26), a history of IDU (AOR 4.0; 95%CI: 1.68, 9.55), and number of psychiatric diagnoses (AOR 1.16; 95%CI: 1.08, 1.25).Women with symptoms of current depression had lower adjusted odds of HCV seropositivity (AOR 0.24; 95% CI: 0.12, 0.48). Overall, 26.8% reported never being HCV tested, and among anti‐HCV positives, 27.4% were unaware of their status Factors independently associated with women not knowing their HCV status (controlling for birth cohort status and IDU) included: lower income (per $100 increase), AOR; 0.78 (95%CI: 0.65, 0.94); fewer psychiatric diagnosis (per diagnosis), AOR: 0.80 (95%CI: 0.70, 0.95); and any recent cocaine use (yes vs. no), AOR; 5.63 (95%CI: 1.16, 27.36). Results fill an important gap in information regarding HCV among homeless women, and confirm the need for enhanced screening in this population where a high proportion are baby‐boomers and have a history of drug use and psychiatric problems. Due to their age and risk profile, there is a high probability that women in this study have been infected for decades, and thus have significant liver disease. The association with mental illness and HCV suggests that in addition increased screening, augmenting mental health care and support may be needed to enhance treatment success.

Disclosures:

Kimberly Page ‐ Grant/Research Support: NIH, Gilead, CDC

The following people have nothing to disclose: Michelle Yu, Jennifer Cohen, Jennifer Evans, Martha Shumway, Elise Riley

¹School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; ²Department of Hepatology, Sir Charles Gairdner Hospital, Perth, WA, Australia; ³Department of Anatomical Pathology, PathWest, QEII Medical Centre, Perth, WA, Australia; ⁴Department of Microbiology, Path‐West, QEII Medical Centre, Perth, WA, Australia; ⁵Department of Biochemistry, Pathwest, QEII Medical Centre, Perth, WA, Australia; ⁶School of Medicine, The University of Notre Dame Australia, Perth, WA, Australia

Introduction: Hepascore is a serum test that provides clinically useful data regarding the stage of liver fibrosis and subsequent clinical outcomes in chronic liver disease. The aim of this study was to determine if the change in Hepascore results over time (delta Hepascore) could accurately predict the change in risk of liver related death (LRD), hepatocellular carcinoma (HCC), liver decompensation (LD) and composite endpoint (LRD, HCC, LD) in HCV infection. Methods: 353 chronic hepatitis C patients who attended the Department of Hepatology, Sir Charles Gairdner Hospital, Western Australia from 1992 to 2012 and had two or more Hepascore tests performed were studied The ability of a baseline and delta Hepascore test to predict liver related outcomes was assessed using univariate and multivariate Cox regression, AUROC and Kaplan‐Meier analysis. Results: During 1944 patient years follow up 28 (7.9%) developed hepatocellular carcinoma, liver decompensation, and/or liver related death. Baseline Hepascore (p<0.001) and delta Hepascore (p=0.044) were independently associated with the composite endpoint A baseline Hepascore >0.75 was associated with a significant increase in LRD (p=0.001), LD (p=0.004) and HCC (p=0.001). Patients with a baseline Hepascore >0.75 and a subsequent improvement in delta Hepascore (>‐0.1) had a significantly decreased risk of LRD (p=0.048), LD (p=0.04) and composite endpoint (p=0.004) compared to those with a baseline Hepascore of >0.75 and a stable Hepascore value (delta ± 0.1) or a deteriorated Hepascore value (delta >0.1) The optimum time interval between Hepascore tests was determined by comparing those with improved delta Hepascore to those with stable or worse delta Hepascore The combination of baseline Hepascore and delta Hepascore was significantly predictive of improved liver related outcomes only when the time between tests was > 1 year (p=0.03). Conclusion: This study showed that improved Hepascore values were significantly associated with reduced rates of liver‐related mortality and morbidity These findings have implications for patient management following HCV eradication and may determine the time for reduced need for variceal and HCC screening.

Disclosures:

Angus W. Jeffrey ‐ Patent Held/Filed: UWA

Leon A. Adams ‐ Patent Held/Filed: Quest diagnostics

The following people have nothing to disclose: Yi Huang, Bastiaan de Boer, Gerry C. MacQuillan, David J. Speers, John Joseph, Gary P. Jeffrey

¹Kaiser Permanente, San Diego, CA; ²Department of Medicine, Inova Fairfax Hospital, Fairfax, VA; ³Department of Research and Evaluation, Kaiser Permanente, Pasadena, CA; ⁴Pharmacy Analytical Sevices, Kaiser Permanente, Downey, CA

Background: The 2016 Global Viral Hepatitis Strategy has set a goal to eliminate chronic hepatitis C (HCV) by 2030. To attain this goal, the health care community will need to treat large numbers of patients previously diagnosed with HCV but in whom treatment was deferred due to contraindications or potential adverse effects of the previous interferon‐based therapy. A better understanding of the estimated number of persons who are diagnosed but not yet treated for HCV will allow for improved planning and budgeting for future care of this large population. Objective: To analyze demographic and comorbid conditions in persons treated vs not treated for HCV with interferon‐based therapy and to identify significant predictors of not receiving treatment for HCV. Methods: This is a retrospective cohort study at Kaiser Permanente Southern California (KPSC), a large Health Maintenance Organization including approximately 4 million members. Inclusion criteria: ≥ 18 years old with a diagnosis code or a positive lab test result for HCV RNA 1/1/2002‐12/31/2013 and ≥ 12 months continuous membership before and after index date. Index date was defined as the date of the first treatment course or first HCV diagnosis by ICD ‐9 code or positive HCV RNA test. Exclusion criteria: HCV diagnosis after 1/1/2013 and/or a diagnosis of hepatocellular carcinoma (HCC) on or before index date. Diagnosis codes and/or lab tests for comorbid illnesses representing relative or absolute contraindications to HCV treatment with interferon‐based therapy were determined. Multivariate logistic regression was used to determine predictors of treatment vs non‐treatment. Results: 5,203 patients received treatment and 19,765 did not receive treatment. Demographics and factors associated with not receiving treatment are shown in Table 1 Conclusion: This large epidemiological study identifies the largest patient categories who remain untreated for HCV and will help in budgeting and planning for future treatment of this population with new, well tolerated therapy.

Factors associated with NOT receiving HCV

Disclosures:

Lisa M. Nyberg ‐ Grant/Research Support: Merck, Gilead, Abbvie T. Craig Cheetham ‐ Grant/Research Support: BMS

Anders H. Nyberg ‐ Grant/Research Support: Gilead paid to institution, Abbvie paid to institution

The following people have nothing to disclose: xia Li, Su‐Jau Yang, Kevin Chiang, Susan Caparosa, Zobair M. Younossi

¹Institute of Clinical Medicine, National Yang‐Ming University, Taipei, Taiwan; ²Faculty of Medicine, National Yang‐Ming University, Taipei, Taiwan; ³Genomics Research Center, Academia Sinica, Taipei, Taiwan; ⁴Global Health Economics and Outcome Research, Bristol‐Myers Squibb, Princeton, NJ; ⁵MacKay College of Medicine, Taipei, Taiwan; ⁶The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine,, Ichikawa, Japan; ⁷Academia Sinica, Taipei, Taiwan

BackgroundWisteria floribunda agglutinin‐positive Mac‐2 binding protein (M2BPGi) was reported as a noninvasive marker of liver fibrosis and a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis C (CHC) patients. This study aimed to assess time‐dependent associations between M2BPGi and HCC development in CHC patients using samples collected during long‐term follow‐up. Methods All participants in this study were from the R.E.V.E.A.L.‐HCV cohort. Serum M2BPGi levels were evaluated in a total of 1, 161 samples consisted of 137 HCC cases and 725 controls. There were 82 cases and 86 controls with serial samples collected at various times throughout follow‐up. Associations of M2BPGi and HCC were analyzed using multivariate logistic regression models and further stratified according to time between sample collection and HCC diagnosis. Areas under the receiver operating characteristic (AUROCs) curves were used for evaluating prediction accuracy of models that integrated M2BPGi and other risk factors in predicting HCC risk. Results M2BPGi levels in samples closer to HCC diagnosis were higher than that collected farther from HCC diagnosis. However, M2BPGi levels were consistently low over time in control samples. The analysis using all samples collected at various occasions showed that M2BPGi levels were associated with HCC risk in a dose‐dependent manner after adjustment of gender, age, serum ALT, AST, AFP, HCV RNA levels, and HCV genotype. The adjusted odds ratio (95% CI) was 2.32 (1.57‐3.43), 3.57 (1.83‐6.95), and 10.36 (5.37‐20.00), respectively, for M2BPGi 1‐2, 2‐3, and ≥3 COI compared with those with <1 COI as the referent. When stratified by time of sample collection to HCC diagnosis, associations between M2BPGi levels and HCC were strongest for the short‐term period, and decreased with longer time. Compared to M2BPGi levels <1 COI, adjusted odds ratios (95% CI) for M2BPGi levels ≥3 COI were 38.6 (12.9‐115.2), 7.48 (2.522.5), 3.95 (1.2‐12.6) and 3.21 (1.0‐10.3), respectively, for predicting HCC within 1‐3 years, 3‐6 years, 6‐12 years, and ≥12 years; AUROCs incorporating M2BPGi levels and other predictors were 0.96, 0.92, 0.82 and 0.80, respectively, for prediction of HCC within 4 periods. Conclusion M2BPGi levels significantly predict HCC development in patients with chronic hepatitis C. The associations and prediction accuracy are stronger for samples collected closer to HCC diagnosis than those collected farther from HCC diagnosis.

Disclosures:

Yong Yuan ‐ Employment: Bristol Myers Squibb Company

The following people have nothing to disclose: Chia‐Ling Chang, Liang‐Chun Chen, Hui‐Han Hu, Yu‐Ju Lin, Jessica Liu, Chin‐Lan Jen, Chien‐Yu Su, Cheng‐Tse Chiang, Sheng‐Nan Lu, Li‐Yu Wang, Masaaki Korenaga, Masashi Mizokami, Chien‐Jen Chen, Mei‐Hsuan Lee, Hwai‐I Yang

¹Mt. Sinai Healthcare System, New York, NY; ²Epividian, Inc., Durham, NC; ³Carolinas Healthcare System, Charlotte, NC

Purpose: HIV+ populations are at greater risk for HCV due to shared modes of transmission. Compared to HCV‐monoinfection, HIV/HCV is more likely to result in fibrosis and cirrhosis. High rates of cure are now possible for HIV/HCV patients due to modern direct‐acting antivirals (DAAs). This analysis evaluates HCV testing and treatment patterns in a real‐world setting to identify opportunities for improved outcomes in coinfected patients. Methods: Using the OPERA database, a collaboration of caregivers at 79 clinics in 15 states, HIV+ individuals initiating HIV antiretroviral therapy (ART) for the first time between 1/1/2007 and 3/31/2015 were identified, and followed until data freeze (04/28/2016), death, or loss to follow‐up. Prospectively collected data were extracted from electronic health records. Results: Out of 9,190 HIV+ treatment‐naive patients, 91% were evaluated for HCV prior to ART initiation; 7,837 (85.3%) were HCV antibody‐negative (Ab‐), 472 (5.1%) were HCV+ (by viral load, diagnosis or treatment record), and 26 (0.3%) had a history of resolved HCV. After starting ART, 4,54б (58%) of the 7,837 HCV Abpatients were reevaluated for HCV, resulting in 101 new HCV diagnoses including 5 confirmed seroconversions. Of the 472 baseline HCV+ cases, 235 (50%) were diagnosed in the DAA era (2011 or later). Only 26% (n=123) were ever treated for HCV, most commonly after HIV ART initiation (n=109, 89%) and in the DAA era (n=86, 79%) Median time between HCV diagnosis and treatment was 29 months (IQR: 12, 69). Overall, 72% of the treated cases received DAA‐based therapy, including 99% treated in 2014 or later. Conclusion: Most patients in this ART‐naïve HIV population were evaluated for HCV While HCV treatment was more common in the DAA era, the majority of cases remained untreated. Treatment delays were also commmon. Given the importance of controlling HCV disease progression in coinfected patients and the existence of effective therapies, greater effort should be made to treat all coinfected patients, and to continue monitoring for HCV among HIV‐monoinfected patients after baseline.

Disclosures:

Douglas T. Dieterich ‐ Advisory Committees or Review Panels: Gilead, BMS, Abbvie, Janssen, Merck, Achillion

The following people have nothing to disclose: Cassidy Henegar, Jennifer Fusco, Philip Lackey

4th dept. of medicine, Wilheminenspital, Vienna, Austria

Liver elastography is widely used to assess liver fibrosis in patients with chronic hepatitis C and has also been recommended to monitor regression of liver fibrosis after successful antiviral therapy. We studied early changes of liver stiffness after initiation of antiviral treatment. The study population comprised 53 patients with chronic hepatitis C (mean age ± SD: 49.4 ± 10.7 years; METAVIR fibrosis stage F2, n=23; F3, n = 12; F4, n = 18; genotype (GT) 1, n = 32; GT3, n = 17; GT4, n = 4; mean BMI ± SD: 25.1 ± 3.8). All patients were treated with interferon‐free all oral regimens. Prior to therapy and 1‐6 weeks after initiation of antiviral treatment fibrosis stage was assessed by transient elastography using the Fibroscan® 502 Touch device with the M‐probe (Echosens, Paris, France) and classified according to the METAVIR scoring system. Cut‐off values for liver stiffness were defined as 7.1 kPa for F > 2, 9.5 kPa for F > 3 and 12.5 kPa for F = 4 [4]. Mean liver stiffness at baseline was 14.69 ± 11.15 kPa and decreased to 12.41 ± 9.83 kPa at follow‐up Fibroscan® performed between week 1 and week 6 (p=0.006). When the same Fibroscan® cutoff values applied at baseline were applied after initiation of antiviral therapy the following results were obtained: Within 6 weeks after initiation of treatment fibrosis stage improved by at least one stage in 23/53 (43%) patients, remained stable in 28/53 (53%) and worsened in 2/53 (4%). From the 23 patients classified as F2 at baseline, 11 (48%) were classified as F0/F1 at week 1‐6, 10 (43%) as F2, and 2 (9%) as F3. From the 12 patients classified as F3 at baseline, 3 (25%) were classified as F0/F1 at week 1‐6, 4 (33%) as F2, and 5 (42%) as F3 From the 18 patients with F4 at baseline, 1 (6%) was classified as F0/F1 at week 1‐6, 2 (11%) as F2, 2 (11%) as F3 and 13 (72%) as F4 Decrease of liver stiffness did not correlate with baseline AST (r=0.28) or ALT (r=0.04) levels In our study a marked decrease of liver stiffness was observed within two weeks after initiation of antiviral therapy From a pathophysiologic point of view a clinically significant decrease of liver fibrosis within such a short period of time seems impossible We therefore assume, that the decrease is caused by resolution of the inflammatory activity within the liver Current cut‐off values for assessment of fibrosis stage in patients with chronic hepatitis C by transient elastography were obtained in patients with fibrosis and active inflammation. Therefore, our data clearly indicate that lower cut‐off values for liver stiffness are appropriate for monitoring liver fibrosis after initiation of antiviral therapy.

Disclosures:

Michael Gschwantler ‐ Advisory Committees or Review Panels: Janssen, BMS, Gilead, AbbVie; Grant/Research Support: AbbVie, Gilead; Speaking and Teaching: Janssen, BMS, Gilead, AbbVie

The following people have nothing to disclose: Stephan Moser, Enisa Gutic, Michael Schleicher

Center for Disease Analysis, Louisville, CO

The 69^th World Health Assembly passed a resolution to eliminate viral hepatitis by 2030. Reliable disease burden estimates are required to develop strategies to achieve this goal. The Polaris Observatory was created to gather data and model the change in annual disease burden estimates for HBV, HCV and HDV. Disease burden models were developed for 100 countries to estimate the prevalence of HCV in 2016. The model took into consideration new infections, disease progression, mortality and cured. A Delphi process (using published literature followed by interviews with local experts) was used to gather data for 60 countries. Literature search was used for another 40 countries. The global prevalence was estimated by using regional averages for countries without data. Approximately 70 (56‐90) million individuals were estimated to experience viremic HCV infection. This is lower than 2014 published estimates due to more recent (lower) prevalence estimates in African countries and a large increase in treatment. Lower estimates can also be attributed to an increase in mortality due to liver‐related causes and an aging population. In 2015 alone, approximately 500 thousand individuals were treated and cured. The largest increase in treatment was in the United States (260K treated in 2015) followed by Egypt (190K) and the European Union (135K). Although this increase in treatment is a substantial step towards reducing the global burden of liver related deaths, the current treatment rate is not sufficient to achieve elimination by 2030.

Disclosures:

Sarah Blach ‐ Employment: Center for Disease Analysis

Ivane Gamkrelidze ‐ Employment: Center for Disease Analysis

Jessie Gunter ‐ Employment: Center for Disease Analysis

Helen Nde ‐ Employment: Center for Disease Analysis

Devin M. Razavi‐Shearer ‐ Employment: Center for Disease Analysis

Kathryn L. Razavi‐Shearer ‐ Employment: Center for Disease Analysis

Homie Razavi ‐ Grant/Research Support: Gilead, Abbvie; Management Position: Center for Disease Analysis

The following people have nothing to disclose: Chris Estes, Kimberly Murphy, Ken Pasini, Sarah Robbins, Jonathan D. Schmelzer

¹Internal Medicine Department, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt, Mansoura, Egypt; ²Egyptian Liver Research Institute and Hospital (ELRIAH), Mansoura, Egypt

Background and Aim: Analysis of volatile organic compounds (VOCs) in the exhaled breath can identify markers for alcoholic and nonalcoholic fatty liver disease. The aim of this pilot study was to investigate the utility of C13‐Aminopyrine breath test in the diagnosis of advanced fibrosis (F3‐4) in patients with chronic hepatitis C virus (HCV) infection. Methods: Patients undergoing liver biopsy were recruited. Fibrosis was determined by an experienced pathologist and staged according to METAVIR score. Advanced fibrosis was defined as F3‐4. Exhaled breath and plasma samples were collected within 2 weeks of the biopsy, and Infra‐Red Isotope Analyzer (IRIS) was used to analyze breath samples for C13 aminopyrine. Results: In all, 36 patients were included with a mean age of 41.6±9.4 years, 91.7% were males, and 8 (22.2%) had advanced fibrosis (F3‐F4) IRIS analysis of exhaled breath revealed that patients with advanced fibrosis had significantly lower values of C13‐aminopyrine compared with those without advanced fibrosis at both 30 min and 120 min; P=0.007 and P=0.004 respectively. At 30 min and 120 min, 26 (72.2%) patients and 21(58.3%) patients has levels >3.15 and > 8.25 respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the breath test at 30 min and at 120 min using the new cut‐off values, compared to the standard values, are shown in the table below. The AUROC used for diagnosis of advanced fibrosis by breath test at min 30 and at 120 min were 0.81 (95% CI: 0.647‐0.969; P=0.009) and 0.83 (95% CI: 0.668‐0.984; P=0.005) respectively. CONCLUSION: C13 aminopyrine breath test is a potential biomarker for advanced fibrosis that warrants further validation. The breath test is a good negative test to detect non‐severe fibrosis with the new cut‐off (at 30 min: 3.15, 120 min: 8.25).

Disclosures:

The following people have nothing to disclose: Gamal Shiha, Reham Soliman, Seham Seif, Waleed Samir

¹University of Michigan, Ann Arbor, Ml; ²Veterans Affairs Hospital, Ann Arbor, Ml

Background: Despite advances in therapy, chronic hepatitis C (CHC) remains an important worldwide public health problem. The aim of this study is to externally validate a longitudinal prediction model (Konerman, Hepatology 2015) for risk of adverse clinical outcomes derived from a cohort with advanced CHC among patients (pts) with both early and advanced stage CHC. Methods: Adults with CHC seen in our hepatology clinic between 1/1998‐ 6/2014 were retrospectively analyzed. Pts with hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant (LT), hepatitis B or HIV co‐infection at presentation were excluded. Pts with <3years follow‐up were also excluded. Outcomes included: 1) hepatic decompensation, 2) HCC and 3) LT free survival. Machine learning methods were used to predict outcomes in 1 and 3 years Results: The cohort of 1007 pts had a mean age of 48.9. 61% were male, 80% were white, and 79% had genotype 1. At presentation, 73% were treatment naïve and 31% had cirrhosis. 226 pts developed an outcome over a median follow up of 6.9 years (interquartile range 4.5‐10.5). The area under the receiver operating characteristic curve (AUROC) for 1 and 3 year risk prediction for a composite clinical outcome (decompensation, HCC, LT, liver‐related death) was: 0.78 (95% CI 0.73‐0.83) and 0.76 (95% CI 0.69‐0.81). Model performance was retained when accounting for achievement of sustained virologic response (N=250) and baseline cirrhosis. Models were accurate for assessing transplant free survival but not HCC (Figure) Mean aspartate aminotransferase to platelet ratio index, mean maximum and baseline platelet count, and mean albumin contributed most significantly to the risk predictions Conclusions: Accurate assessments for risk of clinical outcomes among pts with CHC can be obtained using routinely collected longitudinal data. These models retain their accuracy across pts with minimal or no fibrosis at baseline, different treatment exposures and varied genotypes Given the worldwide burden of CHC, our models can convey useful prognostic information to guide intensity of clinical monitoring and urgency of treatment.

Disclosures:

Anna S. Lok ‐ Grant/Research Support: Gilead, BMS

The following people have nothing to disclose: Monica Konerman, Dongxia Lu, Yiwei Zhang, Mary Thomson, Ji Zhu, Aashesh Verma, Nizar Talaat, Peter Higgins, Akbar K. Waljee

¹Public Health Sciences, Loyola University Chicago, Maywood, IL; ²Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL

Background: In the United States (US) major risk factors for acquiring Hepatitis C (HCV) are well known (i. e., intravenous drug users (IDU), blood transfusion prior to HCV screening 1992, HIV infected men who have sex with men). However, in 15‐20% of cases, there are no identifiable risk factors. In the present study we examine the association of sexual risk factors with the risk of HCV infection among adult, non‐HIV infected, non‐IVDU individuals. Methods. NHANES is a population based representative survey of individuals in the US Data from 2005 to 2012 were combined for this study. We exclude: intravenous drug users (IDU), and persons less than 20 years old or older than 68 years; and for the multivariable analysis HIV positive participants Results. The overall N was 15, 850, with an overall anti‐HCV prevalence of 1.2% (95% CI, 0.9% to 1.5%). Peak prevalence estimates was observed among persons 40 to 49 years of age, with a prevalence of 2.3% (1.7%‐2.9%). All sexual risk factors were associated with HCV infection among non‐IVDU individuals. HCV prevalence was 3.1% among non‐IVDU individuals with ≥ 50 sexual partners compared to 0.7% among individuals with 0‐9 partners The HCV prevalence was 2.8% among those with Herpes (HSV), compared to 0.6% among those not infected with HSV. Among individuals with sexual debut ≤ 15, HCV prevalence was 2.6% compared to 0.9% among those with sexual debut > 18 years of age. Further, the prevalence among those both HSV positive AND with sexual debut younger ≤ 15 was 4.1% (2.0‐6.1) compared to 0.3% (0.1‐0.5%) for those who were HSV negative and with older sexual debut at ≥ 18 All multi‐variable analyses examining the association of sexual risk factors with HCV infection controlled for age, gender, education, poverty, ethnicity, marital status, blood transfusion, and drug use (non‐ IVDU). In the multiple variable models, the adjusted OR's for HSV infection compared to no HSV infection was 2.3(1.1‐4.8). Lifetime partners > 10 had an OR's of 2.2(1.2‐4.0) compared to 0‐9 lifetime partners. Finally, sexual debut<15 carried an OR of 5.3(2.9‐9.8) compared to sexual debut≥18 years of age. Among individuals both HSV positive and with early sexual debut (<15 years) the OR (95% CI) was 5.2(2.0‐13.4) compared to those without HSV and later sexual debut. Conclusion. Examining risk factors among a non‐IVDU population, non‐HIV infected population using population based US data, we identified numerous sexual risk factors to be associated with HCV infection in both uni‐and multi‐variable analyses. Such data suggests that among individuals engaging in higher risk sexual behaviors, HCV may be transmitted through sexual activity.

Disclosures:

The following people have nothing to disclose: Nallely Mora, William H. Adams, Stephanie Kliethermes, Lara R. Dugas, Jennifer E. Layden

¹Hospital General Universitario Gregorio Marañón, Madrid, Spain; ²Centro Nacional de Microbiología. ISCIII, Majadahonga, Spain; ³Fundación Investigacion Biomédica Gregorio Marañón, Madrid, Spain

Mitochondria provide energy to eukaryotic cells via oxidative phosphorylation and regulate cellular survival via control of apoptosis. Mutations in the mitochondrial DNA (mtDNA) are related to many human diseases. Some of these mtDNA mutations have been acquired throughout human history by natural selection allowing subdividing the human population into a number of discrete mitochondrial clades or haplogroups defined on the basis of specific mtDNA polymorphisms. European mtDNA haplogroups have found to influence liver fibrosis progression in HIV/HCV‐coinfected patients (AIDS 2011; 25: 1619‐26). The aim of our study was to assess the relationship between mtDNA haplogroups and liver‐related events (LRE) in HIV/HCV‐coinfected patients. Methods: We studied clinical characteristics and outcomes of 243 HIV/HCV‐coinfected patients with a baseline liver biopsy and simultaneous blood and serum samples who were followed for a median of 93 months (7.75 years). The primary endpoint was the occurrence of LRE defined as decompensation or hepatocellular carcinoma, whichever occurred first. The mtDNA genotyping was performed by Sequenom's MassARRAY platform. Univariate and multivariate Fine and Gray proportional hazards regression ‐ taking into account death as the competing risk ‐ were used to test the association between mtDNA haplogroups and LRE. Variables for adjustment were alcohol intake, FIB‐4 score and sustained viral response (SVR). Results: During follow‐up, 175 patients were treated with interferon and ribavirin and 90 achieved SVR. A total of 18 patients had LRE, and 11 patients died. Out of 243 patients, 109 (47.8%) patients had mtDNA haplogroup H, and 3 (2.75%) had a LRE; whereas 25 (10.3%) patients were haplogroup T and 5 (20%) had a LRE Haplogroup H was associated with a lower hazard of LRE in univariate analysis [subhazard ratio (SHR)=0.26 (95%CI=0.08; 0.91); P=0.035] and multivariate analysis [adjusted SHR (aSHR)=0.34 (95%CI=0.10; 1.19); P=0.092]; whereas haplogroup T was associated with a significant higher hazard of LRE in univariate analysis [SHR=3.31 (95%CI=1.03; 10.62); P=0.045] and multivariate analysis [aSHR=4.18 (95%CI=1.35; 12.92); P=0.013]. Conclusions: mtDNA haplogroup T was associated with an increased hazard of LRE, whereas haplogroup H was associated with a reduced hazard of LRE. These results suggest that mtDNA haplogroups are host‐related factors that influence the natural history of chronic hepatitis C in patients with HIV infection.

Disclosures:

The following people have nothing to disclose: Salvador Resino, Teresa Aldámiz‐Echevarría, María A Jiménez‐Sousa, Pilar Miralles, Luz M Medrano, Ana Carrero, Cristina Diez, Leire Pérez‐Latorre, José M. Bellon, Juan Berenguer

¹BC Centre for Disease Control, Vancouver, BC, Canada; ²University of British Columbia, Vancouver, BC, Canada; ³British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada

Background: About 25% of individuals infected with hepatitis C virus (HCV) spontaneously clear their infection but can be at risk of reinfection. Data on spontaneous clearance of HCV after reinfection (re‐clearance), particularly reinfections with a heterologous genotype, in humans are very limited. We examined HCV re‐clearance in a large population‐based cohort in British Columbia, Canada. Methods: For this analysis, we used data from the BC Hepatitis Testers Cohort that includes all individual tested for HCV between 1990 and 2013 linked with data on their medical visits, hospitalizations, and prescription drugs We identified people with HCV reinfection who underwent follow up HCV‐RNA testing (n=958; 865 cleared their first infection spontaneously while 93 achieved sustained virologic response [SVR] through treatment) to examine HCV re‐clearance Multivariable Cox proportional hazard model was used to identify potential predictors of re‐clearance Results: About half (48%, n=460) the participants spontaneously cleared the reinfection with an incidence rate of 16.92 (95% confidence interval [CI]: 15.41‐18.53) per 100 person‐years (PY). Both the proportion and the incidence rate of re‐clearance (per 100 PY) in those who spontaneously cleared their first infection (proportion: 50.5%; rate: 17.8, 95%CI: 16.17‐19.55) were more than twice that in those who achieved SVR through treatment (proportion: 24.7%; rate: 8.71, 95% CI: 5.52‐13.07). In adjusted analysis, the likelihood of HCV re‐clearance was higher among those who spontaneously cleared their first infection compared to those who achieved SVR (adjusted hazard ratio [aHR]: 1.93, 95% CI: 1.24‐2.99), and lower if reinfected with a heterologous HCV genotype (aHR: 0.70, 95% CI: 0.47‐1.03) Conclusion: Ability to spontaneously clear first infection markedly increases the likelihood of clearing subsequent infections, but does not confer protection against a heterologous virus.

Disclosures:

Mel Krajden ‐ Grant/Research Support: Roche, Merck, Siemens, Boerhinger Ingelheim, Hologic

The following people have nothing to disclose: Nazrul Islam, Jeannie Shoveller, Paul Gustafson, Mark Gilbert, Jason Wong, Mark Tyndall, Naveed Z. Janjua

¹Inserm, IAME, UMR1137, Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France; ²Univ. Lille, Inserm, CHU Lille, U995 ‐ LIRIC ‐ Lille Inflammation Research International Center, Lille, France; ³Département des Maladies Infectieuses, Santé publique France, Saint Maurice, France; ⁴Service Santé Publique, Hôpital Henri Mondor, Créteil, France; ⁵Service des Maladies de l'Appareil Digestif et de la Nutrition, Hôpital Huriez, CHRU Lille, Lille, France; ⁶Inserm U955, Hôpital Henri‐Mondor, Créteil, France; ⁷Service de maladies Infectieuses et tropicales, Hôpital Bichat Claude Bernard, Paris, France

In France, recommendations for Hepatitis C Virus (HCV) screening still target only people at high risk of infection, and 40% of infected‐persons remain unaware of their status. In the context of highly effective and tolerable therapies, that will be recommended for all patients in a near future, a reassessment of HCV screening strategies is needed. A cost‐effectiveness study was conducted in the French general population, aged 18 to 80 years, undiagnosed for chronic hepatitis C (CHC) A Markov model simulated life expectancy in discounted quality adjusted life years (QALYs), direct lifetime discounted costs and incremental cost‐effectiveness ratio (ICER) for different strategies, from 2016 until death: S1=current strategy targeting the at risk population (63% of the study population) that effectively screened 10‐19% of at risk population, and 4‐18% of those not at risk; S2=S1 and all men between 18 and 60 years; S3=S1 and all people between 40 and 60 years; S4=S1 and all people between 40 and 80 years; S5=all people between 18 and 80 years We assumed that S2 to S5 reached 100% of the targeted age‐cohort population. Once CHC diagnosed, treatment was initiated regardless of fibrosis either with the least or the most expensive treatment combination We relied on published literature and on a national prevalence survey Characteristics of undiagnosed persons in terms of fibrosis according to gender, age and alcohol consumption, and time to screening, were obtained from a previously published mathematical model Whatever the treatment combination (Table), when we considered treatment for all, compared to the current screening strategy, adding all men aged 18‐60 years was associated with the lowest ICER (27,600‐31,900€/QALY). Targeting all people aged 40‐80 was more effective than targeting all men aged 18‐60 years and remained cost‐effective (39,100‐44,800€/QALY). Universal screening was even more effective than targeting all people 40‐80 and remained cost‐effective (40,300‐46,300€/QALY) In France, although universal screening is associated with the highest costs, it is the most effective strategy and is cost‐effective when treatment is initiated regardless of fibrosis.

Table. Cost‐effectiveness analysis considering either the least or the most expensive treatment combination

*Weakly dominated strategy: higher ICER than that of a more effective alternative strategy

Disclosures:

Sylvie Deuffic‐Burban ‐ Consulting: MSD, Abbvie, BMS, Abbott, Janssen Pharmaceuticals, Gilead, HEVA, Public Health expertise; Grant/Research Support: Janssen Pharmaceuticals, MSD, ARHEL; Speaking and Teaching: Janssen, Gilead, BMS

Françoise Roudot‐Thoraval ‐ Advisory Committees or Review Panels: Roche, Gilead; Speaking and Teaching: Roche, AbbVie, Gilead, BMS, Janssen

Philippe Mathurin ‐ Board Membership: MSD, Janssen‐Cilag, BMS, Gilead, Abvie, Verlyx; Consulting: Roche, Bayer

Daniel Dhumeaux ‐ Stock Shareholder: Janssen‐Cilag

Yazdan Yazdanpanah ‐ Board Membership: Abbvie, BMS, GILEAD, MSD, ROCHE, Johnson&Johnson, ViiVHealthcare, Pfizer, Janssen; Consulting: AbbVie, BMS, GILEAD, MSD, Roche, Johnson&Johnson, Viiv Healthcare, Pfizer, Janssen

The following people have nothing to disclose: Alexandre Huneau, Adeline Verleene, Cécile Brouard, Josiane Pillonel, Yann Le Strat, Sabrina Cossais, Valerie Canva‐Delcambre

¹BC Centre for Disease Control, Vancouver, BC, Canada; ²University of British Columbia, Vancouver, BC, Canada; ³British Columbia Cancer Agency, Vancouver, BC, Canada

Background: The risk of hepatocellular carcinoma (HCC) in people who spontaneously clear HCV infection (SC), those who achieve treatment‐based SVR (RxSVR), those who fail treatment (RxFail) and those with untreated chronic HCV (NoRx) is not well established. We evaluated the HCC risk in these patient groups using the BC Hepatitis Testers Cohort (BC‐HTC). Methods: The BC‐HTC includes ∼1.5 million individuals tested for HCV, HIV or reported as a case of HBV, HCV, HIV or active TB between 1990‐2013, linked with medical visits, hospitalizations, cancers, prescription drugs and mortality. Cumulative incidence function and multivariable Cox proportional hazard models were used to examine HCC risk in the four HCV groups (SC, RxSVR, RxFail, NoRx). Results: Of 46,046 eligible individuals: 12,493 were SC; 9,140 were treated of whom 5,320 (58%) were RxSVR and 3,820 (43%) were RxFail; 24,413 had chronic HCV and NoRx. The four groups were followed for a median (IQR) of 11 years: SC 10.6 (2.0‐15.0); RxSVR 11.2 (7.0‐14.9); RxFail 11.7 (7.915.0); NoRx 10.8 (6.3‐17.0). The RxFail group had a higher level of cirrhosis (23% vs <9%) and diabetes (13% vs <7%) than other groups. The annual HCC incidence rate per 1,000 person‐yr (PY) was 0.26 (HCC/PY=34/129,382) for SC; 1.19 (35/29,304) for RxSVR; 7.7 (170/ 22,169) for RxFail; and 1.24 (381/307,828) for NoRx. The HCC incidence rate was higher among those with cirrhosis in all groups. In the multivariable model, compared to NoRx, SC (hazard ratio (HR) =0.24, 95%CI:0.17‐0.35)) and RxSVR (HR=0.59, 95%CI:0.42‐ 0.84) were associated with reduced HCC risk, while RxFail (HR=3.54, 95%CI:2.93‐4.28) had a higher HCC risk. As expected, cirrhosis (HR=3.25, 95%CI:2.23‐4.75), older age (50‐59 yr: HR=4.35, 95%CI:3.58‐5.28; 60+ yr: HR=9.16, 95%CI:7.27‐11.54 compared to ≤49 yr), male sex (HR=2.18, 95%CI:1.79‐2.66), genotype 3 vs. 1 infection (HR=1.64, 95%CI:1.34‐2.02), and problematic alcohol use (HR=1.48, 95%CI:1.20‐1.83) increased the adjusted HCC risk. Conclusions: As expected, the HCC risk for SC was low. The RxFail group had the highest HCC risk, likely reflecting a poorer prognostic profile at treatment initiation This highlights the limited HCC prevention benefits of treating later stage disease with older interferon‐based regimens even if SVR is achieved. The higher HCC risk for RxSVR compared to SC suggests that earlier HCV treatment will be required to achieve the same risk reduction observed for SC.

Disclosures:

Mel Krajden ‐ Grant/Research Support: Roche, Merck, Siemens, Boerhinger Ingelheim, Hologic

The following people have nothing to disclose: Mark Tyndall, Mei Y. Chong, Darrel Cook, Jason Wong, Margot E. Kuo, Hasina Samji, Zahid Butt, Amanda Yu, Maria Alvarez, Ryan Woods, Naveed Z. Janjua

¹Department of Internal Medicine and Clinical Immunology, AP‐HP, Groupe Hospitalier Pitié‐Salpêtrière, Paris, France; ²Inflammation‐Immuno‐ pathology‐Biotherapy Department (DHU i2B), Sorbonne University, UMPC Univ Paris 06, UMR 7211, Paris, France; ³CEMKA, Paris, France; ⁴Department of Medicine, Inova Fairfax Hospital, Center for Liver Diseases, Falls Church, VA; ⁵Inova Health System, Betty and Guy Beatty Center for Integrated Research, Falls Church, VA

Background Hepatitis C virus (HCV) infection is a systemic disease which is associated with both hepatic and extrahepatic manifestations (EHM). The disease burden associated with the hepatic manifestation of HCV is well documented. However, the economic impact of EHM of HCV outside the United States remains unknown. Objective To estimate the annual direct medical costs associated with EHM of HCV in France. Methods A previously validated economic model was used to estimate the annual direct medical cost associated with EHM of HCV. Prevalence of nine EHM (mixed type 2 cryoglobulinemia vasculitis, chronic kidney disease, type 2 diabetes mellitus [DM], lymphoma, lichen planus, Sjogren's syndrome, porphyria cutanea tarda, rheumatoid‐like arthritis, and depression) were obtained from a recent systematic review and meta‐analysis (Younossi et al. 2016). Per‐patient‐per‐year (PPPY) inpatient, outpatient and medication costs to treat each of these EHM in France was obtained from the literature, from the French medico‐administrative database (PMSI) or expert opinion if unavailable otherwise Prescription drug costs were taken from the VIDAL website. All costs were adjusted to 2015 euros (€). The overall national direct medical costs associated with EHM of HCV were calculated by multiplying the total PPPY costs of each EHM by the respective prevalence rates, and then by the size of the HCV‐infected population in France (INSEE; Corinne Pioch 2016). Sensitivity analysis was performed considering the 95% Confidence intervals reported in Younossi et al.Results In 2014, 192,700 individuals were estimated to be infected with HCV in France. The mean average PPPY cost of EHM was 1,354.52€. The total annual direct medical cost associated with the care of patients with the EHM of HCV in France was estimated to be 261,016,256€. The sensitivity analyses suggested a range of 108.6 to 354.9 million euros in total cost associated with the extrahepatic manifestation of HCV. Conclusion Extrahepatic manifestations of HCV are quite costly and substantially add to the overall economic burden of HCV infection.

Disclosures:

Patrice P. Cacoub ‐ Advisory Committees or Review Panels: gilead, abbvie; Grant/Research Support: msd, bms; Speaking and Teaching: janssen

Antoine Lafuma ‐ Grant/Research Support: Genomic Health, GSK, Pierre Fabre M√©dicament, UCB, BMS, Bayer, Gilead, Biogen, Gedeon Richter, Urgo, Sanofi, Diaxonhit, Janssen, Insmed, CSL Berhing, Eisai, MSD

The following people have nothing to disclose: Mathieu Vautier, Anne Claire Desbois, Marianne Doz, Zobair M. Younossi

¹Medicine, Emory University, Atlanta, GA; ²Epidemiology and Biostatistics, Georgia State University, Atlanta, GA

Purpose: To examine 2‐year outcomes along the HCV Care Cascade among a population of over 5,000 baby boomers screened for HCV infection from 2012‐2014 in an academic, primary care setting targeting underserved individuals Methods: The TILT‐C program, funded by the CDC, implemented baby boomer screening and linkage to care from 2012‐2014 at the Grady Memorial Hospital Primary Care Center (Atlanta, GA, USA). Twenty months after the completion of the screening program, we evaluated records of the 412 patients who screened positive for HCV antibodies. Outcomes reported for the subset with chronic HCV infection included type of initial linkage to care, number of follow‐up visits, number referred for antiviral treatment, reasons for non‐treatment, and numbers who achieved rapid virologic response (RVR), end of treatment response (ETR) and sustained virologic response 12 weeks after completion of therapy (SVR12). Results: In a birth cohort population that was 92.5% African American and 53% uninsured, 412 (7.9%) of 5,239 patients screened had HCV antibodies. HCV RNA testing was completed for 92% of the antibody‐positive patients, and 264 (69%) were viremic. 96% of viremic patients had an initial linkage to care visit; 43% at the onsite, primary care‐based HCV clinic, 6% at the infectious disease clinic, and 47% at the primary care clinic Subsequently, 75% of patients attended a second specialty visit, 55% a third visit, 30% a fourth, and 13% a fifth Eighty‐two patients were referred for direct acting antiviral (DAA) treatment Reasons for non‐treatment included lack of advanced fibrosis (30%), lost to follow‐up (29%), awaiting newer medications (13%), and substance abuse (8%). Among the 42 patients with results available who initiated DAA therapy, 29 of 42 (69%) achieved RVR, 37 of 38 (97%) achieved ETR, and 25 of 27 (93%) achieved SVR12. Conclusions: Our results show that following a highly successful HCV screening and linkage to care program, there remains significant drop off along the later stages of the HCV Care Cascade This resulted in sub‐optimal numbers of patients initiating DAA therapy, despite the fact that excellent outcomes were achieved once patients initiated therapy Our finding that lost to follow up was a significant contributor to non‐treatment suggests that interventions focused on maintaining patients in care (patient navigators, case managers) could improve treatment uptake in this underserved population with high HCV prevalence.

Disclosures:

Lesley Miller ‐ Advisory Committees or Review Panels: Bristol Myers Squibb; Grant/Research Support: Gilead sciences

Shelly‐Ann Fluker ‐ Grant/Research Support: Gilead Sciences

The following people have nothing to disclose: Cameron B Body, Brandi Park, Wynnetta Wimberley, Ike S. Okosun

Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY

Background and aim: New treatments allow an increasing number of patients to be cured of chronic hepatitis C virus (HCV) infection Anecdotally, many patients have complained that a sustained virologic response (SVR) was accompanied by weight gain The aim of this study was to analyze weight changes and factors associated with weight changes in patients cured of HCV through treatment with sofosbuvir (SOF)/ledipasvir (LDV). Methods: Data were collected on patients treated with SOF/LDV who achieved an SVR, and had body weight measurements recorded at baseline (within eight weeks of the start of treatment) and within four weeks of SVR. Patients without documented weights, who were on diuretics (furosemide and spironolactone), had significant ascites, and/or had co‐morbidities likely to cause weight changes (e. g., malignancies) were excluded Cirrhosis was determined by diagnostic codes Diabetes was defined as hemoglobin A1c ≥ 6.5%. Obesity was a body mass index (BMI) ≥ 30.0. Weight changes were analyzed by paired t‐tests for two intervals: baseline to SVR, and baseline to end of follow up (up to 520 days from baseline) Results: Of the 1.67 patients, 93 patients (56%) were male, mean age was 60 ± 11 yr. The mean weight change baseline to SVR was +2.6 ± 7.8 pounds (lb), (p < 0.01). Baseline to SVR, 94 patients (64%) gained weight, 43 (29%) lost weight, and 11 (7%) remained within 1 lb of baseline The mean gain was +7 ± 5.3 lb, and the mean loss was −6.5 ± 4.9 lb Sixty patients (41%) gained ≥ 5 lb, 23 (16%) gained ≥ 10 lb, and 11 (7%) lost ≥ 10 lb. Diabetic patients (n = 24) gained significantly more weight, 5.8 ± 7.2 lb, than non‐diabetics (n = 124), 1.9 ± 7.8 lb (p = 0.03). There was no statistically significant difference in weight change between males and females (p = 0.38), patients with and without cirrhosis (p =0.42), patients with and without obesity (p =0.90), patients with treatment > of less than 12 weeks (p = 0.29) Pre‐treatment albumin, total cholesterol, LDL, HDL, and triglycerides did not differ significantly between patients who gained weight and those who lost weight. Among 103 patients with a second post‐SVR weight measurement, the mean change was 3.7 ± 9.0 lb, (p <0.01). Conclusion: 64% of patients who achieved an SVR with SOF/ LDV treatment gained weight The gain for the entire group was modest, 2.6 lb, but was greater for diabetics, 5.8 lb Weight increases continued during follow up To prevent excessive weight gain, patients receiving HCV treatment, especially those with diabetes, may benefit from advice about diet and exercise (DA 031095, DK 090317).

Disclosures:

Kian Bichoupan ‐ Consulting: Janssen, Gilead

Andrea D Branch ‐ Grant/Research Support: Gilead, Galmed

The following people have nothing to disclose: Adiba Azad, Sweta Chekuri, Thomas Schiano

Keio University School of Medicine, Tokyo, Japan

Background and Aims: Interferon (IFN)‐free direct antiviral agents (DAAs) effectively eradicate hepatitis C viruses (HCV) and rapidly improve liver residual functions. However, whether IFN‐free DAAs prevent HCC primarily or secondarily is still unknown Chronic hepatitis C (CHC) causes dysregulation of iron metabolism, which leads to moderate iron overload featured as hyperferritinemia. Iron overload is also suspected to be one of the factors favoring HCV‐related hepatocellular carcinoma (HCC). However, whether IFN‐free DAAs normalize HCV‐related hyperferritinemia, and may ferritin be a possible predictive factor for HCC undergoing DAAs, are not yet elucidated. Methods: With the commitment of institutional review board and prior informed consents, 70 genotype 1 CHC patients undergoing IFN‐free DAAs (54 with daclatasvir and asunaprevir; 18 with sofosbuvir and ledipasvir) were recruited, and laboratory data at day 0 (pre) and at the end of treatment (EOT) were analyzed. Patients with active bleeding, iron supplementation, end‐stage renal disease, and women before menopause were excluded in this analysis. For HCC surveillance, patients were followed according to guidelines by AASLD/IDSA. Any HCC identified after EOT within 6 months was defined as early emergence. Results: Eight cases of early post‐treatment HCC emergence were noticed (11.4%). At EOT, serum ferritin decreased significantly (199±198 IU/l vs. 91 ± 80 IU/l, p<0.0001), and this significant decrease was also noticed when adjusted by gender or by age. The change rate of serum ferritin (Aferritin%, compared to pre‐treatment values) correlated significantly to the change rates of ALT (p< 0.0001), type 4 collagen 7s (p<0.0001), LDL (p= 0.01), albumin (p= 0.02), and Y‐globulin (p= 0.03), and tended to correlate to the change rate of alpha‐fetoprotein (AFP, p= 0.06) Δferritin% of cases with early post‐treatment emergence of HCC was significantly lower (−31.3±30% vs. −46.5±30%, p= 0.03). In multivariate analysis, along with HCC past history, Aferritin% (p= 0.04; AUC= 0.74 at cut‐off value of 49% reduction) was a significant predictive factor of early post‐DAA emergence of HCC Conclusion: Hyperferritinemia was normalized rapidly after IFN‐free DAA, in accordance to HCV eradication and improvements in clinical markers for hepatic injury, hepatic stellate cell activity, lipid and protein metabolism Aferritin% is one of the independent and significant predictive factors of early HCC emergence after IFN‐free DAAs. Since obesity or excessive alcoholic intake may also cause hyperferritinemia, serum ferritin might be a useful collective predictive marker of HCC for patients who achieve SVR with IFN‐free DAAs.

Disclosures:

The following people have nothing to disclose: Po‐sung Chu, Nobuhiro Nakamoto, Aya Ugamura, Hirotoshi Ebinuma, Hidetsugu Saito, Takanori Kanai

University of Florence, Florence, Italy

HCV infects about 170 million of subjects worldwide. The virus has a high propensity to persist in the host, leading to cirrhosis and liver cancer. Metabolomics is the study of metabolic changes in biological systems and may identify specific profiles associated with subtle alterations induced by diseases. Few studies are available on metabolitic changes in liver injuries, and since none of which was focused on HCV‐infected patients before and after reaching a SVR following treatment with direct acting antivirals (DAAs), the aim of this study was to perform a serum metabolomics analysis in this setting Sera were collected from 52 HCV patients (18 men, mean age 65±9,7) successfully undergoing different IFN‐free DAA regimens, before therapy (baseline) and at post‐treatment week 12 (SVR12). HCV genotype was 1a/1b in 70%, 2a/2c in 23%, 3 in 4.7% and 4 in 2.3%. METAVIR score indicated F3‐F4 score in 55% of patients, the remaining 45% had F0‐F2 We also analyzed a small group of 12 sera from healthy subjects in order to localize them in the PLS plot respect to baseline and SVR12 as a preliminary negative control for both groups. Samples were analyzed using proton nuclear magnetic resonance spectroscopy (¹H‐NMR). Partial Least Squares (PLS) and the canonical analysis (CA) were applied, demonstrating a significant pair‐wise discrimination (96% of accuracy) for the two time‐points of each patient and highlighting a metabolic shift Several metabolites with unequivocal assignment (i e amino acids, organic acids, creatine, creatinine, lactate and choline) differed comparing baseline with SVR12. Baseline featured higher level of formate and acetate (p<0.05) and methionine was higher in SVR12 (p<0.05). Preliminary analysis revealed also a progressive nearing of SVR12 to the healthy fingerprint. The serum metabolomic analysis of pre‐ and post‐treatment samples showed remarkable profile changes from baseline to SVR12. We found variations, with opposite directions, in formate (produced in adults only by hepatocytes) and methionine. These metabolites take part in biochemical ways (i e glucose metabolism) also involving acetate and other amino acids, going through the synthesis of folates These alterations could be implied in the metabolic impairment previously observed in chronically infected HCV‐patients. Also, since methionine is the major source of methyl groups, an understanding of its variation, could reveal important dysfunctions in liver essential pathways requiring methylation (i e epigenetic regulation of DNA) in HCV‐related chronic infection.

Disclosures:

The following people have nothing to disclose: Giorgia Ceccotti, Gaia Meoni, Leonardo Tenori, Laura Gragnani, Elisa Fognani, Elena Gianni, Claudio Luchinat, Anna Linda Zignego

¹Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; ²General Internal Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; ³Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY

Background and Aims: Primary care based models of HCV care have been successfully established although widespread adoption has been limited. There is an urgent need to scale up global training of providers for HCV. The aim of this study is to develop and operationalize HepCure (hepcure. org), a web‐ based application (app) offering three components: An open access toolkit (a dashboard) that enhances providers' ability to deliver guideline‐based HCV care; a linked patient app that provides education, medication reminders, and a platform for tracking adherence and symptoms; and a tele‐education platform for medical providers. Methods: The HepCure app is a collaboration among an academic, tertiary care medical center, the New York State (NYS) Department of Health (DOH), and community health centers in NYS. The HepCure platform captures United States Centers for Medicaid and Medicare HCV quality indicators for population health management. National HCV treatment guidance was used to provide decision support algorithms Patient data is de‐identified when cases are submitted by providers for discussion at weekly tele‐education sessions with experts. Results: The HepCure Provider Dashboard (http://providers.hepcure.org) was launched in November 2014. Weekly tele‐education sessions have been conducted since February 2015 (n=57) and each session has been archived with open access There have been a total of 322 unique attendees and weekly sessions have been attended by a mean of 22 ± 9 attendees a week. The patient mobile app was launched in November 2015 to increase patient engagement and has had 546 downloads through May 2016. The primary barrier to adoption has been lack of deep integration into existing electronic health records (EHRs). HepCure is currently working with the NYS DOH to integrate HepCure into Epic and EHRs used by over 80% of community health centers in NYS. In addition, the NYS DOH HCV quality indicators (eHepQual) will be integrated into HepCure allowing for direct reporting. Conclusions: The HepCure platform brings HCV infected patients, primary care providers, and expert hepatologists together to increase treatment capacity and patient engagement with the goal of improving health outcomes The initial implementation phase has led to the recommendation for a series of enhancements including EHR integration and creating capacity for local experts to provide case based tele‐education through a hub and spoke model. These upgrades are in process along with research to evaluate the outcomes of providers and patients using HepCure. Implementation of HepCure in resource limited settings without EHRs is also being explored.

Disclosures:

Jeffrey J. Weiss ‐ Consulting: AbbVie Inc.

The following people have nothing to disclose: Ponni V. Perumalswami, Trang Vu, Brooke Wyatt, Korin Parrella, Jason Rogers

¹Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; ²Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY

Background and aim: Amino acid mutations at positions 70 and 91 of HCV core protein are associated with an increased risk of hepatocellular carcinoma (HCC) in Asian patients infected with genotype‐lb HCV. For the first time, in this study, we evaluated the prognostic significance of these mutations in a United States population. Methods: The HCV quasispecies in baseline serum samples of 90 patients with chronic genotype‐lb HCV infection enrolled in the HALT‐C trial were investigated using MiSeq deep sequencing. The relationship between the percentage of the quasispecies with a mutation at position 70 and/ or 91 and the incidence of HCC was evaluated by receiver operating characteristic (ROC), Kaplan‐Meier and multivariable Cox regression analyses. Results: In ROC analysis, quasispecies percentage cut‐points ≥42% of non‐arginine at position 70 (non‐R⁷⁰) or ≥98.5% of non‐leucine at position 91 (non‐L⁹¹) had optimal sensitivity at discerning higher or lower HCC risk. At baseline, the quasispecies of 88.5% (23/26) of the patients who later developed HCC (median follow‐up, 4.4 years; range, 0.4‐8.5) had ≥ 42% non‐R⁷⁰ whereas only 68.8% (44/64) of matched controls who remained HCC‐free (median follow‐up, 7 years; range, 2.7‐8.6) had ≥ 42% non‐R⁷⁰ (P=0.06) (Fisher's exact probability test). The baseline quasispecies of 30.8% (8/26) of patients who developed HCC had ≥ 98.5% non‐L⁹¹ whereas 54.7% (35/64) of matched controls had ≥ 98.5% non‐L⁹¹ (P=0.06). By Kaplan‐Meier analysis, HCC incidence was higher among patients with baseline non‐R⁷⁰ ≥ 42%, but the difference was not significant (P=0.08), while it was significantly lower among patients with baseline non‐L⁹¹ > 98.5% (P=0.01) Additionally, in a Cox regression model, increased HCC risk was associated with the presence of non‐R⁷⁰ > 42% quasispecies at baseline [hazzard ratio (HR)=3.83, 95% confidence interval (CI) = 1.02‐14.3; P=0.04], higher ast/alt ratio (HR=4.08, 95% CI=1.24‐13.47; P=0.02), and higher alkaline phosphatase (HR=1.01, 95% CI=1.0‐1.02; P=<0.001). Greater numbers of white blood cells were associated with reduced HCC risk (HR=0.64, 95% CI =0.45‐0.89; P=0.01). Conclusion: This pilot study of United States patients adds to previous evidence that HCV core protein mutations associate with HCC risk and indicates the potential utility of HCV quasispecies analysis as a non‐invasive biomarker of HCC risk.

Disclosures:

Andrea D. Branch ‐ Grant/Research Support: Gilead, Galmed

The following people have nothing to disclose: Ahmed M. Elshamy, Matthew

Pendleton, Francis J. Eng, Erin H. Doyle, Ali Bashir

¹Gastroenterology and Hepatology, Alameda Health System ‐ Highland Hospital, Oakland, CA; ²Medicine, Alameda Health System ‐ Highland Hospital, Oakland, CA

Background: Successful eradication of chronic hepatitis C virus (HCV) relies on effective screening programs for early detection and linkage to care. However, awareness of HCV screening guidelines may be lacking, especially among urban safety‐net populations with a high prevalence of socioeconomically disadvantaged non‐English speaking minorities. Aim: To evaluate rates of HCV screening and HCV awareness among patients at high risk for chronic HCV at a diverse safety‐net hospital Methods: A prospective cohort study of consecutive adults undergoing outpatient endoscopy from July 2015‐March 2016 evaluated HCV screening rates among high risk patients (based on U.S. Preventative Services Task Force guidelines), with focus on birth cohort (1945‐1965) and risk‐based (history of drug use, incarceration, blood transfusion prior to 1992) factors. Awareness of prior HCV results and rates of accepting HCV testing were evaluated with chi‐square testing and multivariate logistic regression. Results: Among 869 patients, 65.5% (n=569) were high risk for chronic HCV (51.3% male, 57.8% 1945‐1965 birth cohort, 4.5% history of drug use, 6.2% history of incarceration, 5.8% blood transfusion, 9.8% HIV). Among this cohort, 30.6% received prior HCV testing, among which 36.0% were aware of test results. HCV positive patients were more likely than HCV negative patients to be aware of results (90.0% vs. 27.7%, p<0.001). Among high risk patients offered HCV testing, 83.9% accepted. Compared to non‐Hispanic whites (64.0%), blacks (80.6%), Asians (89.6%), and Hispanics (93.7%) were more likely to accept testing, p<0.001. Non‐English speaking patients were more likely to accept testing (91.0% vs. 77.5%, p<0.001). Patients born in 1945‐1965 were less likely to accept testing (82.6% vs. 91.9%, p=0.06). On multivariate regression, blacks, Asians, and Hispanics were all significantly more likely to accept HCV testing compared to non‐Hispanic whites (Table). Conclusion: Among adults presenting for outpatient endoscopy at an urban safety‐net hospital, 65.4% were high risk for HCV, of which only 30.6% received prior testing Of those that received prior testing, only 36% were aware of results. Lower rates of test acceptance among the 1945‐1965 birth cohort is concerning given higher risks among this group.

Predictors of HCV Testing Acceptance

Disclosures:

Robert J. Wong ‐ Advisory Committees or Review Panels: Gilead; Grant/ Research Support: Gilead

The following people have nothing to disclose: Brendan Campbell, Yael Bogler, Rachel Baden, Taft Bhuket, Benny Liu

Epidemiology, Gilead Science, Inc, Foster City, CA

BACKGROUND: The relationship between chronic kidney disease and hepatitis C virus (HCV) infection is well described, but less is known about acute kidney injury (AKI) in the HCV‐in‐ fected population. In addition, the direct‐acting antiviral sofos‐ buvir (SOF) is now widely used in the treatment of HCV. The objective of this cohort study was to characterize rates of AKI in HCV‐infected patients versus patients without HCV, and to examine these rates during exposure to SOF‐containing and non‐SOF containing treatment regimens. METHODS: 173,677 adult patients with evidence of HCV infection were identified from a large US administrative medical claims database (claims incurred from January 1,2010 to March 31,2015). Data from these patients were compared with those from a random 1% sample of adult patients without evidence of HCV infection (N=529,265) from the same database. Validated administrative claim codes were used to determine first diagnosis of AKI All included patients had at least 6 months of continuous enrollment in their medical plan prior to cohort entry and no prior AKI‐related claims. Absolute rates and their corresponding exact Poisson 95% confidence intervals (CIs) were determined for each group, and adjusted incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS: Among identified HCV patients, the absolute AKI rate was 2.91 per 100 person‐years (PY; CI: 2.85‐2.98) versus 0.40 per 100 PY (CI: 0.39‐0.41) in the non‐HCV population. AKI rates were higher among patients with concomitant cirrhosis and with concomitant end‐stage liver disease or liver transplant (9.27 and 21.63 per 100 PY, respectively) After adjustment for age, sex, and baseline covariates including renal insufficiency and cirrhosis, HCV infection was found to be associated with an approximate 4‐fold increase in risk of AKI (IRR=3.89, CI: 3. 404.45, p<0.0001). Among HCV‐infected patients receiving treatment, the absolute AKI rate during exposure to SOF‐con‐ taining regimens was 4.32 per 100 PY (CI: 3.51‐5.25), while the rate during exposure to alternative treatments was 3.62 per 100 PY (CI: 3.15‐4.14). After adjusting for age, sex, and baseline covariates including renal insufficiency and cirrhosis, exposure to a SOF‐containing regimen was associated with a non‐significant reduced risk of treatment‐emergent AKI events (IRR=0.81, CI: 0.63‐1.04). CONCLUSIONS: The results of this real‐world observational study indicate that HCV infection is independently associated with increased risk of AKI, and that there is no independent association between exposure to SOF and risk of treatment‐emergent AKI These results should be confirmed in future investigations.

Disclosures:

Laura Telep ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences Andrea Brown ‐ Employment: Gilead Sciences, Inc

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Anand P Chokkalingam ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan

Background and Aims: Histological hepatic fibrosis is an important predictive factor for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC). However, owing to the invasive nature of liver biopsy, several alternative fibrosis markers have been proposed. FIB‐4, an index that combines standard biochemical values and age, is recognized as not only a simple and reliable alternative to liver biopsy for assessing hepatic fibrosis, but also a useful predictive marker for HCC development. Recent advances in antiviral treatment have improved the rate of sustained virological response (SVR) in patients with CHC. However, the risk of HCC development persists even in patients who achieve SVR. Achievement of SVR results in alteration of standard biochemical values in most patients, but changes in FIB‐4 and its association with HCC development after SVR have not been fully clarified. Methods: This study included 433 CHC patients who received interferon‐based antiviral therapy and achieved SVR between 2004 and 2014. FIB‐4 was estimated immediately before treatment, at 24 weeks after the end of treatment (SVR24), and at the last laboratory examination during follow‐up (last visit). Multivariate Cox proportional hazard analysis was used to estimate hazard ratios (HRs) of variables for HCC development. Cumulative incidences of HCC development were evaluated using KaplanMeier plot analysis and the log‐rank test. Results: During the median follow‐up time of 3.2 years (range: 1.0‐9.8 years), 11 of the 433 patients developed HCC The median FIB‐4 values at pretreatment, SVR24, and the last visit were 1.99, 1.71, and 1.68, respectively; the values at all the time points were significantly different from one another (P < 0.001). At each time point, patients who developed HCC had significantly higher FIB‐4 than those who did not develop HCC. The areas under the receiver operator characteristic curves indicated that pretreatment FIB‐4 predicted HCC development with high diagnostic accuracy (0.833) and was superior to the predictive value of FIB‐4 at SVR24 (0.747) and at the last visit (0.791). Multivariate Cox proportional hazard analysis demonstrated that only pretreatment FIB‐4 was significantly associated with HCC development (HR 1.58, P < 0.001). The cutoff value of pretreatment FIB‐4 was identified as 2.90. The 5‐year cumulative incidences of HCC development were 9.0% and 1.1% in patients with pretreatment FIB‐4 >2.90 and ≤2.90, respectively (P < 0.001). Conclusion: Although FIB‐4 decreased over time, patients with a high pretreatment FIB‐4 remain at high risk of HCC development after achieving SVR.

Disclosures:

The following people have nothing to disclose: Takuya Genda, Ayato Murata, Nozomi Amano, Sho Sato, Hironori Tsuzura, Shunsuke Sato, Yutaka Narita, Yoshio Kanemitsu, Yuji Shimada, Katsuyori Iijima, Akihito Nagahara, Sumio Watanabe

¹Division of Infectious Diseases, University of California San Diego, La Jolla, CA; ²Division of Global Public Health, University of California San Diego, La Jolla, CA; ³School of Medicine, University of California San Diego, La Jolla, CA

Background: International reports of a hepatitis C virus (HCV) epidemic among HIV‐positive men who have sex with men (HIV+ MSM) associated with recreational drug use with sex are causing concern. However, little is known about the HCV epidemic among MSM in San Diego. We assess the incidence of HCV among HIV+ MSM in San Diego. Methods: We performed a retrospective cohort analysis of HCV incidence among HIV+ MSM attending the largest HIV clinic in San Diego (UCSD Owen Clinic) from 2000‐2015. Incident HCV infection was assessed among HIV+ MSM with a baseline negative anti‐HCV test between 2000 and 2015. Incident infection was defined as any new positive anti‐HCV or HCV‐RNA test after the start of follow‐up Incidence was calculated using survival time methods Results: Among 2,091 baseline negative patients, 141 HCV seroconversions occurred over 12,926 person‐years at risk (incidence rate = 1.09/100 person‐years; 95%CI 0.92‐1.29). HCV incidence increased over time from 0.26/100py in 2000‐2003 to 1.42/100py in 2012‐2015 (Figure 1, tr test p=0.027). Individuals were tested a median of 3 ti (interquartile range[IQR] 2‐4) with a median testing intervc 1.2 years (IQR 0.6‐2.2). Incident cases were on average years in age, 11.8 years from HIV diagnosis to HCV diagno and 4.9 years from first HCV negative test to HCV diagno 17% (24/141) of MSM reported ever injecting drug use. H incidence was significantly higher (p<0.001) among M reporting IDU (2.6/100py, 95%CI 1.74‐3.88) comparer not reporting IDU (0.97/100py, 95%CI 0.81‐1.17), with significant differences in testing rates Conclusions: HCV i dence among HIV‐positive MSM in San Diego is increas with rates similar to London and other major European cit and double that observed in the US Multicenter AIDS Co Study This study also documented HCV infection among H MSM who do not inject drugs Further work determining epidemic trajectory and prevention required to control the demic is needed.

Disclosures:

David L Wyles ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, AbbVie; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb, AbbVie, Tacere

Natasha K Martin ‐ Grant/Research Support: Gilead; Speaking and Teaching: AbbVie, Merck, Gilead

The following people have nothing to disclose: Antoine Chaillon, Thomas C Martin, Edward R. Cachay, Davey M. Smith, Susan J. Little, Sanjay R. Mehta, Richard L Garfein

¹Gastroenterology, North‐ Shore University Health System, Chicago, IL; ²Oregon Health and Science University, Portland, OR

Purpose: Despite the 2012 CDC and 2013 USPSTF recommendations that patients born between 1945 and 1965 should receive one‐time HCV antibody testing, the majority of US baby boomers have not been screened to date, indicating gaps in the implementation of the guidelines. The primary aim of this study was to compare HCV screening rates between primary care and subspecialty clinic patients in an integrated healthcare system comprising over 250,000 baby boomers Methods: We identified all baby boomers presenting for at least one outpatient visit to internal or family medicine, gynecology, or other subspecialty clinics at NorthShore University HealthSystem in July 2015. Patients' electronic medical records (EMR) were searched for HCV antibody test results dating back to 2003 The frequency of HCV antibody testing was stratified by age, gender, prior history of HCV infection, and provider specialty. The influence of patient and physician characteristics on the frequency of testing was analyzed using multivariate logistic regression. Results: 12,344 patients met the HCV screening criteria during the one‐month sampling period. Of these, 1882 (15%) had undergone HCV antibody testing. Ninety (4.8%) screened patients were HCV antibody‐positive, and 84 of 90 patients (93%) underwent follow up HCV RNA testing. HCV‐ RNA was detectable in 61 of 84 antibody‐positive patients (73%). HCV testing was slightly less common in men (14%) than women (16%), and significantly more common in patients who were younger vs. older than age 65 (16% vs. 12%, respectively). The highest HCV screening rates were observed in gynecology clinic patients (17%), followed by internal medicine (16%), family medicine (13%), and other subspecialties including gastroenterology (10%). In the multivariate analysis all these characteristics, except gender, exerted an independent and statistically significant influence on HCV antibody testing. Among patients with a positive HCV antibody test result, the rates of HCV RNA testing were not affected by physician specialty or patient characteristics Conclusion: Overall, we observed a low adherence to HCV birth cohort screening guidelines among different outpatient settings in an integrated healthcare system, as EMR‐documented HCV antibody test results were found in only 15% of all eligible patients. Patients younger than age 65 were more likely to be tested than older patients, and there was significant variability between different specialty clinics, with screening rates varying from 10% to 17%. Our study identifies opportunities for increased HCV antibody screening efforts that could incorporate age‐ and clinic‐specific practice patterns.

Disclosures:

Jay L. Goldstein ‐ Advisory Committees or Review Panels: Aralez; Consulting: Aralez

Amnon Sonnenberg ‐ Grant/Research Support: Gilead

The following people have nothing to disclose: Amoah Yeboah‐Korang, Mohammad Beig, Claus Fimmel

¹Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA; ²Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA; ³Infectious Diseases, Boston Medical Center, Boston, MA; ⁴Lemuel Shattuck Hospital, Boston, MA; ⁵Infectious Diseases, Massachusetts General Hospital, Boston, MA

Background: Understanding the burden of HCV‐related hospitalizations in inmates is important to making rational policy about HCV treatment in prisons. We compared hospital lengths of stay and readmission by HCV infection status among inmates. Methods: Lemuel Shattuck Hospital (LSH) provides inpatient medical services to inmates in MA We used billing records to develop a database of inmate discharges from LSH 2004 to 2014. Data collected included: age, race, gender, date of admission & discharge, length of stay (LOS), all reported ICD‐9 codes, and disposition from hospital (died, back to prison, to another hospital). We identified HCV‐infected individuals by using HCV‐associated ICD‐9 codes (070.41,070.44, 070.51, 070.54, 070.70, 070.71). We compared HCV‐infected to un‐infected individuals The primary outcomes were LOS and odds of readmission to LSH. Logistic regression adjusted for confounding by age, sex, race, LOS of first admission, and co‐morbidities (Elixhauser index). Results: 4668 inmates contributed a total of 8397 discharges. 93% of inmates were male, 53% were white, median age at first hospitalization was 44 yrs (IQR 34, 52). HCV ICD‐9 codes were associated with of 20% of hospitalizations. Median LOS was 5 days (IQR 2, 9). Inmates with HCV were older (46 vs. 42, p<0.001) and had longer mean LOS (6 days vs. 5 days, p<0.001). In multivariable modeling, HCV remained associated with increased odds of readmission (1.3, CI (1.1‐1.6)). Conclusion: In MA, HCV‐infection is associated with 20% of inmate admissions, a 20% increase in LOS, and a 30% increase in the odds of readmission to the hospital Treatment may not avert all of the observed increase in hospitalization, but HCV is associated with many admissions and modest reductions in hospital utilization after SVR could help offset treatment costs.

Factors Associated with Readmission in Inmates (n = 4,668)

*When the Elixhauser Index variable was used in the multivariable model, HIV and Liver Disease were removed from the index.

Disclosures:

The following people have nothing to disclose: Alysse G. Wurcel, Deirdre J. Burke, Brian Engle, Kathryn Noonan, Tamsin A. Knox, Arthur Y. Kim, Benjamin P. Linas

¹liver unit, Centre Hospitalier, Perpignan, France; ²HEPATITIS MOBILE TEAM, PERPIGNAN, France

Introduction: Although highest european screening rate in France, 44% of patients didn't take care of hepatitis C because there were no diagnosed. Drug injection was main contamination route of hepatitis C virus (HCV) in France and western Europe since 1990. French guidelines were to treat all inmates and drug users, even fibrosis level. Access of HCV screening, care and treatment in drugs users, prisoners and homeless was low in France, less of 20%. They were considered as difficult to treat populations.. All these patients need support especially psycho‐educative interventions. Hepatitis Mobile Team (HMT) was created in July 2013 to increase screening care and treatment of hepatitis B and C patients We proposed 15 services: 1 Screening by Dried Blood Spot (DBS) HIV HBV HCV 2. Mobile Fibroscan* in different sites 3. Social screening and diagnosis (EPICES score) 4 Outreach center with specific health care workers 5 days/7 5. Free blood tests in primary care if no social insurance 6 Advanced on‐site specialist consultation 7. Access to obligatory pre‐treatment commissions. 8. Individual psycho‐educative sessions 9. Collective educative workshops 10. Staff training 11. Drug users prevention 12. Peer to peer program 13. Low cost specific patients mobile phones 14. Specific one day hospitalizations before and after antiviral treatment 15. Green thread: outside DBS and FIBRO‐ SCAN* in specific converted truck. Objective: increase screening care treatment access and cure of our target population Patients and methods Target population was drugs users, prisoners, homeless, precarious people, migrants and psychiatric patients. We proposed part or all of our services to our medical and social partners. They choose only services what they need. Results: from 2013 July to 2015 December, we did 2056 DBS for 1485 people (944 HCV DBS). Our HCV active file was 244 patients included 18% of new patients screened by DBS ; 83% realized all blood tests and FIBROSCAN; 59% need treatment according to French recommendations; 50% started treatment and 49% have been cured. Quality of program for patient were free access, closeness (outside hospital), speed (of the results) and availability (of nurse and social workers) Conclusions: Specific screening, follow up and support of these difficult to treat populations are essential for increase medical management and cure of HCV patients. HMT offered complement services and not substitution of existing services. It was new useful tool to screen, diagnosis and treat these patients by outside pathway of care.

Disclosures:

Andre Jean Remy ‐ Consulting: ROCHE, JANSSEN, GILEAD; Speaking and Teaching: BMS

The following people have nothing to disclose: Hakim Bouchkira, Patrice Lamarre, Stephane Montabone

Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Background and Aims: To evaluate the utility of liver stiffness measurement for the prediction of hepatocellular carcinoma (HCC) development and survival in chronic hepatitis C patients Method: We enrolled 1,130 patients in whom liver stiffness was measured using FibroScan® at the authors' hospital from December 2004 to December 2015. We excluded patients who had already achieved sustained virological response (SVR) at the initial liver stiffness measurement We assessed HCC development and overall survival based on liver stiffness using Kaplan‐Meier method. Results: The patients consists of 493 males and 637 females with median age of 64. Liver stiffness at the enrollment was ≤5 kPa in 235, 5.1‐10 kPa in 454, 10.1‐15 kPa in 190, 15.1‐20 kPa in 96, 20.1‐25 kPa in 57, and >25 kPa in 98, respectively. During the mean follow‐up period of 6.6 years, HCC developed in 191 patients. The cumulative incidence rates of HCC at 1, 2, 3, 5, 7, and 10 years were 1.9%, 4.9%, 7.4%, 12.1%, 17.3%, and 23.3%, respectively Cumulative HCC incidence rates at 5 years were 1.7% in those with ≤5 kPa, 3.3% in 5.1‐10 kPa, 16.4% in 10.1‐15 kPa, 25.4% in 15.1‐20 kPa, 38.4% in 20.1‐25 kPa, and 43.2% in >25 kPa, respectively (P <0.001). During the study period, 101 patients died. The cause of death was liver cancer in 30, liver failure in 17, gastrointestinal bleeding in 7, and others in 47 Overall survival rates at 1, 2, 3, 5, 7, and 10 years were 99.9%, 99.5%, 98.8%, 96.8%, 93.0%, and 86.7%, respectively Ten‐year survival rates were 99.3% in those with ≤5 kPa, 95.7% in 5.1‐10 kPa, 81.7% in 10.1‐15 kPa, 80.9% in 15.1‐20 kPa, 64.5% in 20.1‐25 kPa, and 48.3% in >25 kPa, respectively (P <0.001). Conclusions: Liver stiffness can predict long‐term outcomes over 5 years in chronic hepatitis C patients.

Disclosures:

Ryosuke Tateishi ‐ Grant/Research Support: Kyowa Hakko Kirin Co., LTD. ; Speaking and Teaching: Taisho Pharmaceutical Co, LTD., Bayer Yakuhi, Ltd., Otsuka Pharmaceutical Co., Ltd., AstraZeneca K. K., Eisai Co., Ltd., Gilead Sciences Co., Ltd., MSD K.K., Sumitomo Dinippon Pharma Co., Ltd., Covidien Japan Inc., Wako Pure Chemical Industries, Ltd

Yoshinari Asaoka ‐ Grant/Research Support: Kyowa Hakko Kirin Co Ltd ; Speaking and Teaching: Bayer Pharma

The following people have nothing to disclose: Ryo Nakagomi, Ryota Masuzaki, Taijiro Wake, Mizuki Nishibatake, Naoto Fujiwara, Masaya Sato, Tatsuya Minami, Kenichiro Enooku, Hayato Nakagawa, Yuji Kondo, Kazuhiko Koike

¹Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA; ²National Center for Disease Control, Tbilisi, Georgia; ³Division of Global Health Protection, Centers for Disease Control and Prevention, Atlanta, GA

Purpose: Georgia is the first country in the world to adopt a national HCV elimination goal, set for 2020. This abstract presents results from Georgia's first nationally representative hepatitis C virus (HCV) seroprevalence survey, which will be used to monitor progress toward HCV elimination Methods: A cross‐sectional, nationally representative seroprevalence survey of 7,000 individuals aged ≥18 years was conducted in Georgia from May‐August 2015 using a stratified, multi‐stage cluster design After giving informed consent, participants provided epidemiologic data including demographics, medical history, knowledge of HCV transmission and prevention methods, and HCV‐related risk factors. Blood specimens were collected from participants and tested for antibodies to HCV, and for HCV RNA. Data were weighted based on probability of selection and calibrated using census data on sex, age, and geography Descriptive statistics were computed. Results: Nationally, HCV seroprevalence was 7.7% (95% CI: 6.7‐8.9), and prevalence of chronic HCV infection was 5.4% (95% CI: 4.6‐6.4). Seroprevalence was 9.4% (95% CI: 6.9‐12.6) in the capital city (Tbilisi), 9.5% (95% CI: 8.0‐11.3) in urban areas overall, and 5.4% (95% CI: 4.4‐6.7) in rural areas Seroprevalence was highest among persons aged 40‐49 years (14.0%, 95% CI: 11.1‐17.6), males (12.1%, 95% CI: 10.2‐14.3), and persons reporting a history of injection drug use (IDU) (66.5%, 95% CI: 56.0‐75.6), incarceration (42.0%, 95% CI: 32.8‐51.7), or blood transfusion before and after Georgia began testing donor blood for HCV in 1997 (25.3%, 95% CI: 16.2‐37.3; 17.4%, 95% CI: 10.7‐27.1, respectively). A majority of respondents demonstrated knowledge that HCV can be transmitted through infected blood (56.1%, 95% CI: 53.9‐58.3) or by sharing needles or syringes (52.3%, 95% CI: 50.0‐54.6), and that HCV can be prevented by avoiding needle sharing (54.1%, 95% CI: 51.9‐56.3) and avoiding unsterile/used medical devices (50.0%, 95% CI: 47.4‐51.7). Less than half (38.9%) of seropositive respondents were aware of their infection, and 11.8% reported initiating treatment prior to the availability of all‐oral, direct‐acting antiviral drug regimens in Georgia. Conclusions: HCV seroprevalence in Georgia is high overall, exceeding 50% among persons reporting IDU, and is higher in urban than in rural settings. Among those who tested HCV antibody‐positive, awareness of infection was low, and most had not been treated. Knowledge of current nationwide HCV prevalence and associated risk factors will inform implementation of prevention, screening, and treatment strategies and will establish a baseline to track progress toward elimination over time.

Disclosures:

The following people have nothing to disclose: Liesl Hagan, Ana Kasradze, Stephanie Salyer, Amiran Gamkrelidze, Maia Alkhazashvili, Gvantsa Chanturia, Nazi Chitadze, Roena Sukhiashvili, Marina Shakhnazarova, Curtis Blanton, Steven Russell, Giorgi Kuchukhidze, Davit Baliashvili, Susan Hariri, Jan Drobeniuc, Paata Imnadze, Juliette Morgan, Francisco Averhoff

National Virus Reference Laboratory, University College Dublin, Dublin, Ireland

Introduction With the increasing number of licensed direct‐acting antivirals (DAA) for the treatment of chronic HCV infection, choosing the right treatment regimen for the right patient has become paramount. We believe baseline sequencing for the presence of resistance‐associated substitutions (RAS) is an important contributor to this decision‐making process In the present study in an Irish cohort, we performed a retrospective analysis on all HCV samples received for drug resistance testing at the Irish National Virus Reference Laboratory between September 2014 and May 2016. Particular attention was paid to patients who experienced virological failure in an attempt to identify predictors of failure. Methods Sanger sequence data covering the HCV NS3 protease coding region were obtained for 682 samples received during the study period. Sequence data for the NS5A and NS5B regions in some samples were also obtained. The rs12989860 single nucleotide polymorphism site was examined by allelic discrimination real‐time PCR. Results Analysis of the NS3 viral sequences demonstrated that 85.5% (583/682) were HCV subtype 1a, 14.2% (97/682) subtype 1b and 0.3% (2/682) subtype 1c infections. RAS proven to reduce susceptibility to NS3 inhibitor treatment were detected in 45.9% of cases (313/682). Although the vast majority of all RAS detected were found in subtype 1a viruses, 7.2% (7/97) subtype 1b samples also contained one or more RAS. The Q80K polymorphism was found in 313/583 (57.3%) of HCV subtype 1a, and almost exclusively in clade 1 (242/443; 54.6%) versus clade 2 viruses (2/140; 1.4%). Among the cohort of patients who experienced virological failure whilst on treatment, RAS could be detected in 11/17 (64.7%) patients for whom sequence could be generated. These included V36M/L (6/11; 54.5%), Q80K (5/11; 45.5%), R155K/T (3/11; 27.3%) and T54S (1/11; 9.1%). The majority of these patients were found to possess the deleterious “T” single nucleotide polymorphism (SNP) at the rs 12989860 site within the interleukin‐28B gene locus. Nine of eleven patients with detected RAS were found to also be either CT or TT at rs12989860, one patient was CC at this SNP Preliminary data from patients experiencing treatment failure on NS5A/B inhibitors also indicate the presence of RAS in 4 of 7 individuals. Discussion The high incidence of RAS within HCV NS3 protease sequences, the detection of RAS in NS5A sequences, and the apparent risk of treatment failure, albeit in a small number of patients, when the RAS are present, highlights the importance of sequencing these viruses prior to commencing treatment with protease inhibitors, and the need to identify additional predictors of failure.

Disclosures:

The following people have nothing to disclose: Jonathan Dean, Martha Neary, Suzie Coughlan, Cillian F. De Gascun

¹Medical Program, James J. Peters VA Medical Center, Bronx, NY; ²Dept. of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; ³Research Program, James J. Peters VA Medical Center, Bronx, NY

BACKGROUND: In acute hepatitis C virus (HCV) infection, 25‐40% of patients clear the infection spontaneously through immunological mechanisms Spontaneous clearance of chronic HCV infection without antiviral therapy has been described only in rare case reports. The frequency of such clearance is unknown as is the influence of HIV coinfection. METHODS: The HCV Clinical Case Registry of a single tertiary care facility was reviewed for all quantitative plasma HCV RNA levels measured from 1997 ‐ 2015 (19 years). Patients with at least one HCV RNA ≥3,000 lU/ml and no evidence of acute infection were included as chronically infected Cases of spontaneous clearance were defined as at least one HCV RNA <43 lU/ml or undetectable preceded by at least one HCV RNA ≥3,000 lU/mL with no antiviral therapy in the time interval between measures. RESULTS: Among 3,018 chronically HCV‐infected patients, 13 (0.43%; 95% confidence interval, 0.23% ‐ 0.74%) experienced spontaneous clearance. Five of the 13 patients were HIV/HCV‐coinfected, all of them with suppressed HIV RNA <400 copies/ml on antiretroviral therapy and a median CD4+ cell count of 444/mm3 (range, 198 ‐ 708). No patient was hepatitis B virus /HCV‐coinfected (HBsAg+), three had compensated cirrhosis, and one had a prior liver transplantation with HCV recurrence Among HIV/HCV‐coinfected patients, the frequency of spontaneous clearance was 1.07% (5 of 469; 95% C. I., 0.35% ‐ 2.47%), while in HCV‐monoin‐ fected patients, the rate was 0.31% (8 of 2,549; 95% C.I., 0.14% ‐ 0.62%). The risk ratio for spontaneous HCV clearance in HIV/HCV coinfection over HCV monoinfection was 3.40 (95% C. I., 1.12 ‐ 10.3, p=0.031). The rate of spontaneous clearance in chronic HCV genotype 1 (GT‐1) infection was 0.16% (95% C. I., 0.03% ‐ 0.46%), for GT‐2 it was 1.06% (95% C. I., 0.13% ‐ 3.79%), and for GT‐3 it was 2.74% (95% C. I., 0.33% ‐ 9.6%). The risk ratio for GT‐2 over GT‐1 was 6.8 (95% C. I., 3.0 ‐ 102.5, p=0.002), and for GT‐3 over GT‐1 it was 17.4 (95% C. I., 3.0 ‐ 102.5, p=0.002). CONCLUSION: Spontaneous clearance of chronic HCV infection without antiviral therapy is rare and occurs in about 0.4% of patients. Clearance is significantly more common in HIV/HCV‐coinfected than in HCV‐monoinfected patients and in GT‐2 and GT‐3 patients compared to GT‐1.

Disclosures:

The following people have nothing to disclose: Varun Jain, Diana Otero, Tatjana Gavrancic, Qing Liu, Sonja Marcus, Norbert Bräu

¹Brighton and Sussex Medical School, Brighton, United Kingdom; ²Gastroenterology and Hepatology, Brighton and Sussex University Hospital, Brighton, United Kingdom; ³Psychiatry, Surrey and Borders Partnership Trust, Brighton, United Kingdom; ⁴Susssex Partnership NHS Trust, Brighton, United Kingdom

Objective/aims: Majority (90%) of HCV positive individuals in England are people who inject drugs (PWID) with poor engagement with health services. Our on going study assesses feasibility of non‐invasive detection, staging and treatment of HCV. related chronic liver disease in the community. Methods: Four‐year prospective study (Dec 2013‐Nov 2017) conducted at a large substance misuse service in SE England. Individuals offered dry blood spot testing (DBST), mobile transient elastography (TE), HCV treatment (including DAA) and qualitative interviews with recent addition of patient reported outcomes (SF‐12v2, SFLDQOL) and health economics (EQ‐5D‐5L). Results: To date, 391 individuals recruited, 81% males with mean age of 40.0 yrs. (sd 9.8). There was high prevalence of injecting drug use (IDU) [274 (70%)], alcohol use [336 (86%)] and psychiatric illness [174 (45%)]. Uptake of dbst was 49% (n=190); prior testing being the main reason for declining. Prevalence of positive serological markers/PCR were: HBcAb 20% (n=71), HCV antibody 53% (n=200), HCV PCR 82% (163/200); genotypes 1=71 (44%) and 3= 79 (48%). On logistic regression, independent predictors of a positive HCV serology were if ever injected (OR 8.5, 95% CI 4.2‐17.4); positive HBcAb (OR 3.5 95% CI 1.9‐6.6) and a psychiatric diagnosis (OR 2.1, 95% CI 1.3‐3.5) Of those with a positive HCV PCR (n=163), 132 (81%) underwent TE [mean LSM kPa 9.9 (sd 10.3), 59 (36%) having LSM ≥ 7.5 kPa, 32 (20%) having cirrhosis (LSM ≥12 kPa). There was a significant association between a positive HCV serology and LSM >7.5 kPa: 72% of those with LSM<7.5 were positive compared to 98% with LSM ≥ 7.5 (p<0.001). None had had prior HCV treatment. Forty‐eight (29%) were not treatment candidates (chaotic lifestyle). Of the remaining (n=115), 50 commenced treatment. Characteristics of treated cohort were: age 45 yrs. (sd 10.2), 92% male, > 80% having substance/alcohol use, 86% undergoing TE, genotypes (1 = 41%, 3= (55%), treatment received: INF/ RBV 32%, INF+DAA=38% and daa 30% and treatment outcomes were: 35 (70%) SVR/EOTR, nine (18%) on‐going treatment, six (12%) NR (included four RR). Twenty‐ two have had pre‐treatment questionnaires done Conclusions: Prevalence of positive HCV serological markers remain high in PWID, which might explain the almost 40% prevalence of significant hepatic fibrosis. Compliance in this difficult to engage cohort was ∼ 90% with HCV treatment outcomes comparable to secondary care Our on going prospective study endorses the success of this novel, easy to replicate “one‐stop” community based HCV treatment model with onsite mobile TE.

Disclosures:

Margaret O'Sullivan ‐ Grant/Research Support: Gilead

Sumita Verma ‐ Grant/Research Support: Gilead, Brighton and Hove Commissioners, Dunhill Medical Trust, National Institute of Health Research, Janssen, Abbvie, BMS

The following people have nothing to disclose: Hugh Williams, Anna‐Marie Jones

¹School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; ²British Columbia Centre for Disease Control, Vancouver, BC, Canada; ³Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; ⁴Ontario HIV Treatment Network, Toronto, ON, Canada; ⁵Department of Statistics, University of British Columbia, Vancouver, BC, Canada

Background: T‐cell host immune response against hepatitis C virus (HCV) has been suggested to play important role in determining HCV outcomes which has not been examined in population‐based cohort studies. Concurrent hepatitis B (HBV) infection has been found a significant predictor of spontaneous clearance of HCV in high‐risk population This study examined the effect of these two along with other factors on the spontaneous clearance of HCV in a population‐based cohort in British Columbia, Canada Methods: The BC Hepatitis Testers Cohort (BC‐HTC) includes all individual tested for HCV between 1990 and 2013 linked with data on their medical visits, hospitalizations, and prescription drugs HCV positive individuals with at least one valid HCV PCR test on or after HCV diagnosis (n=46,783) were included in this study To examine factors associated with the spontaneous clearance of HCV, we fitted multivariable logistic regression on the full sample, and Cox proportional hazard model on the seroconverters i e HCV negative individuals who subsequently became HCV positive (n=6,238) Results: Spontaneous clearance was observed in 25.1% (n=11,737) of those tested for HCV. After adjusting for potential confounders, the odds of spontaneous clearance of HCV was lower in people with pre‐existing primary T‐cell immunodeficiency (adjusted odds ratio [aOR]: 0.55, 95% CI: 0.32‐0.94), and higher in females (aOR: 1.61, 95% CI: 1.54‐1.68), in those with pre‐existing HBV (aOR: 2.26, 95% CI: 1.89‐2.71), and in HCV infections with genotype‐3 (aOR: 2.23, 95% CI: 1.74‐2.86, compared to genotype‐1). Conclusion: Spontaneous clearance was lower for people with primary T‐cell immunodeficiency while it was higher among females, those with pre‐existing HBV, and HCV infections with genotype‐3.

Disclosures:

Mel Krajden ‐ Grant/Research Support: Roche, Merck, Siemens, Boerhinger Ingelheim, Hologic

The following people have nothing to disclose: Nazrul Islam, Mark Gilbert, Paul Gustafson, Mark Tyndall, Naveed Z. Janjua

¹Kirby Institute, UNSW Australia (University of New South Wales), Sydney, NSW, Australia; ²School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; ³Division of Global Public Health, University of California San Diego, San Diego, CA; ⁴Gilead Sciences, Inc, Foster City, CA; ⁵Centre for Social Research in Health, UNSW Australia (University of New South Wales), Sydney, NSW, Australia

Background: The Surveillance and Treatment of Prisoners with hepatitis C (SToP‐C) study is evaluating the impact of rapid scale‐up of interferon‐free HCV therapy on HCV transmission in prisons in New South Wales, Australia. This analysis characterises HCV epidemiology and risk behaviours among prisoners in two maximum‐security prisons in SToP‐C study. Methods: Data for this analysis includes prisoners enrolled from two maximum‐security prisons between October 2014 and March 2016. All prisoners over the age of 18 were eligible to participate At enrolment, participants received testing for HCV antibodies/RNA and completed a detailed survey, including injecting behaviours. Injecting behaviours by HCV infection/ exposure status were evaluated. Results: In March 2016, 393 prisoners were enrolled (Prison A: n=308; Prison B: n=85). The median age was 34 years (Q1‐Q3: 27, 44). The median duration of stay at the current prison at the time of enrolment was 2 years (Q1‐Q3: 0.9, 5). Overall, 54% (n=213) were HCV antibody negative (Ab‐), 18% (n=69) were HCV antibody positive/HCV RNA negative (Ab+/RNA‐; including 19 with self‐reported previous HCV treatment), and 28% (n=111) were HCV RNA positive (RNA+) Injecting illicit drugs during the current imprisonment was reported in 78% (83/111) of those RNA+, and 67% (46/69) of those Ab+/RNA‐, compared with 11% (24/213) of those Ab‐ (P<0.001). Injecting in the previous month was reported by 49% (54/111) of those RNA+, and 32% (22/69) of those Ab+/RNA‐, compared with 4% (8/213) of those Ab‐ (P<0.001). Among those injecting in the previous month, 86% (n=72) reported sharing injecting equipment. Conclusion: A high proportion of prisoners with HCV infection from maximum‐security prisons reported injecting risk behaviours Among prisoners at risk of HCV, those with previous HCV exposure and clearance were more likely to report high risk injecting than those with no previous exposure, suggesting the risk for re‐infection and the need for increased prevention activities. Surveillance of HCV incidence should focus on detecting both HCV re‐infection and primary infection.

Disclosures:

Jason Grebely ‐ Advisory Committees or Review Panels: Merck, Gilead; Grant/ Research Support: Merck, Gilead, Abbvie, BMS

Natasha K. Martin ‐ Grant/Research Support: Gilead; Speaking and Teaching: AbbVie, Merck, Gilead

John G. McHutchison ‐ Employment: gilead; Stock Shareholder: gilead

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead

Sciences

Andrew R. Lloyd ‐ Grant/Research Support: Merck, Gilead, Bristol‐Meyers Squibb Gregory Dore ‐ Board Membership: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Grant/Research Support: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Gilead, Merck, Abbvie, Bristol‐Myers Squibb

The following people have nothing to disclose: Behzad Hajarizadeh, Marianne Byrne, Philippa Marks, Tony Butler, Janaki Amin, Peter Vickerman, Carla Treloar

¹Universitätsklinik Frankfurt, Frankfurt, Germany; ²Institut für Biostatistik und mathematische Modellierung, Goethe‐Universität, Frankfurt, Germany

Background Regression of cirrhosis and portal hypertension (PT) is a major goal in treatment of patients with hepatitis C virus (HCV) associated cirrhosis. Improvement of Child‐Pugh‐ Turcotte (CPT)‐ and model of end stage liver disease (MELD)‐ scores were consistently observed in current trials investigating direct antiviral agents (DAA)‐based treatment in HCV associ‐ated cirrhosis. However, persistence of PT has been reported despite sustained virologic response (SVR) and improvement in CTP/MELD‐score. In the current study, we prospectively evaluated dynamics of liver and spleen stiffness in patients with HCV associated cirrhosis and SVR after DAA‐based antiviral treatment. Methods A total of 54 patients (69% male) with HCV associated cirrhosis and SVR after DAA‐based antiviral treatment were included Liver and spleen stiffness was assessed at baseline (BL), end of treatment (EOT), and 24 weeks after EOT (FU24) by transient elastography of the liver (L‐TE) as well as acoustic radiation force impulse (ARFI) of the liver (L‐ARFI) and spleen (S‐ARFI) Biochemical, virological and clinical data were obtained in parallel. Results There was a significant reduction of liver stiffness between BL [median (range), 32.5 (9.1‐75) kPa] and EOT [median (range), 21.3 (6.7‐73.5) kPa; p<0.0001) as well as between BL and FU24 [median (range), 21.2 (5.4‐70) kPa; p<0001)] by L‐TE. Liver stiffness assessed by L‐ARFI significantly decreased between BL [median (range), 2.7 (1.2‐4.1) m/s] and FU24 [median (range), 2.4 (1.2‐3.9) m/s; p=0.002), while spleen stiffness assessed by S‐ARFI did not decrease significantly between B, EOT and FU24. Improvement of liver stiffness was more pronounced between BL and EOT than between EOT and FU24 In addition, a significant improvement of MELD‐score between BL [median (range), 9 (6‐17)] and FU24 [median (range), 8 (6‐18)] was observed (p=0.01)]. Conclusion Liver, but not spleen elastography improved significantly in patients with HCV associated cirrhosis and SVR after DAA‐based antiviral therapy As this effect was mainly associated with the first 12‐24 weeks of treatment, it must be discussed to which amount improvement of liver stiffness was associated with decrease of hepatic necroinflammation or regression of fibrosis and portal hypertension Studies investigating only dynamics of CTP‐ and MELD‐score or liver stiffness may overestimate the degree of putative regression of cirrhosis.

Disclosures:

Tania M. Welzel ‐ Advisory Committees or Review Panels: Novartis, Janssen, Gilead, Abbvie, Boehringer‐Ingelheim+, BMS

Johannes Vermehren ‐ Advisory Committees or Review Panels: AbbVie, Abbott; Speaking and Teaching: AbbVie, Bristol‐Myers Squibb, Gilead, Medtronic

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

Martin W Welker ‐ Advisory Committees or Review Panels: Roche, Chiesi; Consulting: Amgen, Novartis; Speaking and Teaching: Bayer, BMS, Gilead The following people have nothing to disclose: Viola Knop, Daniel Hoppe, Eva Herrmann, Annika Vermehren, Mireen Friedrich‐Rust

¹College of Pharmacy, University of Florida, Gainesville, FL; ²College of Medicine, University of Florida, Gainesville, FL; ³Clinical and Translational Science Institute (CTSI), University of Florida, Gainesville, FL

Background: Hepatitis C Virus (HCV) infection is a major cause of chronic liver disease and associated with several extra‐hepatic manifestations. Several studies have demonstrated significant associations among HCV infection and insulin resistance, chronic kidney disease (CKD), and cardiovascular diseases (CVD). Conducted in Taiwan, it is unclear whether the results of these studies apply to US population given differences in prevailing genotype, level of comorbidities, and observed differences in the natural history of HCV. Objective: To assess the risk of CKD and CVD associated with chronic HCV infection in the U.S. Methods: A retrospective cohort analysis of the Truven Health MarketScan Database (2008 ‐ 2014) was conducted. Patients aged >=18 years with newly diagnosed HCV infection (ICD‐9: 070.44, 070.54, V02.62, 070.70, 070.71) were identified (HCV cohort). Outcomes included the incidence of CKD and CVD (coronary heart disease, cerebrovascular disease, peripheral arterial disease or congestive heart failure). Patients were excluded if they had experienced an outcome during 1 year prior to the first diagnosis of HCV. We matched the HCV cohort 1:3 with patients without HCV infection (non‐HCV cohort) using propensity score matching. Follow‐up continued until each study outcome, end of enrollment, or 31 December 2014, whichever comes first. We used Cox proportional hazards models to compare the risk of developing CKD and CVD between HCV and non‐HCV cohorts. Additional covariates adjusted in the model included alcohol/drug abuse disorders, HIV/AIDS, disease‐modifying medications, hepatitis B virus, cirrhosis, and so on. Results: The mean follow‐up time was 1.96 ‐ 2.24 years. The overall incidence rates of CKD were 114 and 43 per 10,000 person‐years in the HCV (72213 patients) and the non‐HCV cohorts (216639 patients), respectively The overall incidence rates of CVD were 55 and 29 per 10,000 person‐years in the HCV (59212 patients) and the non‐HCV cohorts (177637 patients), respectively. In multivariate adjusted models, HCV infection was associated with 2.2 fold higher incidence of CKD (hazard ratio (HR): 2.22; 95% confidence interval (CI): 2.01‐2.38) and an almost two fold higher incidence of CVD (HR:1.91; 95% CI:1.85‐1.97). Conclusions: The analysis of a large US administrative claim database suggests that patients with HCV infection are at greater risk of developing CKD and CVD than individuals without HCV infection Future studies are needed to investigate whether sustained virologic response to all‐oral direct‐acting antivirals alters the risk for development and/or progression of renal disease and cardiovascular outcomes.

Disclosures:

Haesuk Park ‐ Consulting: Gilead Science

David R. Nelson ‐ Grant/Research Support: Abbvie, BMS, Gilead, Merck, Janssen

The following people have nothing to disclose: Wei Wang, Chao Chen

¹Hospital Universitario San Cecilio e ibs. GRANADA, Complejo Hospitales Universitarios de Granada, Granada, Spain; ²ibs.GRANADA, Instituto de Investigacion Biosanitaria de Granada, Granada, Spain; ³CIBERehd, Ciber de Enfermedades Hepaticas y Digestivas, Granada, Spain

Background: Hepatitis C and B virus infections are highly prevalent worldwide and the main causes of liver disease both in children and in adults. The vertical transmission of HCV is a major route of HCV infection in children (>90%) In Spain, there has been a marked increase in the immigrant population in recent years and this may have changed the prevalence of HCV and HBV in pregnancy. The objective is to determine the prevalence and epidemiology of HCV and HBV in pregnant women in Spain Methods: A prospective cohort study was conducted at 10 National Spanish Hospitals 25,000 women (18‐42 years old), followed up in these Centers from January till October 2015, were enrolled. Prevalence of HCV (anti‐HCV+) and HBV (HBsAg+) was determined in this cohort and in a sub‐group of pregnant mothers Moreover, we studied the epidemiology of the HBV/HCV infection among pregnant mothers. Results: Overall HBV prevalence was 0.57% (0.55‐0.77; 25,289 women) and for HCV was 0.66% (0.55‐0.77; 21,379 women). The prevalence of these viral hepatitis was higher among women over 25 years of age However, the prevalence for HBV and HCV differ significantly between both groups (HBV and HCV prevalence in pregnant women: 0.42% and 0.21% respectively vs the prevalence of these viral hepatitis among women in fertile age: 0.99% and 0.80% respectively; p<0,05). Co‐infection data were: HBV/HCV: 0.036%, HBV/ HIV: 0.04% and HCV/HIV: 0.08% Caucasian and Chinese population were predominant in HBV prevalence whereas Caucasian, Latin and Gypsy population were in HCV. In relation to the country of origin, the VHB infected women were from: Spain (65%) and Eastern Europe (28%), and the HCV women were form: Spain (36%), Asia (25%, mainly China), Eastern Europe (16%), Africa (12%) and the South America (11%). The main risk factors for HBV infections were: vertical transmission (50%), presence of tattoo (18%) and personal antecedents of surgery (10%). However, for HCV infections were: the use of parenteral drugs, (56%), surgery (25%), tattoo (18%) and personal antecedents of transfusion (15%). Conclusions: An important percentage of women infected with these viruses are immigrant population The difference in HBV/HCV prevalence between pregnant and fertile age women may be due to: 1) the fertile age group had a high number of women with high risk to infection and 2) in relation to the HCV prevalence, HCV screening in Spain is not universal during the gestation and therefore it is performance mainly on high‐risk women The women over 25 years of age have an increased risk to viral hepatitis infection due to lack of prophylactic cares for HBV and to lack of HCV blood screening until 1990.

Disclosures:

The following people have nothing to disclose: Jose Antonio Munoz‐Gamez, Javier Salmeron, Angeles Ruiz‐Extremera

¹UCLA, Santa Monica, CA; ²VA Greater Los Angeles, Los Angeles, CA

Background: Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. Metabolic Syndrome (MS) is highly prevalent within the VA patient population and represents a heterogeneous group of patient with the potential for a genetic basis, especially in certain ethnic patient populations The increasing prevalence of this disorder can increase the likelihood for the progression to fibrosis, cirrhosis and hepatocellular carcinoma The risk of progression from chronic HCV infection to cirrhosis is highly variable, and many factors such as components of the MS are believed to accelerate disease progression and impact the likelihood of sustained virological response (SVR) MS has been thought to decrease the efficacy of antiviral therapies for chronic hepatitis C Newer hepatitis C treatment regimens are being used within the VA healthcare system and could affect HCV outcome in patients with MS Aim: To evaluate if the presence of meta‐bolic syndrome could overcome HCV treatment resistance in the era of direct‐acting antivirals (DAA). Methods: All patients undergoing HCV antiviral therapy with direct‐acting antivirals from 2014‐2016 were pooled for this analysis which was performed at the VA Greater Los Angeles HCS. We analyzed the SVR in a cohort of 1205 veterans with HCV with or without DM2, dyslipidemia, and hypertension as identified by ICD‐9 code or if the patients were currently on therapy. Results: SVR results in HCV treated patients with DM2, dyslipidemia and hypertension. Total number of DAA treated patients was 1205. Conclusion: These data suggest that the presence of metabolic syndrome does not adversely impact the antiviral treatment responses with the newer anti‐viral drugs. The importance of attaining SVR and reversal of progression of fibrosis remains to be evaluated.

Disclosures:

Alan J. Sheinbaum ‐ Advisory Committees or Review Panels: Gilead; Speaking and Teaching: Vertex

The following people have nothing to disclose: Jihane Benhammou, Christine Y. Yu, Jenna K. Kawamoto, Vivek Dixit, Neville Pimstone, Joseph R. Pisegna

¹Department of Medicine, University of Cincinnati, Cincinnati, OH; ²University of California‐ San Francisco, San Francisco, CA; ³lnstitute of Human Virology, University of Maryland, Baltimore, MD

Background: Hepatitis E virus (HEV) is an endemic, primarily zoonotic infection in the U.S. and Western Europe. Recent data from NHANES suggests that approximately 11% of the population has been exposed as evidenced by serologic testing. Some series have described higher rates of infection in those with HCV and/or HIV. We sought to evaluate the cross‐sectional prevalence of HEV in a large cohort of HCV and HCV/HIV coinfected patients. Methods: Serum samples were obtained from the HCVRES and HEPPRO Cohorts. These longitudinal cohorts were developed from HCV mono‐infected and HCV/ HIV coinfected persons seeking care at clinical facilities in the District of Columbia and surrounding environs Samples collected at or near the baseline enrollment period were evaluated. HEV IgG was evaluated using a sensitive ELISA assay (Wantai, Beijing, China), and the test was performed according to the manufacturer's instructions. Positives were confirmed by repeat duplicate testing as recommended by the manufacturer Parametric and non‐parametric testing was performed using Statistix 10.0. Results: 355 individuals ‐ including 184 HCV mono‐infected and 171 HCV/HIV co‐infected ‐ were tested for anti‐HEV IgG. The mean age was 56 years (range 21‐82 years), 76% were male, and 78% were black. The median CD4 was 711 cells/mm³ (range 62‐2328 cell/mm³) and was lower in HIV+ (mean= 595) vs HIV‐ enrollees (mean=983). Overall, anti‐HEV IgG was detected and confirmed in 18.6%. The proportions of confirmed cases were statistically similar regardless of HIV status (21.1% HCV vs 16.4% HCV/HIV, p = n.s.). Anti‐HEV prevalence was not affected by sex, race, or ethnicity in univariate analysis. HEV IgG was significantly more common in older (>60) vs. younger (≤60) participants (p = 0.0097). There was a modest inverse correlation between CD4 count and HEV IgG OD/Cutoff ratio (r = ‐0.32), and subjects with CD4<200 (AIDS definition) had HEV IgG OD/ Cutoff ratios significantly lower (mean 5.6) than those with higher CD4 counts (mean=11.9) among anti‐HEV IgG positive persons (p = 0.019). Conclusion: HEV exposure is higher in those with HCV and/or HIV than has been reported in general population surveys. Older HCV mono‐infected and HCV/HIV co‐infected persons are more likely to be exposed However, HCV/HIV co‐infected patients with low CD4 have less robust immune response as evidenced by lower antibody titers We speculate that this may lead to increased proportions of false negative results in this subgroup. Further evaluation of qualitative profiling of antibodies to HEV including determination of binding avidity are indicated.

Disclosures:

Kenneth E Sherman ‐ Advisory Committees or Review Panels: Janssen, Merck, Synteract; Grant/Research Support: MedImmune, Inovio, Merck, Gilead, Briston‐Myers Squibb

Norah Terrault ‐ Advisory Committees or Review Panels: Eisai, Biotest; Consulting: BMS, Merck, Achillion, CoCrystal; Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis, Merck

Jason Blackard ‐ Advisory Committees or Review Panels: NIH, South African Medical Research Council; Consulting: Merck, Inc; Grant/Research Support: Merck, Inc

The following people have nothing to disclose: Susan D Rouster, Mohamed Tarek M. Shata, Shyam Kottilil

¹Life sceinces, Seminar Hakibutzim College Israel, Ramat Aviv, Israel; ²Liver Unit, Shaare Zedek Medical Center, Jerusalem, Israel; ³Clinical Virology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel; ⁴Immunology Unit, Shaare Zedek Medical Center, Jerusalem, Israel; ⁵Bar‐Ilan University School of Medicine, Liver Institute Rabin Medical Center, Bar‐Ilan, Israel; ⁶Infectious disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel; ⁷The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL

Background: The incidence of acute hepatitis C (AHC) is declining worldwide. However, almost 30 years after the identification of the hepatitis C virus (HCV), new cases still occur. Since acute HCV infection is generally asymptomatic, it is seldom diagnosed. Thus, the specific mode of transmission, number of patients exposed, source of infection as well as the clinical and laboratory course of a given case can rarely be ascertained in real time. We describe an outbreak of AHC wherein all these parameters are known. Case reports: Three patients presented to our medical center with new onset jaundice between April 25th and May 9th 2016 (Table 1). AHC was diagnosed, and a review of the patient's histories identified a common potential source of exposure. All had CT scanning with IV contrast in one community imaging center on March 17th 2016. The last patient to undergo a CT at that center on March 16th was a known chronic hepatitis C patient. Health authorities were notified, and patients were summoned for testing. All 12 who had a CT with contrast on that day, were found to be positive for HCV RNA. Seven out of the 12 are treated in our medical center and described here (Table 1). Patients 1‐4 were followed‐up closely and their viral load declined significantly without antiviral treatment Patient number 5 is undergoing workup for a lung mass and deferred treatment. Patients 6 and 7 are treated with DAA because of patient's preference, and non declining viral load, respectively. Conclusions: Iatrogenic acute hepatitis C still occurs due to a combination of technical [e.g., multi‐dose vials] and human factors. Given that AHC rarely leads to fulminant hepatic failure, knowing the exact date of infection and close monitoring of the viral load presented a unique opportunity to follow the patients and their viral load closely. In anticipation of spontaneous viral clearance, treatment should be offered only when viral load does not decline. Thus, every effort should be made to ascertain the date of infection and to contact all patients potentially exposed. We aim to quantitate the clinical observation that more severe AHC leads to a greater chance of spontaneous recovery.

Table 1. Clinical data of the seven AHC patients treated at SZMC

Disclosures:

The following people have nothing to disclose: Orlev Levy‐Nissenbaum, Eyal Shteyer, Inna Gafanovich, Dana G. Wolf, Heftziba Ivgi, Ilana Dery, Rima Barsuk, Daniela Armoni, Michal C. Eliav, Yizhak Skorochod, Gabriel S. Breuer, Ran Tur‐ Kaspa, Yonit Wiener‐Well, Scott Cotler, Harel Dahari, Yoav Lurie

¹Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY; ²Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ³Department of Internal Medicine, Mayo Clinic, Rochester, MN

Background/Objectives: Hepatitis C virus (HCV) infection is a major cause of cirrhosis worldwide. Several studies have linked HCV infection to a higher risk of developing intrahepatic cholestasis of pregnancy (ICP), but the results were inconsistent. This meta‐analysis was conducted with the aim to assess the associations between ICP and HCV infection before and after the diagnosis of ICP. Methods: This study consists of two meta‐analyses. A literature search was performed using MEDLINE and EMBASE from inception to January 2016. The first study included observational studies that reported relative risks, odds ratios, or hazard ratios of the associations between HCV infection and risk of ICP. The second analysis included studies comparing the risk of later HCV infection in ICP patients with those without ICP. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random‐effect, generic inverse variance method. Results: Three studies were included in the first analysis. The pooled RR of ICP in HCV‐infected pregnant women compared to non‐HCV pregnant women was 20.40 (95% CI, 9.39‐44.33, I² =55%). Two studies were included in the second analysis. The pooled RR of later HCV infection among ICP patients compared to non‐ICP patients was 4.08 (95% CI, 3.13‐5.31, I²=0%). Conclusions: Our study demonstrated an increased risk of ICP among HCV‐infected pregnant women and also increased risk of later HCV infection among ICP patients. Physicians should be aware of this association, and we strongly suggest testing for hepatitis C in women with signs of ICP.

Forest plot of the included studies of the associations between hepatitis C infection and risk of intrahepatic cholestasis of pregnancy (Top).

Forest plot of the included studies of the associations between intrahepatic cholestasis of pregnancy and risk of later hepatitis C infection (Below).

Disclosures:

The following people have nothing to disclose: Karn Wijarnpreecha, Charat Thongprayoon, Sikarin Upala, Anawin Sanguankeo, Patompong Ungprasert, Wisit Cheungpasitporn

¹Gastro Study Center Berlin, Berlin, Germany; ²ifi‐institute for interdisciplinary medicine, Hamburg, Germany; ³University Hospital of Würzburg, Würzburg, Germany; ⁴Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; ⁵Universitätsklinikum Schleswig‐Holstein (UKSH), Campus Kiel, Kiel, Germany; ⁶Leberstudienzentrum Kiel GbR, Kiel, Germany; ⁷Center of Gastroenterology, Herne, Germany; ⁸e.factum GmbH, Butzbach, Germany; ⁹MVZ Dr. Eisenbach Dr.Simon Dr.Schwarz GbR, Leverkusen, Germany; ¹⁰Department of Hepatology, University Hospital Leipzig, Leipzig, Germany; ¹¹Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; ¹²Department of Internal Medicine I, J.W.Goethe University Hospital, Frankfurt, Germany; ¹³Leberstiftungs‐GmbH Deutschland, Hannover, Germany

Introduction: Treatment decision making with direct acting antivirals (DAA) in patients with chronic hepatitis C (CHC) is mainly based on baseline HCV RNA concentration, the HCV genotype and the presence or absence of liver cirrhosis. Since estimation of liver fibrosis by histology results has low acceptance, transient elastography (TE) and serum scores are often used in addition to clinical findings. Here, we assessed the diagnostic accuracy of a panel of non‐commercial serum scores in comparison to TE. Methods: The DHC‐R (Deutsches Hepatitis C‐Register, German Hepatitis C‐Registry) is a national multicenter real‐world cohort including approx. 9,300 patients. Patients are treated at the discretion of the physician. Data are collected by a web‐based system. Data quality is analyzed by plausibility checks and on site monitoring. This data analysis is based on 6,034 patients who were observed for at least 40 weeks after initiation of antiviral treatment. Valid data on TE were available for 1,742 patients. In those patients, the non‐commercial serum sores APRI score and FORNS index were calculated and the diagnostic accuracy was compared to FS results. Results: As estimated by TE, 625 (35.9%) patients had no significant fibrosis (SF) (<7,1 kPa), 530 (30.4%) patients had SF (>7.1kPa) and 587 (33.7%) patients had liver cirrhosis (>12.5kPa). Patients with liver cirrhosis were more frequently men, were older, had a higher BMI, had a longer estimated duration of disease and were more likely treatment‐experienced. SVR rates following different DAA regimens with or without ribavirin for 8 ‐ 24 weeks were 98.2%, 96.8%, and 92.4% for patients with no SF, SF, and cirrhosis, respectively. For discrimination of SF, AUROCS were: 0.79l (APRI score), 0.840 (FORNS index) For discrimination of cirrhosis, AUROC was 0.879 (APRI score). Conclusions: In our national multicenter real world cohort, significant fibrosis and cirrhosis were predicted with accuracy between 79‐84% and 87% with non‐commercial serum scores as compared to FS results Our data support the use of serum scores when TE is not available for accurate cirrhosis estimation SVR rates in patients with cirrhosis were numerically lower with current DAA regimens.

Disclosures:

Peter Buggisch ‐ Advisory Committees or Review Panels: Janssen, AbbVie, BMS; Speaking and Teaching: Falk, MSD, Gilead, Merz Pharma

Hartwig H. Klinker ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, Hexal, Janssen, MSD; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, MSD, Arrowhead, Novartis; Speaking and Teaching: AbbVIe, BMS, Gilead, Janssen, MSD

Stefan Mauss ‐ Advisory Committees or Review Panels: BMS, AbbVie, ViiV, Gilead; Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD

Rainer Günther ‐ Speaking and Teaching: Roche Pharma AG, Gilead, AbbVie

Holger Hinrichsen ‐ Advisory Committees or Review Panels: BMS, Janssen, Gilead, Abbvie; Speaking and Teaching: MSD

Dietrich Hueppe ‐ Advisory Committees or Review Panels: Roche, MSD, Novatis, Gilead, BMS, Janssen, AbbVie

Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Karl‐Georg Simon ‐ Advisory Committees or Review Panels: AbbVie, BMS, JANSSEN, MSD; Speaking and Teaching: AbbVie, BMS, FALK, GILEAD, JANSSEN, NORGINE, MERZ, MSD

Thomas Berg ‐ Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis, Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Merck/MSD, Novartis, Merck, Bayer, Abbvie

Michael P Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie Deutschland GmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

The following people have nothing to disclose: Wolf Peter Hofmann, Mireen Friedrich‐Rust

¹School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada; ²Clinical Prevention Services, BCCDC, Vancouver, BC, Canada; ³Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; ⁴Ontario HIV Treatment Network, Toronto, ON, Canada; ⁵Epidemiology and Surveillance, BC Centre for Disease Control, Vancouver, BC, Canada; ⁶BC Centre for Disease Control, Vancouver, BC, Canada; ⁷TB Services, BC Centre for Disease Control, Vancouver, BC, Canada; ⁸Fraser Health, Surrey, BC, Canada; ⁹University of British Columbia, Vancouver, BC, Canada

We examined the coevolution of HIV and HCV infections, mental illnesses, substance use and disparities over time in BC during 1990‐2013 using the BC Hepatitis Testers Cohort (BC‐HTC). The BC‐HTC includes ∼1.5 million individuals tested for HCV or HIV, or reported as a case of HCV, HIV, HBV, or tuberculosis linked to administrative healthcare databases. We classified individuals into HIV‐/HCV‐, HIV+/HCV‐, HIV‐/HCV+ seroconverters, HIV‐/HCV+ prevalent, and HIV+/HCV+. Of 1.37 million eligible individuals, 4.1% were prevalent HCV infection, 0.5% HIV‐monoinfected, 0.3% HIV/HCV co‐infected and 0.5% were HCV seroconverters. Overall, HIV monoinfected individuals lived in urban areas (92%), had low injection drug use (IDU, 4%), problem alcohol use (4%) and were materially more privileged than other groups. HIV/HCV co‐infected and HCV seroconverters were materially most deprived (14%, 12%), had higher IDU (34%, 53%), problem alcohol use (15%, 17%) and major mental illnesses (12%, 21%). HIV, HCV and HIV/HCV co‐infection began to increase in rural areas after 2004. Material deprivation, IDU and opioid substitution therapy increased overtime among seroconverters. Multivariable multinomial regression models mirrored descriptive trends Overtime, odds of IDU declined among HCV prevalent and HIV monoinfected individuals but not in seroconverters. Decline in odds of problem alcohol use were observed in seroconverters and coinfected individuals overtime (Figure 1). Results could inform optimal alignment of prevention, care and support services for HIV and HCV infected population within the context of changing epidemiology, disparities and risk profiles of these groups.

Adjusted log odds ratios of risk factors for HIV/HCV groups by time periods

Disclosures:

Mel Krajden ‐ Grant/Research Support: Roche, Merck, Siemens, Boerhinger Ingelheim, Hologic

The following people have nothing to disclose: Zahid Butt, Nabin Shrestha, Margot E. Kuo, Dionne Gesink, Mark Gilbert, Jason Wong, Amanda Yu, Maria Alvarez, Hasina Samji, Jane A. Buxton, James C. Johnston, Victoria Cook, David Roth, Theodora B. Consolacion, Michelle Murti, Gina Ogilvie, Robert Balshaw, Mark Tyndall, Naveed Z. Janjua

¹National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD; ²Social & Scientific Systems, Inc., Silver Spring, MD

Chronic liver disease and cirrhosis was the 12^th leading cause of death in the U.S. in 2014. Viral hepatitis leads to significant morbidity and mortality. We used national databases to update estimates of the viral hepatitis burden in the U.S. Methods: The National Ambulatory and Hospital Ambulatory Medical Care Surveys, Nationwide Inpatient Sample, and Vital Statistics of the U.S. databases were used to estimate medical care and mortality with a primary or other diagnosis of viral hepatitis B or C. Rates were age‐adjusted and shown per 100,000 population for the most recent year available Results: Hepatitis C contributed to 1.8 million ambulatory visits, 606,000 hospital discharges, and 20,000 deaths Ambulatory visit and hospital discharge rates were higher in middle compared with older age, and among men and African Americans compared with women and whites, respectively Both rates increased significantly from 1993 to 2013; however, greater availability of treatment options might have contributed to this rise Mortality rates were higher in middle compared with older age, and among men compared with women (7.2 vs. 2.8) and African Americans compared with whites (7.8 vs. 4.7). The mortality rate increased in the overall population by 6‐fold from 1993 to 2014 (0.8 to 4.9) and in demographic subgroups (Figure). Hepatitis B contributed to 462,000 ambulatory visits, 72,000 hospital discharges, and 2,000 deaths Ambulatory visit and hospital discharge rates were higher in middle compared with older age, and along with mortality rates were higher among men, African Americans, and non‐Hispanics compared with women, whites, and Hispanics, respectively Both medical care rates doubled from 1993 to 2013; in contrast, mortality rates declined by one third. Conclusions: The viral hepatitis burden in the U.S. today primarily reflects that of hepatitis C and is greater among men and African Americans.

Disclosures:

The following people have nothing to disclose: Aynur Unalp‐Arida, Constance E Ruhl

¹Public Health Sciences, Loyola University Chicago, Maywood, IL; ²Department of Medicine, Stritch School of Medicine, Maywood, IL; ³Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; ⁴KNUST, Kumasi, Ghana

Purpose: This population‐based study sought to determine age‐ and region‐specific Hepatitis C Virus (HCV) estimates in Ghana, where lack of available data and assessment has led to uncertainty regarding the burden of disease Methods: The study sample consisted of 2985 individuals currently located in the Ashanti region of Ghana Study participants completed a survey and an Oraquick rapid screen assay for HCV status. Those with positive screening tests underwent confirmatory testing with a CIA HCV antibody assay to confirm seropositivity. Age, gender, and region of origin were identified for each participant. Bayesian logistic regression was used to obtain odds ratios for assessing risk of HCV and age‐ and region‐specific prevalence estimates. Median posterior estimates are reported with 95% highest posterior density (HPD) credible intervals. Results: The average age of participants was 31.3 (range: 3‐103) years, and 70% of subjects were women. Children under the age of 15 comprised 22% of the sample, and 59% of individuals originated from the Ashanti region, 18% from northern regions, and 23% from other regions of Ghana Compared to Ashanti‐born subjects, the age‐adjusted odds of HCV infection were 15.6 (HPD: 2.7‐38.0), 22.9 (HPD: 9.2‐44.8), and 18.6 (HPD: 5.3‐39.4) higher for those originating from the Northern, Upper West, and Upper East regions, respectively These odds corresponded to HCV prevalence estimates of 4.3% (95% HPD: 1.1%‐9.0%), 6.1% (HPD: 3.7%‐9.1%), and 5.0% (HPD: 2.0%‐8.8%) in the Northern, Upper West, and Upper East regions, compared to 0.3% in Ashanti After adjusting for region of origin, the lowest prevalence was in the 0‐14 (0.9%; HPD: 0.4%‐1.5%) and 15‐24 (0.4%; HPD: 0.1%‐1.0%) age groups, respectively. Beginning at age 25, region‐adjusted prevalence increased to 1.9% (HPD: 0.8%‐ 3.3%) and peaked at 3.3% (HPD: 1.0%‐6.5%) among 55‐64 year olds before declining to 1.9% (HPD: 0.3%‐5.1%) in individuals 65 and older. A sub‐analysis involving only subjects originally from the northern regions (Northern, Upper West, Upper East) suggested age‐specific prevalence may be even higher in the North, with prevalence estimates of 6.9% (HPD: 3.0%‐11.6%) among 25‐34 year olds and increasing to 12.6% (HPD: 4.5%‐23.2%) among individuals 55‐64 years old. Conclusion: Significant age and regional differences in HCV prevalence exist in Ghana, with higher prevalence among individuals originating from the northern regions and among individuals ages 25‐64, with very few cases observed among participants less than 25 years of age Such findings suggest either an age cohort effect or transmission exposures that are low in childhood and increase with age.

Disclosures:

The following people have nothing to disclose: Stephanie Kliethermes, Jason Gantenberg, Nallely Mora, Richard O. Phillips, Ohene Opare‐Sem, Dorcas Owusu, Jennifer E. Layden

National Hospital Organization, Nagasaki Medical Center, Omura, Japan

Background As optimal management of chronic liver disease depends on the degree of liver fibrosis, accurate, but non‐invasive evaluation of liver fibrosis is of importance Though liver stiffness measurement (LSM) using Fibroscan and serum Wisteria floribunda agglutinin‐positive Mac2 binding protein (M2BPGi) were novel, noninvasive, and reliable technique to assess the degree of liver fibrosis, trans‐etiological comparison between two parameters has not yet been available in the literature. The aims of this study were to assess the correlation between LSM and serum M2BPGi levels among Japanese patients with hepatitis B, C and NAFLD. Methods A total of 1,347 patients who underwent LSM between 2012 and 2015 at our hospital were reviewed. 224 patients whose LSM value were invalid or failure were excluded Among the remaining 1123 patients, 782 patients (282 patients infected with HBV, 450 patients infected with HCV, and 50 patients with NAFLD) were enrolled in this study. Serum WFA(+)M2BP, aspartate transaminase to platelet ratio index (APRI), and fibrosis index to platelet ratio index (FIB4) were simultaneously measured and calculated on the occasion of LCM. Results The baseline characteristics of eligible patients were 393(50.3%) male with a median age of 64.5 years The median value of LSM, M2BPGi, APRI, and FIB4 were 5.6 kPa (2.3‐ 75.0), 0.9 COI (0.1‐21.0), 0.5 (0.1‐ 9.1), and 2.1(0.2‐23.9), respectively. Positive correlations between LSM and M2BPGi level (R2=0.46, p<0.001), APRI (R2=0.43, p<0.001), and FIB4 (R2=0.32, p<0.001) were observed; multiple linear regression analysis revealed M2BPGi level as the most significantly associated factor (effect size=0.46, p<0.001). Correlation coefficient between LSM and each fibrosis marker were as follows, in ascending order; HBV (R2=0.16, p<0.01), NAFLD (R2=0.46, p<0.01), and HCV (R2=0.53, p<0.001). The diagnostic performance of M2BPGi, APRI and FIB4 were evaluated using receiving operating characteristic curve analysis; AUC of M2BPGi, APRI and FIB4 were 0.83, 0.83, 0.78 in LSM level ≥7, 0.89, 0.88, 0.85 in LSM level ≥10, 0.89, 0.88, 0.85 LSM level ≥13, respectively. The optimal cutoff values of M2BPGi which best predicted LSM level ≥7 and ≥13 were 1.4 and 2.7, respectively. The optimal cutoff values of M2BPGi which best predicted LSM level ≥7 in distinct etiologies (HBV, NAFLD, and HCV) were 0.9, 1.0 and 2.0, respectively. Conclusions LSM values measured by Fibroscan were closely correlated with serum M2BPGi levels, compared to either APRI or FIB4, especially in hepatitis C patients Consideration of the etiology of liver diseases is required with regard to the prediction of LSM by M2BPGi cutoff values.

Disclosures:

Seigo Abiru ‐ Grant/Research Support: CHUGAI PHARMACEUTICAL CO.,LTD.

The following people have nothing to disclose: Shinjiro Uchida, Kazumi Yamasaki, Kohei Hayashi, Yuki Kugiyama, Shigemune Bekki, Satoru Hashimoto, Akira Saeki, Shinya Nagaoka, Atsumasa Komori, Hiroshi Yatsuhashi

¹University of Guadalajara, Jalisco, Mexico; ²Molecular Biology in Medicine, Civil Hospital of Guadalajara, Guadalajara, Mexico

Background. Host, viral and environmental interactions play a major role in the clinical outcomes of HCV infection. Spontaneous clearance (SC) may be associated with immunological mechanisms, as well as genetic and metabolic factors related with serum lipids. Therefore, Apolipoprotein E (ApoE) isoforms interacting with low‐density lipoprotein cholesterol (LDL‐c) could alter the course of the disease Aim. To analyze the anthropometric, metabolic and lipid alterations of SC patients and the association of ApoE alleles and LDL‐c with SC. Methods. Totally, 299 treatment‐naïve, anti‐HCV positive patients were included. Patients were classified in chronic hepatitis (CH) (n=206) who had at least two detectable viral loads (VL), and SC (n=93) after two undetectable VL in the last 12 months. A clinical record was elaborated for all participants. Body mass index (BMI) was evaluated by electric bioimpedance (InBody 3.0) Biochemical tests were accessed by dry chemistry assay VL was determined by COBAS® TaqMan 48 HCV test. Liver damage was evaluated by transitional elastography, and ApoE genotypes were identified by TaqMan Real‐Time PCR Results. No statistical differences were detected in age, gender, and risk factors for HCV infection between groups However, BMI was higher in SC than CH, predominating more CH patients with normal weight than sc (36.6% vs. 19.5% p=0.007). Total cholesterol (CHol) and hypercholesterolemia (>200 mg/dl) was higher in sc than CH patients (184.1 ± 43.3 mg/dL vs. 148.1 ± 43.3 mg/dL, p<0.001 and 32.6% vs. 9.8% p<0.001, respectively). No significant differences were detected in insulin resistance and type 2 diabetes between SC and CH groups (55.4% vs 43.5% p=0.072; 14.1% vs. 7.8% p=0.183, respectively). Liver damage was detected (37.5%, 18/48) in SC patients despite the low levels of ALT and AST (below 50 IU/mL each). The ApoE e4 allele frequency was significantly higher in the SC patients compared to CH group (p=0.042) Also, in the e4 allele subgroup, total CHol and LDL‐c values were higher in patients with SC compared to CH patients (193 ± 42 mg/dL and 125.2 ± 35.9 mg/dL vs. 160.5 ± 45 mg/dL and 101.9 ± 42.4 mg/dL, respectively). LDL‐c, e4 allele and BMI were associated with SC (OR=0.20, 95% CI 0.10‐0.41, p<0.001; OR=0.55, 95% Cl 0.313‐0.987, p=0.042; OR=0.37, 95% CI 0.18‐0.76, p=0.007), whereas ALT was associated as a risk factor for CH (OR=5.67, 95% Cl 2.69‐11.97, p>0.001). Conclusions. LDL‐c, e4 allele, and BMI were independent factors for SC. Cholesterol and LDL‐c levels modulated by genetics or dietary factors may influence the natural history and long‐term outcome of HCV infection.

Disclosures:

The following people have nothing to disclose: Karina Gonzalez‐Aldaco, Sonia Roman, Nora A Fierro, Erika Martinez‐Lopez, Rafael Torres‐Valadez, Maria Elena Trujillo‐Trujillo, Arturo Panduro

¹Department of Medical Education, Icahn School of Medicine at Mount Sinai, New York, NY; ²Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, NY; ³Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

Background: New treatments for HCV allow the majority of patients to achieve a sustained virological response (SVR); however, many patients with advanced liver disease continue to have impaired liver function Non‐invasive tests are needed to predict their clinical course Many centers routinely perform CT/MRI imaging on patients with advanced liver disease, providing data that can be used to calculate liver and spleen volumes. Aim: To assess pre‐treatment liver volume as a predictor of post‐SVR liver function Methods: The study group was comprised of cirrhotic patients who achieved an SVR and who had impaired liver function, defined as serum albumin ≤ 3.4 g/dL, prior to the start of treatment. Pre‐treatment liver and spleen volumes were calculated from CT/MRI images obtained within one year of the start of HCV treatment and were adjusted for ideal body weight using Vitrea software Demographic, anthropometric and other medical record data were collected pre‐ and post‐SVR. Logistic regression was used to identify factors associated with recovery of liver function, defined as a post‐SVR albumin level > 3.4 g/dL. Results: The median pre‐treatment age of the 49 patients was 61 years (IQR: 56 ‐ 65) (n=49); albumin, 3.0 g/dL (2.8 ‐ 3.2); MELD score, 14 (IQR: 11 ‐ 15); liver volume, 1264 mL (1078 ‐ 1555); and spleen volume, 537 mL (366 ‐ 839). Liver function returned to normal in 59% (29/49) of the patients Recovery (albumin normalization) was significantly related to higher liver volume pre‐treatment [odds ratio (OR): 1.2 per mL/kg, p=0.008], lower spleen volume (OR: 0.89 for every mL/kg, p=0.032), and lower MELD score (OR=0.56 for every 1‐unit increase in MELD score, p=0.002) In a subgroup‐analysis of 28 patients with a pre‐treatment albumin ≤ 3.0 g/dL, liver function returned to normal in 14 (50%). There was a strong trend toward an association between recovery and higher liver volume (OR: 1.2 per mL/kg, p=0.07) and lower spleen volume (OR: 0.84 per mL/kg, p=0.06). Recovery was significantly related to lower MELD score (OR: 0.62 for every 1‐unit increase in MELD score, p=0.04). Quality control tests performed on liver explants (n=16) and spleen explants (n=8) of known volume revealed that liver and spleen volume computed from CT/MRI accurately estimated liver weight (median error = 6.1%, IQR: 3.5% ‐ 12%) and spleen weight (median error = 15%, IQR: 4.4% ‐ 33%), validating the approach Conclusions: Liver and spleen volumes may be sensitive, non‐invasive prognostic indicators of liver functional status in the growing number of patients with advanced liver disease who achieve an SVR. Acknowledgements: DA 031095, DK 090317.

Disclosures:

Kian Bichoupan ‐ Consulting: Janssen, Gilead

Andrea D. Branch ‐ Grant/Research Support: Gilead, Galmed

The following people have nothing to disclose: Roberta K. Sefcik, Jasnit Makkar, Joshua Hartman, James F. Crismale, Neal M. Patel, Sweta Chekuri, Sara C. Lewis, Bachir Taouli, Thomas Schiano

¹Hepatology Unit, Cochin Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France; ²INSERM U‐818 and USM20, Institut Pasteur, Paris, France; ³Nephrology Unit, HEGP, APHP, Paris, France; ⁴INSERM UMR970‐PARCC, Paris Descartes University, Paris, France; ⁵UPMC Univ Paris 06, INSERM, Institut Pierre Louis d'épidémiologie et de Santé Publique (IPLESP UMRS 1136), Sorbonne Universités, Paris, France; ⁶Internal Medecine‐Digestive Department, CHU Purpan, Purpan, France; ⁷UMR152, IRD, Toulouse 3 University, Purpan, France; ⁸Nephrology Department, Tenon Hospital, Paris, France; ⁹Department of Hepatology and Gastroenterology, CHRU Claude Huriez, Lille, France; ¹⁰U1018,Centre for Epidemiology and Population Health ‐ Renal and Cardiovascular, INSERM, Villejuif, France; ¹¹Unité de Santé Publique, Assistance Publique‐Hôpitaux de Paris, Hôpital Saint Antoine, Paris, France; ¹²Inserm U897, Centre of Epidemiology and Biostatistics, ISPED Bordeaux School of Public Health, CHU de Bordeaux, University Bordeaux Segalen, Bordeaux, France

Background: Patients with chronic HCV infection have an increased risk of chronic kidney disease (CKD) and kidney failure. Hepatitis C virus (HCV) is also more common in CKD patients than in the general population The purpose of this study was to estimate the prevalence of CKD (stage ≥3) in HCV infected patients and to look for correlation with the liver disease severity. Patients and methods : We analyzed the estimated glomerular filtration rate (eGFR) using CKDEPI formula in patients with a positive virus C serology in a multicenter observational prospective national cohort Hepather CO‐22 (n = 20802). Exclusion criteria was kidney transplant recipient. Results : The analysis included 8571 patients (pts) from HCV 12 456 pts. The characteristics were: 56% men;57 ± 20 years;30% hypertensive;HCV since 17 ± 13 years;detect‐ able HCV RNA in 96%;genotype 1, 2, 3, 4 and 5/6/7 in 66%, 6%, 13%, 13% and 2%, respectively;40% of cirrhotic patients (96% Child A and MELD average 8 ± 3);and 59% previously treated with anti‐viral combination C (including an association with interferon and ribavirin 67%) The prevalence of an eGFR≤60 ml/min at inclusion was 6.3%. In univariate analysis, risk factors were sex, age, BMI, duration of infection, HCV treatment, diabetes, hypertension, high cholesterol, level of education, a history of heart disease, liver transplantation, the genotype (without influence of the stage of fibrosis, cirrhosis and Child score) In multivariate analysis, predictors of IRC were [Table 1] Conclusion : In ANRS C0‐22 HEPATHER cohort, the CKD prevalence was 7.3% and was associated with age, hypertension, diabetes, hypercholesterolemia, and history of cardiac disease but not the severity of the liver disease (cirrhosis, Child and MELD scores) Longitudinal analysis will analyze the effect of anti‐viral combinations on long‐term renal function based on the usual nephropathy risk factors.

Table 1.

Disclosures:

Hélène Fontaine ‐ Board Membership: Abbvie, Gilead, BMS, Janssen; Independent Contractor: gilead, BMS, MSD, Roche, Janssen

Jean‐Jacques Boffa ‐ Advisory Committees or Review Panels: MSD, Otsuka

Philippe Mathurin ‐ Board Membership: MSD, Janssen‐Cilag, BMS, Gilead, Abvie, Verlyx; Consulting: Roche, Bayer

Fabrice Carrat ‐ Grant/Research Support: ANRS Linda Wittkop ‐ Speaking and Teaching: Janssen, Gilead

The following people have nothing to disclose: Eric Thervet, Vincent Bonnemains, Laurent Alric, Bénédicte Stengel, Stanislas Pol

¹Liver Diseases Unit, Vall d'Hebron Research Institute, Barcelona, Spain; ²Departments of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain; ³Liver Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain; ⁴Centro de Investigation Biomédica en Red de Enfermedades Hepâticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain; ⁵Centro de Biologia Molecular Severo Ochoa (CSIC‐UAM), Consejo Superior de Investigaciones Cientificas, Madrid, Spain

Background Since the development of direct acting antivirals (DAAs), sustained virologic response (SVR) rates in chronic Hepatitis C patients have increased dramatically with DAAs combination therapies. However, the presence of resistance‐associated substitutions (RAS) with decreased susceptibility to DAAs within the viral quasispecies prior to therapy is considered as the main responsible of treatment failure and viral relapse. Currently, testing for RAS prior to first‐line DAA therapy is only recommended by clinical guidelines, for GT 1a patients (−Q80K) in Simeprevir based regimens and Elbasvir‐based treatment. In the present work we have analyzed the baseline prevalence of NS5A RAS among 1a and 1b treatment naïve patients in our geographic area by massive parallel sequencing using 454/GS‐Junior platform. Methods A total of 50 samples from treatment naïve chronic HCV patients have been selected, 18 G1a and 32 G1b.A fragment of 437nts of NS5A region have been amplified and sequenced using 454/ GS‐Junior sequencing platform and compared to consensus sequences provided by Los Alamos Sequence Database The cutoff of detection was 1%. The following RAS mutations have been considered in the present study: G1a (M28, L31, H58, E62, Y93) and G1b (L28, R30, L31, P58, Y93). Results Overall, RAS at NS5A regions have been detected in 50% of G1 patients (44% G1a and 53% G1b). 16.7% G1a and 28.1% G1b patients present RAS with frequency above 15%. The most prevalent RAS in G1a was m28v/t followed by H58R, L31M and Y93H. For subtype 1b the most prevalent substitution was Y93H followed by R30H/Q, L31M and P58S. The frequency of RAS ranged from 0.47% to 99.57% in G1a patients and from 0.44% to 100% in G1 b Interestingly, 11.1 % of G1a and 28.1% of G1b patients have Y93H substitution at baseline, which has been associated with reduced susceptibility to Daclatasvir, Ledipasvir and Ombitasvir. In G1a samples Y93H is observed as a minority mutant while in G1b, 22% of the Y93H carriers showed the mutation in 100% of sequences. Conclusions High‐resolution HCV‐sequencing technology is a good tool to study RAS. This methodology reveals a high prevalence of RAS in NS5A region in Spain, however, the clinical significance of each variant is dependent of the frequency and the type of RAS, and in this sense, Y93H has shown higher level of DAA resistance than other substitutions. Besides, here we show that the prevalence of each RAS is subtype‐dependent, and for instance Y93H is more prevalent in subtype 1b compared with 1a. It is still unknown which is the minimal frequency at which a minority RAS is clinically relevant.

Disclosures:

Maria Buti ‐ Advisory Committees or Review Panels: Gilead, Janssen, MSD; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, BMS

Rafael Esteban ‐ Speaking and Teaching: MSD, BMS, Novartis, Gilead, Glaxo, MSD, BMS, Novartis, Gilead, Glaxo, Janssen

The following people have nothing to disclose: Qian Chen, Maria Eugenia Soria, Josep Gregori, Celia Perales, Francisco Rodriguez‐Frias, Damir Garcia‐Cehic, Maria Homs, David Tabernero, Leonardo Nieto, Juan I. Esteban, Josep Quer

Ochsner Health System, New Orleans, LA

Introduction: Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States and accounts for significant morbidity and mortality. There have been increasing efforts to perform birth cohort screening to get this high risk group diagnosed and treated for HCV. It is usually reported that 75‐85% of people exposed to HCV develop chronic infection. Our group conducted a study to determine if the traditionally reported rates of developing chronic HCV are consistent with rates of chronic HCV we see in the era of birth cohort screening. Methods: Our health system consists of 15 hospitals and 63 health centers. The electronic medical record, Epic, was integrated into the entire health system by January 2014. Therefore, from January 2014‐ June 2016 we have been able to collect data on all patients within the health system born between 1945‐1965 who have been screened for HCV with HCV antibody (Ab) testing. We then identified those who were tested for HCV RNA. We calculated the percentage of patients HCV Ab+, then calculated the percentage of patients HCV RNA+. Results: In 2014, there were 20,171 patients who were screened for HCV, of which 968 (4.8%) tested positive. There were 778 (80.4%) patients with HCV RNA tests, of which 495 (63.6%) tested positive for chronic infection. In 2015, there were 21,053 patients screened for HCV, of which 1,092 (5.2%) tested positive. There were 634 (58.1%) patients with HCV RNA tests, of which 367 (57.9%) tested positive. In the first 6 months of 2016, there were 9,070 patients who were screened for HCV, of which 414 (4.6%) tested positive. There were 174 (42.0%) patients with HCV RNA tests, of which 73 (42.0%) tested positive. Conclusion: Based on our large health system 42‐64% of patients born between 1945‐1965 develop chronic HCV infection of those exposed to HCV; therefore, 36‐58% of patients exposed to HCV clear virus without treatment. This percentage of clearance is higher than the typically reported 15‐25% of patients who clear HCV without treatment. It is likely that spontaneous clearance of HCV is more common than previously expected.

Disclosures:

Gia Tyson ‐ Speaking and Teaching: Gilead Sciences

Shobha Joshi ‐ Grant/Research Support: Salix, Eisai; Speaking and Teaching: Merck, Gilead, Bristol‐Myers Squibb

George Therapondos ‐ Grant/Research Support: Gilead, Conatus; Speaking and Teaching: Grifols

Natalie H. Bzowej ‐ Grant/Research Support: Gilead Sciences, Ocera Therapeutics

Nigel Girgrah ‐ Speaking and Teaching: Gilead

The following people have nothing to disclose: Philip Oravetz, Susan Montz, Aldo Russo

¹Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA; ²Pathology, Stanford University, Stanford, CA

Background/Aim: With the advent of highly effective antiviral therapy against hepatitis C virus (HCV) infection, patients with decompensated cirrhosis are able to achieve sustained virologic response (SVR). There is widespread optimism that eradication of HCV would lead to reversal of cirrhosis, thus obviating the need for liver transplantation (LTx). Explants from LTx recipients present an opportunity to accurately assess histological changes of the liver after SVR in patients with already advanced liver disease. Methods: Institutional databases and medical records were reviewed to identify adult liver transplant recipients with HCV. Patients were divided into (1) SVR versus (2) non‐SVR groups, the latter being defined as viremia at the time of LTx Patients were stratified by presence of HCC Explant liver specimens were retrieved and reviewed by a single pathologist. Fibrosis stage, grade of inflammation, nodule size, and overall histological description were compared between the two groups. Results: Of the 349 adult patients who underwent LTx between 2011 and 2016, 149 had a primary diagnosis of HCV. 30 patients achieved SVR prior to LTx. Of the remaining patients (non‐SVR), 30 were selected and matched by age, MELD categories and year of transplantation. To date, five SVR explants have been reviewed and characterized completely (Table 1). All patients exhibited advanced, stage 4 fibrosis with varying degrees of inflammation (grade 0‐2) and nodule size, regardless of how recently they achieved SVR. The study is ongoing, and complete data in SVR and non‐SVR patients will be available at the time of presentation. Conclusion: Although the sample size to date is small, marked regression of cirrhosis was not observed. HCV patients with decompensated liver disease may have cirrhosis that is too far advanced to regress Complete analysis of the study samples may suggest that HCV therapy in LTx candidates should be individualized For some patients, postponement of antiviral therapy until post‐LTx may be advantageous, particularly in regions with a high median MELD score.

Table 1. Explant characteristics in 5 selected patients with HCV cirrhosis and SVR.

Disclosures:

W. Ray Kim ‐ Advisory Committees or Review Panels: Intercept, Gilead Sciences, Merck

The following people have nothing to disclose: Allison Kwong, John Higgins

CDE, Yale School of Public Health, New Haven, CT

Background: Approximately 5 million Americans live with hepatitis C virus (HCV) infection. Since 2010, the incidence of acute HCV infection is rising. Therefore, it is expected to observe an increase in HCV‐related morbidity and mortality, including cancer. Excess risk of liver cancer among HCV‐in‐ fected is well documented However, the excess risk of other extrahepatic cancers are less documented Of the extrahepatic cancers, non‐Hodgkin lymphoma, thyroid, pancreatic and multiple myeloma have been observed. Therefore, we examined risk of extrahepatic cancers as well as the possible mediating mechanisms among HCV‐infected subjects compared to non‐ HCV‐infected. Methods: The Surveillance, Epidemiology, and End Results (SEER) Medicare‐linked (SEER‐Medicare) database was used to assess cancer risk among 65 years and older in the United States. We used HCV ICD‐9 codes to classify subjects as HCV positive if their claims included any of the following: 070.41,070.44, 070.51,070.54, 070.70, 070.71, or V02.62 The study included 1,029,695 cancer cases as well as 100,000 frequency matched controls. We used unconditional logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CI) adjusting for the matching variables including age, sex, and calendar year For each cancer, we examined the cancer‐specific mediating mechanisms using structural equation modeling (SEM). Results: In the multivariable model, individuals with HCV infection had higher likelihood of overall cancer [OR (95% CI); 1.39 (1.23, 1.57)], lip cancer 2.00 ( 1.05, 3.80), stomach 1.33 ( 1.04, 1.72), anorectal 2.20 ( 1.30, 3.72), intrahepatic cancers 3.21 ( 1.90, 5.44), NHL 1.46 ( 1.22, 1.75), acute myeloid leukemia 1.64 ( 1.15, 2.33), non‐epithelial skin cancer 1.73 ( 1.05, 2.84), and pancreatic cancer 1.36(1.09‐1.69). Diabetes was the main mediator through which HCV infection might operate Other mediators included pancreatitis for pancreatic cancer and peptic ulcer for stomach cancer. Conclusion: HCV is a potential risk factor for several inflammation‐related and immune‐related types of cancer. The associations of HCV infection and cancers are partially mediated by diabetes, and other cancer‐specific factors such as pancreatitis and peptic ulcer. Further studies are needed to identify the mechanisms by which HCV infection may induce extrahepatic cancers.

Disclosures:

The following people have nothing to disclose: Fatma M Shebl

¹Infectious Diseases Unit, Massachusetts General Hospital, Boston, MA; ²Harvard Medical School, Boston, MA; ³Biostatistics Center, Massachusetts General Hospital, Boston, MA; ⁴Department of Medicine, Massachusetts General Hospital, Boston, MA; ⁵Division of Hepatology, University of Cape Town, Cape Town, South Africa

Background: Liver fibrosis stage determines clinical outcomes from chronic HCV infection. Those who achieved sustained virologic response (SVR) with interferon‐based therapies had

regression of fibrosis over time. This study aimed to assess the effect of HCV DAA therapy on changes in liver fibrosis, using transient elastography (Fibroscan). Methods: Patients being treated with DAA therapy for chronic HCV were enrolled in this prospective cohort study. We performed pre‐treatment baseline Fibroscans, then repeat scans at end of treatment (EOT) and 12 months post‐treatment. The primary outcome was significant improvement in liver fibrosis (>30% decrease in Fibroscan score 12 months after treatment), relative to baseline Multivariable logistic regression analysis was used to control for confounding. Signed rank test was used to assess change in liver stiffness measurement (LSM) between time points. Results: Of the 47 patients who have completed the protocol, 27 (57.4%) had significant baseline liver fibrosis (LSM >7.3 kPa), and 27 (57.4%) were treatment‐experienced. SVR rate was 95.7%. The primary outcome of >30% improvement in LSM was met in 24 (51.1%) patients. The 2 relapsers did not reach this outcome. Of those with baseline Metavir stage ≥F3 (LSM >8.5 kPa), 9/23 (39.1%) improved to <F2 (LSM ≤7.3 kPa) (cutoffs from reference 1). Baseline LSM >7.3 kPa was associated with reaching the primary outcome, and remained significant after controlling for BMI and elevated ALT (OR=8.8; 95% CI 1.9‐37.2). In this subgroup (baseline LSM >7.3 kPa), median intra‐patient change in LSM between pre‐treatment and 12 months post‐treatment was −4.5 kPa (IQR −7.1, −2.0; P<0.0001). Conclusions: Treatment of chronic HCV with DAAs leads to clinically relevant reduction in liver fibrosis over the first year post‐treatment, measured by Fibroscan, even after controlling for BMI and elevated ALT. This outcome was more likely in those with baseline significant liver fibrosis, with some experiencing improved Metavir fibrosis stage. Reference: 1. Tapper EB, Castera L, Afdhal NH. Clin Gastroenterol Hepatol 2015;13:27‐36.

Disclosures:

Gregory K. Robbins ‐ Grant/Research Support: Gilead, Xbiotech

Raymond T. Chung ‐ Grant/Research Support: Gilead, Mass Biologics, Abbvie, Merck, BMS

The following people have nothing to disclose: Justin Chan, Neliswa Gogela, Hui Zheng, Sara Lammert, Tokunbo Ajayi, Zachary Fricker, Arthur Y. Kim

Gilead Sciences, Foster City, CA

Background: Patients with chronic hepatitis C virus (HCV) infections and advanced chronic kidney disease (CKD) have faced substantial barriers to treatment. There are limited data on current HCV treatment patterns with direct‐acting antiviral (DAA) therapies in patients with HCV and advanced CKD. We examined US administrative claims data to characterize treatment uptake among patients with HCV and advanced CKD in the DAA era. Methods: All patients with chronic HCV and a claim for advanced CKD (stages IV or V or end stage renal disease) enrolled between January 2010 and March 2015 were included Differences in the treated and untreated advanced CKD populations at baseline (i.e. prior to or up to one year following first HCV claim) were analyzed by chi‐square tests. The proportion of advanced CKD patients initiating treatment and the distribution of treatment regimens was examined per calendar year for 2012‐2014. Results: 179,804 adult patients with chronic HCV were identified, of which 15.2% received any anti‐HCV treatment during the observation period. 3.3% of total HCV patients (N=5857) had a diagnosis of advanced CKD; most were between the ages of 45 and 64 years (75.7%) and male (69.5%), and 41.6% had a claim for dialysis at baseline. 9.3% of advanced CKD patients (N=545) ever received anti‐HCV treatment; of these, 303 had an advanced CKD claim prior to treatment start. Compared to untreated advanced CKD patients, advanced CKD patients treated for HCV were more likely to be under 65 years of age, male, and have a diagnosis of cirrhosis; and were less likely to have diagnoses of anemia or type 2 diabetes or to have received dialysis at baseline Treatment uptake and median duration by year is shown below. In 2012 and 2013, the most common regimens among treated advanced CKD patients were ribavirin (RBV) + interferon (IFN) (2012: 50.0%; 2013: 39.0%) and tel‐ aprevir + RBV + IFN (2012: 25.0%; 2013: 17.1%). In 2014, 92.4% of treated patients received a sofosbuvir (SOF)‐containing regimen, including SOF + simeprevir (35.3%), SOF + RBV (22.9%), and ledipasvir/SOF (18.2%). Conclusion: A growing number of patients with chronic HCV and advanced CKD are treated for HCV despite recognized treatment limitations in this population. Treatment uptake has increased with greater availability of DAAs, with the majority of treated patients receiving SOF‐based regimens in 2014.

Disclosures:

Amanda W. Singer ‐ Employment: Gilead Sciences

Brian L. McNabb ‐ Consulting: DocMatter; Employment: Gilead Sciences Inc.

Anu O. Osinusi ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Marcus Littman ‐ Employment: Gilead Sciences, Inc. ; Management Position: Gilead Sciences, Inc. ; Stock Shareholder: Gilead Sciences, Inc.

Anne‐Ruth van Troostenburg de Bruyn ‐ Consulting: King's College London; Employment: Gilead Sciences International Ltd; Stock Shareholder: Gilead Sciences

Anand P Chokkalingam ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

¹Gastroenterology and Hepatology, CHU de grenoble, Grenoble, France; ²CRI INSERM U‐823, Grenoble, France; ³Statistiques, CHU de creteil, Creteil, France; ⁴Biochimie, CHU de Grenoble, Grenoble, France; ⁵CIC 1406 INSERM, Grenoble, France; ⁶Universite Grenoble Alpes, TIMC‐Imag UMR 5525, Grenoble, France; ⁷ANRS, Paris, France

There are no specific marker predicting the development of any complication in patients with Child‐Pugh A post hepatitis C cirrhosis, sustained virological response excepted. The aim of the study was to analyze the place of surrogate markers of fibrosis in a french national multicenter prospective cohort of HCV‐infected patients with biopsy‐proven cirrhosis (ANRS CO12 CIRVIR) included in 35 centers in order to predict the development of complications especially HCC This study was a case control study ratio (1/4), the main events were collected on a 36 month period and were HCC, ascites, digestive hemorrage. Actitest‐Fibrotest, Fibrometer 3G, performed independently in one lab, and fibroscan were analysed every 6 months between months 0 to 36. Our multivariate analysis took into account confounding factors, matching and changes in markers with time (conditional logistic regression and mixed‐effects model). We included 136 cases (74/136 had HCC) and 270 controls (cirrhotic patient without any liver related events). In all groups mean age was 58±10 years, 65% were males The 2 groups were comparable for comorbidities (diabetes, kidney failure, HA, dyslipidemia) and all viral factors, except for SVR (66.8% vs 29.1%, p <0.001), and lab data (bilirubin, gammaGT, platelets, TP). Results were systematically adjusted on SVR. From D0 onwards, a significant difference between cases and controls was systematically found for the mean marker scores and persisted between D0 and M36: Fibrotest: 0.72±0.18 vs 0.84±0.10; Fibrometer 3G (fibrosis: 0.72±0.13 vs 0.94±0.06, 0.85±0.13 vs 0.94±0.06; ); and FibroScan: 17.0±11.2 vs 22.5± 12.8 (p<0.0001). This significant difference was found in SVR patients except for Fibroscan. The kinetics between D0 and M36 showed few clinically relevant changes, thus multivariate exploration of the predictive value of the tests was carried out for D0 After adjusting for SVR, all markers remained associated with the occurrence of a complication To conclude, all surrogates markers of fibrosis are able to early predict the occurrence of complications especially HCC in patients with post hepatitis C cirrhosis Markers kinetic do not give any additional information We hereby propose to monitor more accurately patients with high initial values, threshold remaining to be determined.

Disclosures:

Jean‐Pierre H. Zarski ‐ Advisory Committees or Review Panels: Roche, Scherring Plough, BMS, Gilead, Novartis, Janssen Cilag, Roche, Scherring Plough, BMS, Novartis, Janssen Cilag; Consulting: Gilead; Speaking and Teaching: Siemens Marie Noelle Hilleret ‐ Speaking and Teaching: BMS, GILEAD, ABBVIE Françoise Roudot‐Thoraval ‐ Advisory Committees or Review Panels: Roche, gilead; Consulting: LFB biomedicaments; Speaking and Teaching: gilead, Janssen, BMS, Roche, Abbvie

The following people have nothing to disclose: Sandra David‐tchouda, Candice Trocme, Jennifer Margier, Carole Cagnot, Pierre Nahon

Medicina Interna ed Epatologia, Universita degli studi di Salerno, Salerno, Italy

Introduction: Brachial Flow Mediated Dilation (FMD) is a well‐ known non‐invasive method to assess endothelial function. In chronic liver disease, endothelial function was shown impaired suggesting a significant correlation among liver damage, sinusoidal endothelial function and liver stiffness. Aim and Methods:To investigate the relationship between endothelial function and liver stiffness we performed a cross‐sectional study including 100 consecutive HCV Genotype 1 patients who underwent a complete clinical and laboratory screening for HCV infection. Liver stiffness was assessed by transient‐elastography (TE). FMD and Carotid Intima‐Media Thickness (c‐IMT) were evaluated by 2‐d ultrasound. Mean age was 62±12,5 years and 41,8% were woman Based on TE score and according to liver fibrosis (Metavir score) patients were grouped as it follows: F0:14%; F1:19%; F2:10%; F3:20%; F4:37%. Results show a significant inverse linear correlation between FMD and TE until the value of 20kPa of stiffness (p<0,001). For TE higher than 20kPa the correlation shown not significant although the tendency of FMD enhancement was of note. In the whole population with Spearman test, FMD was inversely correlated with TE (p<0.001), age (p=0.002), male sex (p=0.002), GGT (p=0.035), low PLT (p=0.001), APRI (p<0.001), c‐IMT (p=0.003) and directly with unconjugated bilirubin (p=0.014). At the multivariate regression analysis only TE (p<0.001), c‐IMT (p=0.003) were inversely, and unconjugated bilirubin (p=0.031) directly, associated with FMD Further sub analysis was conducted in patients with TE>20kPa (n=30) and <20kPa (n=70). In patients with TE>20 kPa at the multivariate analysis only unconjugated bilirubin (p=0.031) and low albumin (p=0.012) were directly correlated with FMD. While in the group with TE <20 kPa the only independent factors inversely associated with FMD were TE (p=0.017) and c‐IMT (p=0.001). In conclusion an impaired FMD is significantly associated to a worst TE in chronic HCV related hepatitis In patients with sickest disease, the liver failure, surprisingly, seems to be associated with a reconstituted endothelial function

Disclosures:

Marcello Persico ‐ Advisory Committees or Review Panels: abbvie; Grant/ Research Support: gilead

The following people have nothing to disclose: Tommaso Bucci, Mario Masarone, Andrea Aglitti, Rosa Caruso, Pasqualina Di Siervi, Marie Francoise Tripodi

¹School of Osteopathic Medicine, Campbell University, Buies Creek, NC; ²Fayetteville Gastroenterology Associates, Fayetteville, NC; ³Mathematics and Computer Science, Fayetteville State University, Fayetteville, NC

Introduction‐ Evidence indicates that patients with chronic hepatitis C (CHC) have an increased risk of neoplasia. Data from tertiary referral centers suggests that HCV may be an independent risk factor for colonic neoplasia However, the link between colon cancer and CHC in a community setting has not been extensively studied. Goal‐ The goal of this study was to determine if patients with CHC undergoing colonoscopies have an increased risk of colonic neoplasia. Methods‐ Colonoscopy data were retrospectively collected and compared for patients with CHC and controls who underwent screening (N=370) and surveillance (N=126) between 1993 and 2016. Patients were matched for age, sex, and race. Data based on polyp size and histology was collected. Regression analysis was applied. Results‐ The screening data consists of 185 patients with CHC and 185 non‐hepatitis controls. The surveillance data consists of 67 CHC and 59 patients without chronic liver disease. Analysis of screening data indicated that patients with CHC had a greater number of adenomas in comparison to controls (70% vs 45%; p<0.001, respectively). A trend towards advanced neoplasia was seen in the CHC group (8% vs 4%; p<0.15). Patients with CHC had a greater number of polyps larger than 0.75 cm in comparison to controls (31% vs 19%; p< 0.05, respectively) Regression analysis indicated the independent risk factors of CHC and male sex for the development of colonic neoplasia The odds of having polyps in CHC patients was 55% higher than the odds of having polyps for controls (odds ratio 3.55, 95% confidence interval [CI]: 2.16, 5.94). For the surveillance data, the total number of patients with polyps was higher in the CHC group than controls (70% vs 47%, p<0.05) There was a higher proportion of patients with tubular adenomas in the CHC group. (61% vs 46%, p=0.12). There was a trend for patients with CHC having polyps larger than 0.75 cm in comparison to controls (25% vs 19%, p=NS). For surveillance data, regression analysis revealed CHC as an independent risk for the development of colonic neoplasia. The odds of having polyps for CHC patients were 227% higher than the odds for control patients (odds ratio 3.27, 95% CI: 1.37, 8.25). Conclusion‐ This study concludes an association between HCV infection and increased numbers of polyps and more advanced neoplasia in patients undergoing screening colonoscopy. CHC patients undergoing surveillance had a greater odds of polyp formation than controls Further research should determine if this high risk population should undergo screening at an earlier age and/or at decreased intervals.

Disclosures:

The following people have nothing to disclose: Matthew Conti, John E. Poulos, Valentin Milanov

¹Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan; ²Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ³Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Background: Recently, a novel glycobiomarker Wisteria floribunda agglutinin+ ‐ Mac‐2 binding protein (M2BPGi) has been available for evaluation of liver fibrosis The aim of this study was to assess the association between serum M2BPGi level and 1) progression of fibrosis and hepatocarcinogenesis, and 2) cumulative survival rate and carcinogenesis rate in patients with hepatitis C virus (HCV) Methods: This study protocol was approved by the appropriate institutional ethics review committees. Serum M2BPGi levels were measured by HISCL M2BPGi (Sysmex Co., Japan) from 128 HCV‐infected patients who were histopathologically diagnosed as F3 or F4 in our hospital from January 1998 to August 2014. All F4 patients were diagnosed as Child‐Pugh Class A. The numbers of F3 or F4 patients were 44 (non‐hepatocellular carcinoma [HCC]/ HCC=30/14) and 84 (non‐HCC/HCC=49/35), respectively. The median age was 65 (29‐85) and male was 74 (57.8%). Seventy‐nine patients without HCC at baseline were analyzed for survival and carcinogenesis rates during a median of 51 months (1‐195). For statistical analyses, chi‐square test or Mann‐Whitney U test were used. Both cumulative survival rate and carcinogenesis rate were calculated by the KaplanMeier method. Results: 1) Serum M2BPGi levels (C. O. I) were significantly higher in patients with F4 (non‐HCC/HCC=7.2 [0.9‐19.3]/7.0 [0.5‐39.2]) than F3 (non‐HCC/HCC= 2.0 [0.5‐14.0] /3.5 [1.0‐8.4]) (p<0.001). In F3 and F4, serum M2BPGi levels did not differ significantly between patients with HCC and without HCC 2) In F3 or F4 patients without HCC (n=79), five/eight years survival rates of high M2BPGi group (≥4, n=39) were 78%/48%, respectively, whereas those of intermediate M2BPGi (1‐4, n=33) were 100%/82%, respectively. No one died in patients with low M2BPGi (<1, n=7). The survival rate differed significantly among the three groups (p=0.0041). HCC incidence in patients with high M2BPGi was higher than in those with low M2BPGi (p=0.0019). Cumulative carcinogenesis rates in patients with high M2BPGi were 48.7% after 4 years, contrasted with 16.9% in patients with intermediate M2BPGi and 0% in patients with low M2BPGi. The cumulative carcinogenesis rate differed significantly among the three groups (p = 0.002). All of the 7 patients without HCC who died within 60 months were diagnosed as F4 with high M2BPGi (16.3 [7.7‐18.9]), and the period before dying was 29 months (3‐58). Conclusions: Serum M2BPGi is useful for diagnosis of F4 despite the existence of HCC, and the patients with high M2BPGi had poor prognosis. Assessing serum M2BPGi would be diagnostic utility for predicting carcinogenesis and survival in patients with advanced fibrosis.

Disclosures:

Yasuhito Tanaka ‐ Grant/Research Support: Chugai Pharmaceutical CO., LTD., MSD, abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Bristol‐Myers

Squibb

The following people have nothing to disclose: Takako Inoue, Yuji Tsuzuki, Etsuko Iio, Kumiko Ohne, Noboru Shinkai, Tomoyuki Ohike, Takaaki Goto, Shigeru Sato

¹Ogaki Municipal Hospital, Ogaki, Japan; ²Hiroshima Univiersity, Hiroshima, Japan

Background & Aims Eradication of hepatitis C virus (HCV) by interferon (IFN)‐based therapy has been reported to reduce all‐cause mortality rates in patients with chronic HCV (CHC) infection. However, the impact of HCV eradication on nonliver‐related mortality including the causes of death has not been sufficiently investigated in CHC patients with advanced liver fibrosis Methods We enrolled 784 CHC patients with advanced liver fibrosis (APRI>1). Causes of death, incidence of hepatocellular carcinoma (HCC), and all‐cause mortality including non‐liver‐related diseases, were analyzed Results Of these 784 patients, 170 achieved sustained virological response (SVR) (eradication of HCV) by IFN‐based therapy (IFN‐SVR) or 614 did not receive IFN‐based therapy (non‐IFN patients) (Cohort 1); of these, 130 were selected from IFN‐ SVR (n=65) and non‐IFN (n=65) groups using propensity score matching (Cohort 2) The median follow‐up duration was 10.3 years In Cohort 1 patients, mortality rates from non‐liver‐related diseases were 63.6% (7/11) in IFN‐SVR patients and 36.3% (95/262) in non‐IFN patients, respectively. In Cohort 2 patients, mortality rates from non‐liver‐related diseases were 66.7% (2/3) in IFN‐SVR patients and 56.0% (14/25) in non‐ IFN patients, respectively. The eradication of HCV reduced all‐cause mortality (hazard ratio (HR), 0.105; 95% confidence interval (CI), 0.032‐0.349) including non‐liver‐related mortality (HR, 0.147; 95% CI, 0.034‐0.635), and the incidence of HCC (HR, 0.195; 95% CI, 0.083‐0.454). Conclusions Eradication of HCV reduced not only liver‐related mortality but also non‐liver‐related mortality in CHC patients with advanced liver fibrosis.

Disclosures:

The following people have nothing to disclose: Toshifumi Tada, Takashi Kumada, Hidenori Toyoda, Natsuko Kobayashi, Junko Tanaka

¹Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM; ²Mathematics & Statistics, University of New Mexico, Albuquerque, NM; ³Department of Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA; ⁴Medicine, University of California‐San Francisco School of Medicine, San Francisco, CA; ⁵Department of Epidemiology & Biostatistics, University of California San Francisco, San Francisco, CA

Sharing needles and ancillary injection drug equipment places people who inject drugs (PWID) at risk for hepatitis C virus (HCV), a highly infectious blood‐borne infection. The availability of data on HCV infectivity in the context of injecting with another person's previously used needle is limited. Our goal was to estimate the per‐contact probability of HCV infection and reinfection accompanying injection with previously used needles, classified as receptive needle sharing (RNS). A probabilistic exposure model linking observed HCV infection outcomes to self‐reported RNS exposure was applied to data from the UFO Study, a prospective observational cohort study of 784 active PWID under age 30 who were surveyed and tested quarterly for HCV between 2003‐2008 and 2010‐2014 in San Francisco, California For each participant, the first survey with an HCV‐negative status up through the first survey with an HCV‐positive status was selected, returning 118 participants in the analysis. A maximum likelihood estimate considering RNS yields a per‐contact HCV infectivity ranging between 0.89% and 1.62% among HCV susceptible groups. Table 1 shows the per‐contact probability of HCV (and 95% bootstrap confidence intervals) among the different susceptible groups who became infected or reinfected at least once. The strengths of this study include the ability to assess infectivity specifically from data on receptive needle sharing contacts (vs. 'sharing needles'), as well as the short (3‐month) recall and HCV testing periods to ascertain these exposure and outcome events These factors likely account for the higher infectivity estimates than found by others of 0.57% (95% CI 0.32%, 1.05%) (Boelen et al. 2014). This analysis fills an important gap in information due to its focus on per‐contact probability of HCV in association with RNS, a primary route of HCV transmission among PWID. Results can inform models and research on the impact of prevention scale up and population level impact. Reducing RNS and frequency of RNS will contribute to reducing the spread of HCV.

Per‐contact probability of HCV acquisition associated with RNS

Disclosures:

Kimberly Page ‐ Grant/Research Support: NIH, Gilead, CDC

The following people have nothing to disclose: Yuridia Leyva, Stephen Shiboski, Judith A. Hahn, Jennifer Evans, Erik Erhardt

¹Biological Sciences, University of Southern California, Los Angeles, CA; ²Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, TX; ³Aerospace and Mechanical Engineering, University of Southern California, Los Angeles, CA

Background Approximately 2‐6% of hepatitis C virus (HCV) patients with cirrhosis will develop hepatocellular carcinoma (HCC) in their lifetime. The aspartate aminotransferase to platelet ratio index (APRI) score is a non‐invasive measure of fibrosis that can be used to determine the risk of advanced liver disease. While APRI scores can fluctuate over the course of the disease and appear random, we explored the possibility that specific patterns can be used as diagnostic measures in certain groups of HCV patients. Methods Using the Veteran Health Administration HCV Clinical Case Registry, we isolated a set of 34,268 HCV patients (17,134 HCV antibody+ and RNA+ cases propensity matched to 17,134 HCV antibody+ and RNA‐). Patients were required to have a minimum of two APRI scores in separate years and no prior existing evidence of cirrhosis or HCC. For each year in the study, we classify each patient using lab data based on their median APRI score in that year or ICD‐9 code into 8 clinical stages including APRI: 0‐1, APRI: 1‐1.77, APRI: > 1.77, compensated cirrhosis, decompensated cirrhosis, HCC, transplant (post‐transplant care), and death. Data and models are analyzed on a webpage that has the capability of displaying multiple interactive figures of patient subgroups (e g age, race, gender, alcohol abuse, etc ) for side‐by‐side comparisons Results Based on the defined stages recorded in each year, we illustrated disease progression for the population as tree ring diagrams spanning a 14 year period, overall and by subgroups For example, we analyzed age groups of 20‐49, 50‐64, and 65‐100 y/o and observed that while many of the older population died early on in the study, the middle population had more distinct pathways (304 paths compared to 218 in the younger and 157 in the older) Based on these stage progression paths, we created Markov chain models that are used to run Monte Carlo simulations to simulate HCV progression to advanced liver disease. We found that the younger population had greater probabilities of fluctuating APRI scores before progression to advance liver disease, and that this can be used as a measure to predict future outcomes. Conclusions APRI scores are a powerful diagnostic tool for measuring progression to advanced liver disease, and the patterns that emerge in fluctuating scores are easily viewed as tree ring diagrams. Modeling this progression as a Markov process provides a unique and novel way of predicting future liver disease outcomes in HCV patients. By more accurately predicting these outcomes in specific patient groups, we can ultimately improve HCV patient care and reduce costs associated with unnecessary treatments.

Disclosures:

Peter Kuhn ‐ Stock Shareholder: Epic Sciences

Jennifer R. Kramer ‐ Grant/Research Support: Gilead Sciences

The following people have nothing to disclose: Jeremy M. Mason, Peter Richardson, Fasiha Kanwal, Paul K. Newton

¹Department of Social Work; Department of Health Behavior; Center for AIDS Research; Comprehensive Center for Healthy Aging, The University of Alabama at Birmingham, Birmingham, AL; ²Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL; ³Department of Epidemiology; Department of Emergency Medicine; Comprehensive Cancer Center, The University of Alabama at Birmingham, Birmingham, AL; ⁴Division of Gastroenterology & Hepatology, The University of Alabama at Birmingham, Birmingham, AL

BACKGROUD AND AIMS: Geospatial analysis is a novel epidemiologic approach that can be used to identify and map geographic disease cluster areas and describe demographic characteristics of those areas. There are scant studies on the use of geospatial analysis in hepatitis C (HCV) research. We sought to determine the geographic distribution of HCV‐related cirrhosis cases by Alabama three‐digit zip codes, and determine patient‐level and community‐level factors associated with higher HCV‐related cirrhosis rates METHODS: We obtained data from 738 HCV‐infected patients who presented for care at UAB's Liver Center from January 2015 through December 2015. We performed three‐geospatial analysis: Empirical Bayes [EB], Local Moran's I [LISA], and Getis Ord Gi* [Gi*]. We considered three‐digit zip code areas to be “Clustered” if they were identified as high risk or cirrhosis hot spots using two or more of the geospatial metrics (i. e., LISA, Gi*, or EB rates). All other three‐zip code areas were classified as “Non‐Clustered”. RESULTS: The prevalence of HCV‐related cirrhosis was 33% (247/738). There were a total of 88 HCV‐related cirrhosis cases within the Clustered areas, and 159 cases within the Non‐Clustered areas The cirrhosis Clustered region had a higher cirrhosis event rate (9.40 per 100,000 persons; 95% CI: 7.60 ‐ 11.50) compared with the Non‐Clustered (4.10 per 100,000 persons; 95% CI: 3.50 ‐ 4.80). The Clustered communities were located in central Alabama with the city of Birmingham at the centroid point of the strong cirrhosis clustering Event rates for the 350 (10.40 per 100,000 persons; 95% CI: 7.80 ‐ 13.90) and 352 (8.50 per 100,000 persons; 95% CI: 6.30 ‐ 11.50) Birmingham zip codes were among the highest between Alabama three‐digit zip codes Patients who lived in cirrhosis Clustered communities were more likely to be of Black race (45.80% vs. 20.45%, p <0.01), report active drug use (13.99% vs. 10.40%, p = 0.05), and no tobacco use (43.01% vs. 32.96%, p < 0.01) when compared with patients who lived in the Non‐Clustered communities Clustered communities had higher education (p < 0.01) Non‐Clustered communities had a larger proportion of individuals living above the poverty threshold (21.85% vs. 19.80% for PIR 1 ‐ 2, 5.83% vs.5.53% for PIR >2, p <0.01) when compared with Clustered communities CONCLUSION: This study supports the use of geospatial analysis as a tool for identifying geographic distribution of HCV‐related cirrhosis hot spots. Future studies are needed to investigate underlying causes of non‐random cirrhosis clustering in the metropolitan Birmingham area.

Disclosures:

Mohamed G Shoreibah ‐ Advisory Committees or Review Panels: Gilead

The following people have nothing to disclose: Omar T Sims, Krishna V Venkata, Justin X. Moore, Sumant Arora, Omar I. Massoud

¹Population Health, Burnet Institute, Melbourne, VIC, Australia; ²Infectious Diseases, Alfred Health, Melbourne, VIC, Australia; ³Gastroenterology, St Vincent's Hospital Melbourne, Melbourne, VIC, Australia; ⁴Medicine, University of Melbourne, Melbourne, VIC, Australia

Background Fibrosis assessment prior to hepatitis C (HCV) treatment is recommended, however access to elastography is limited by resources in many settings, even in high‐income countries This study aims to assess whether routine blood tests can be used to triage need for non‐invasive fibrosis assessment in a community‐based cohort of people who inject drugs (PWID). Methods The HCV Treatment And Prevention (TAP) Study examines the feasibility of community‐based HCV treatment for PWID using oral sofosbuvir/ledipasvir ±ribavirin in Melbourne Haematological, biochemical and fibrosis assessment using transient elastography (FibroScan™) were performed at screening The AST:Platelet Ratio Index (APRI) was calculated and compared with valid FibroScan scores (10 readings >60% success; <30% IQR/median) at screening. Cirrhosis (Ishak F4) was defined as FibroScan score ≥12.5 kPa. Negative (NPV) and positive predictive values (PPV) were calculated for predicting cirrhosis at high (2.0) and low (1.0) APRI. Results Of participants screened to date, APRI was calculable in 114/118, and valid FibroScan was available among 99/114. Participants were 67% male, median age 37 years (IQR 33—44 years), with median body mass index 23.1 (IQR 20.9—26.4). Median APRI was 0.54 (IQR 0.29—0.98). Median FibroScan score was 5.6kPa (IQR 4.5—6.8kPa); 7% and 12% had liver stiffness ≥12.5kPa and ≥9.5kPa, respectively. Two individuals had discrepant APRI<1.0 and FibroScan>12.5kPa score: both were male, aged 32 and 35 years old, with BMI 27.5 and 22.5, and ALT 74U/l and 70U/l, respectively Using an APRI cut off of 1.0, NPV for cirrhosis was 96% (70/73; 95%CI 89—99%), and PPV was 19% (5/26). Using an APRI cut off of 2.0, NPV for cirrhosis was 94% (88/94) and PPV was 40% (2/5). Conclusions A low APRI score (<1.0) may be an acceptable community screening test to exclude cirrhosis where FibroScan is unavailable. Use of APRI may facilitate treatment initiation in such settings APRI threshold >1.0 should not be used to diagnose cirrhosis.

Disclosures:

Joseph S Doyle ‐ Grant/Research Support: Gilead Sciences, Bristol‐Myers Squibb, Abbvie

David M. Iser ‐ Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck, Roche

Amanda J Wade ‐ Grant/Research Support: AbbVie

Alex J Thompson ‐ Advisory Committees or Review Panels: Gilead, Abbvie, BMS, Merck, Spring Bank Pharmaceuticals, Arrowhead, Roche; Grant/Research Support: Gilead, Abbvie, BMS, Merck; Speaking and Teaching: Roche, Gilead, Abbvie, BMS

Margaret Hellard ‐ Grant/Research Support: Gilead Sciences, BMS, Abbvie

¹National Center for Global Health and Medicine, Ichikawa, Japan; ²Department of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus, Nishihara, Japan

BACKGROUND/AIM: The distribution of hepatitis C virus (HCV) genotypes varies according to ethnic and geographic differences in the world. HCV genotype 1b (GT‐1b) is the most prevailing type in Japan, while the prevalence of HCV GT‐1a is rare in the mainland of Japan. In contrast, Okinawa island, which is located in the south of Japan, has the history of US military occupation after the World War II. The prevalence of GT‐1a in Okinawa is reported to be higher than that in the mainland, the reasons of which may be influenced by geographical, historical and social backgrounds We aimed to elucidate the route and timescale of transmission of HCV GT‐1a by clarifying genetic features of HCV GT‐1a in Okinawa island using whole genome sequencing of HCV and subsequent phylogenetic analysis. PATIENTS/METHODS: In this study, 10 patients with HCV GT‐1a infection determined by serological test were enrolled, who were born and bred in Okinawa island (mean age, 58.4 years; 6 male and 4 female). We performed whole HCV genome sequencing covering the region from Core to NS5B using several pairs of primer. For phylogenetic analyses, the obtained sequence was aligned using MAFFT with a set of global references retrieved from HCV database Phylogenetic trees were constructed with 6‐parameter method and bootstrapped 1,000 times to confirm the reliability of the phylogenetic tree by Neighbor‐Joining method using MEGA v7. RESULTS: We successfully obtained full genome sequences of HCV GT‐1a from all of the samples. In phylogenetic analyses, these sequences were clustered into HCV GT‐1a group consisting of US strains but not Asian cluster, suggesting that a possible route of transmission was from US To estimate the epidemic period of HCV GT‐1a in Okinawa, we performed phylodynamic analysis using all samples. The time of spreading of HCV GT‐1a was estimated around the Viet Nam War. Several routes of HCV Gt‐1a infection were observed because a specific cluster consisting of Okinawa samples was not observed in the phylogenetic tree CONCLUSION: In Okinawa, HCV GT‐1a was estimated to be introduced from US, spreading of which was accelerated by the increase of intravenous drug users (IVDU) during Viet Nam War. In the present, as HCV infection risk via medical activity was exceedingly zero in Japan, educational activity to take a screening test for HCV infection patients was also needed to reduce chronic hepatitis C patients.

Disclosures:

The following people have nothing to disclose: Kunikazu Hoshino, Masaya Sugiyama, Tatsuji Maeshiro, Tomoko Date, Hirotaka Shoji, Yohei Mano, Hiroyoshi Doi, Sachiyo Yoshio, Tatsuya Kanto, Masashi Mizokami

¹Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Hospital, Beijing, China; ²Liver Failure Treatment and Research Center, 302 Hospital, Beijing, China; ³Division of Gastroenterology & Hepatology, Humanity & Health Medical Centre, Hong Kong, Hong Kong; ⁴State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China

Background and Aim In the era of direct‐acting antivirals (DAAs), sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC) are remarkably increased. However, whether DAAs therapies can improve liver histology is still largely unknown We aim to evaluate the impact of DAA therapies on liver fibrosis and cirrhosis non‐invasively by liver stiffness measurement (LSM). Methods One hundred and seventy‐five Chinese patients with genotype 1 CHC were included in this study, which were treated with pan‐oral DAAs for 12 weeks (Group 1), including ledipasvir (90 mg)/sofosbuvir (400 mg) (n=123), daclatasvir (60 mg)/sofosbuvir (400 mg) (n=50) and paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg) plus dasabuvir (250 mg) (n=2). Fifty‐five age and gender matched patients treated with long‐term pegylated interferon (PEG‐IFN) based therapies (median treatment duration: 60 weeks) were enrolled as the control group (Group 2) The median follow‐up duration for Group 1 and 2 were 44 weeks and 46 weeks respectively LSM was measured at baseline, the end‐of‐treatment and the end of follow‐up by transient elastography (TE). Advanced liver fibrosis or cirrhosis (F≥3) is defined by LSM>9.5 kPa. Results One hundred and seventy‐two patients in Group 1 (172/175, 98.3%) achieved SVR at the end of follow‐up, which was significantly higher than that of Group 2 (42/55, 76.4%) (p<0.001). Median LSM decreased significantly from baseline to the end‐of‐treatment in both groups (Group 1: 12.5 vs. 10.6 kPa, p<0.001; Group 2: 15.2 vs. 12.1 kPa, p<0.001). Median LSM also decreased significantly during the follow‐up in Group 1 (10.6 vs. 8.7 kPa, p<0.001), but not in Group 2 (12.1 vs. 13.2 kPa, p=0.378). The median LSM reduction from the baseline to the end of follow‐up in Group 1 was 1.8 kPa, which was equivalent to the median LSM reduction in Group 2 (2.4 kPa, p=0.08). In Group 1, there were 105 (60.0%) patients had advanced liver fibrosis or cirrhosis (F≥3) at baseline, which significantly reduced to 54.3% (95/175, p<0.001) at the end‐of‐treatment and further significantly reduced to 46.3% (81/175, p<0.001) at the end of follow‐up. Similarly, patients with advanced fibrosis and cirrhosis at baseline in Group 2 (41/55, 74.5%) were also significantly reduced to 61.8% (34/55, p<0.001) after PEG‐IFN treatment, but there is no significant change from the end‐of‐ treatment to the end of follow‐up (65.4%, p=0.378). Conclusion Liver fibrosis and cirrhosis significantly regressed during the treatment and follow‐up of DAA therapies in genotype 1 CHC patients The impacts of 12‐week DAAs therapies on liver stiffness were equivalent to long‐term PEG‐IFN treatment.

Disclosures:

The following people have nothing to disclose: Guofeng Chen, Dong Ji, Lei Lu, Yudong Wang, Jing Chen, Cheng Wang, Qing Shao, Bing Li, April Wong, Vanessa Wu, George Lau

¹Hepatology Department, Centre Hospitalier Universitaire d' Angers, Angers Cedex 9, France; ²Biochemistry, CHU, Angers, France; ³HIFIH laboratory, Angers University, Angers, France; ⁴Pathology, CHU, Angers, France

Fibrosis blood test construction is classically limited to a unique diagnostic target: significant fibrosis. Yet, these single‐target tests are commonly used for other diagnostic targets like cirrhosis. Therefore, our aim was to improve the accuracy of non‐invasive fibrosis staging by targeting biomarkers for all diagnostic targets using a new statistical method. Methods. 2589 patients were included: 1012 with chronic hepatitis C (CHC) in a derivation population and 1577 in 5 validation populations of different etiologies (CHC, chronic hepatitis B, HIV/CHC, NAFLD, alcoholic liver disease) using Metavir fibrosis stages (F) by liver biopsy as reference. FibroMeter biomarkers were statistically combined against as many fibrosis targets as made possible by Metavir staging. Several statistical functions were successively used to provide a unique score ranging from 0 to 1 as in classical fibrosis scores This new score was called multi‐target FibroMeter^V2G (MFM^V2G). Accuracy was evaluated primarily by the Obuchowski index discriminating all Metavir stages and secondarily by AUROCs for binary diagnostic targets and by correct classification rates in fibrosis classifications (into 6 fibrosis classes from F0/1 to F4). Results. In the derivation CHC population, the Obuchowski index (0.853) and AUROC for cirrhosis (0.929) of MFM^V2G were significantly superior to those of single‐target (F≥2) FibroMeter^V2G (0.843 and 0.907, respectively, p<0.001). MFM^V2G classification was more accurate (92.3%) than FibroMeter^V2G classification (87.6%, p<0.001). In the CHC validation population (641 patients), the Obuchowski index and AUROC for cirrhosis of MFM^V2G were significantly superior to those of all other single‐target classical blood tests: FibroMeter^V2G, CirrhoMeter^V2G, APRI, Fib4, Fibro‐ test, Hepascore and Zeng score. MFM^V2G was also globally superior to untargeted Fibroscan according to the Obuchowski index: 0.797 vs 0.766, respectively, but this was not significant (p=0.178). Similarly, their AUROCs for cirrhosis were not significantly different, MFM^V2G: 0.880, Fibroscan: 0.897, p=0.090 MFM^V2G classification remained more accurate (88.0%) than FibroMeter^V2G classification (83.6%, p<0.001). Most of these results were confirmed in other etiologies. Conclusion: Multi‐targeting biomarkers improves the accuracy of non‐invasive fibrosis staging in a highly significant manner compared to classical single‐target blood tests, matching liver elastography even for cirrhosis diagnosis.

Disclosures:

Paul Cales ‐ Consulting: Echosens Jerome Boursier ‐ Consulting: Echosens

Isabelle Fouchard‐Hubert ‐ Speaking and Teaching: ABBVIE, BMS, GILEAD The following people have nothing to disclose: Oberti Frederic, Valerie Moal, Sandrine Bertrais, Gilles Hunault, Marie Christine Rousselet

¹Department of Internal Medicine and Clinical Immunology, AP‐HP, Groupe Hospitalier Pitié‐Salpêtrière, Paris, France; ²Inflammation‐Immunopathology‐Biotherapy Department (DHU i2B), Sorbonne University, UMPC Univ Paris 06, UMR 7211, Paris, France; ³CEMKA, Paris, France

Background Accounting for the economic burden of extrahepatic manifestations is essential for a more accurate correct quantification of the benefits of treatment of HCV. HCV infection is the main cause of cryoglobulinemia vasculitis (CryoVas). Evolution in HCV treatment has allowed for changes in the management of CryoVas. Objective To estimate the effectiveness and costs of HCV‐CryoVas treatment in the direct acting antiviral (DAA) era and compare to those in the pre‐DAA era, in a tertiary national reference French center. Methods A chart review of HCV‐CryoVas patients treated from 1996 to 2015 was performed. Patients were divided in two groups according to the first HCV treatment (group 1: interferon (IFN) ± ribavirin (RBV) or pegIFN+RBV, group 2: HCV treatment with DAA). Main clinic‐biological characteristics were assessed at diagnosis, before and following the first anti‐viral session Effectiveness was evaluated in three dimensions: (1) Clinical response (CR) ‐ improvement of all or some of the organs affected by CryoVas at baseline, and the absence of clinical relapse, (2) Immunological response (IR) ‐ decrease >50% or the absence of cryoglobulinemia after treatment, (3) Sustained virological response (SVR) ‐ negative viremia post‐treatment. For cost analyses, all resources used for each patient were collected including HCV treatments, non‐viral drugs, dialysis, duration of hospitalizations and rehabilitation care for CryoVas. Results 201 patients with CryoVas were treated at the center since 1996. 107 (53%) women, mean age at CryoVas diagnosis 59 ± 13 years, F3/F4 Metavir score in 69 (37%), and main genotypes were 1 (64%), 2 (12%) and 4 (11%). Main CryoVas symptoms were neuropathy (76%), purpura (69%), arthralgia (50%), glomerulonephritis (33%), and sicca syndrome (10%), with a mean of 4.9 extrahepatic CryoVas manifestations per patient. Cryoglobulinemia was positive in 185 (92%), type 2 Ig Mk (72%), and at a mean level of 1.2 g/L. There were no statistically significant differences in baseline characteristics between the groups CR improved from 79% to 96%, IR from 77% to 89% and SVR from 43% to 75% HCV drug cost increased from 11,941 € to 57,669€, the mean total cost increased less (63,433€ to 90,377€) due to a decrease in both hospitalization costs (33,591 € to 21,347€), in non‐antiviral treatments (17,899€ to 11,397€). Conclusion In this large cohort of HCV‐CryoVas patients, improved antiviral effectiveness and safety of HCV drugs in the DAA era resulted in higher rates of clinical and immunological responses of CryoVas and a significant reduction in hospitalization and non‐antiviral treatment costs.

Disclosures:

Patrice P. Cacoub ‐ Advisory Committees or Review Panels: gilead, abbvie; Grant/Research Support: msd, bms; Speaking and Teaching: janssen

Antoine Lafuma ‐ Grant/Research Support: Genomic Health, GSK, Pierre Fabre MV©dicament, UCB, BMS, Bayer, Gilead, Biogen, Gedeon Richter, Urgo, Sanofi, Diaxonhit, Janssen, Insmed, CSL Berhing, Eisai, MSD

The following people have nothing to disclose: Mathieu Vautier, Anne Claire Desbois, Marianne Doz

¹Gastroenterology, Methodist Dallas Medical Center, Dallas, TX; ²Clinical Research Institute, Methodist Health System, Dallas, TX; ³The Liver Institute at Methodist Dallas Medical Center, Dallas, TX

Background Hepatic steatosis is the defining feature of non‐alcoholic fatty liver disease (NAFLD) and has been associated with chronic hepatitis C infection (CHC), particularly genotype 3. Both diseases are associated with liver fibrosis and cirrhosis Previous studies have suggested an association of higher degrees of steatosis in CHC patients with more advanced fibrosis. We aim to investigate how the prevalence of steatosis and non‐alcoholic steatohepatitis (NASH) have changed as obesity has become more prevalent and how their presence affects fibrosis in CHC. Methods We conducted a retrospective review of 857 patients who had native liver biopsy for CHC at a tertiary referral center between 2011‐2015. Repeat biopsies and those without evidence of CHC were excluded. Variables collected include age, sex, Batts‐Ludwig score, degree of steatosis, histologic features, BMI, HCV genotype, LFTs, platelet count, presence of comorbidities and alcohol abuse within 6 months of biopsy. Analysis was performed using STATA version 14 and SPSS version 21. Results Overall, 58.95% of patients had steatosis & 10.82% had steatosis >30%. 3.97% of the overall population had NASH Patients with NASH had a statistically significant higher prevalence of genotype 3 and elevated transaminases compared to those without NASH Additionally, Hispanics had a statistically higher prevalence of NASH(OR=3.50;95% CI=1.39‐8.50), but not steatosis, compared to other races There was no increased prevalence of genotype 3 infection for Hispanics. There was no difference in age, BMI, diabetes, hypertension, hyperlipidemia or CV disease The presence of steatosis was associated with higher rates of advanced fibrosis (OR = 1.98; 95% CI=1.432.76). High percentage of steatosis(>30%) (OR = 2.76; 95% CI=1.60‐4.77) and presence of SH (OR=2.94; 95% CI = 1.34‐6.64) were associated with higher rates of advanced fibrosis compared to those without steatosis Conclusions Steatosis is highly prevalent in those with chronic CHC. Coexistent NASH/ CHC existed in a small number of those undergoing biopsy, but higher rates of NASH/CHC are seen in Hispanics and those with genotype 3 Both steatosis and NASH are associated with advanced fibrosis with a 2 and 3 fold increase in risk, respectively. CHC patients with steatosis/NASH may merit CHC treatment sooner and closer liver monitoring post‐CHC treatment due to risks of advancing fibrosis from steatosis/NASH.

Disclosures:

Hector E. Nazario ‐ Speaking and Teaching: Merck, Gilead, Abbvie, Janssen The following people have nothing to disclose: Alex Myint, Priyanka Ancharya

Internal Medicine, Wake Forest Baptist Health, Winston Salem, NC

BACKGROUND: The U.S. Preventive Services Task Force (USPSTF) recommended in June 2013 that all patients born between 1945 and 1965 receive one‐time screening for hep

atitis C. Data evaluating the implementation of birth cohort HCV screening in clinical practice is scarce and interventions to improve it are not yet common practice. We sought to implement an electronic health record (EHR) clinical decision support (CDS) tool for HCV birth cohort screening in the clinic sites at our medical center, and to evaluate its effect. METHODS: The study was conducted at 2 general internal medicine clinics affiliated with Wake Forest Baptist Medical Center. They serve primarily underrepresented minorities (∼46% AA, ∼15% His‐ panic/Other, ∼39% White) with a large uninsured or Medicaid population The Department of Medicine Informatics Team designed a clinical decision support tool to identify individuals in the birth cohort (1945‐1965) without previous anti‐HCV antibody (Ab) in the EHR who were established with a PCP. The CDS consists of a HCV screening reminder and user design for automatic provider ordering for anti‐HCV Ab. Data on anti‐HCV Ab and HCV RNA tests in the eligible population were recorded from EHR implementation date (10/1/2012). Data was analyzed at three different time points: 12/31/14 (end of historical period), 7/1/15 (EHR CDS implementation) and 12/31/15 (CDS period). RESULTS: The population eligible for birth‐cohort screening increased over the three periods as did the proportion of patients tested for anti‐HCV Ab: 854/4,355 (20%) historical, 1220/4,994 (24%) by July 2015, and 1,700/5,578 (30%) by December 2015. There was a statistically significant decline in the proportion tested patients with a positive anti‐HCV Ab result: 59/480 (12%) in CDS period compared to prior, 218/1220 (18%); p=0.005. HCV RNA confirmatory testing tended to increase after CDS implementation (79% compared to 73% prior) The CDS tool was used to order the anti‐HCV Ab in 166/480 (35%) of the patients screened in the CDS period CONCLUSIONS: Within a short period of time and despite partial use, 6 months after CDS implementation there was a modest increase in HCV birth cohort screening. In addition, negative anti‐HCV Ab results increased during the CDS period Given the high prevalence of anti‐HCV positivity in our population we believe continued use of the CDS, with added education reinforcement, will help uncover HCV infections that otherwise may have remained undiagnosed.

Disclosures:

The following people have nothing to disclose: David N. Fitch, Ajay Dharod, Claudia Campos, Marina Nunez

¹PharmacoEpidemiology, Merck & Co. Inc, North WAles, PA; ²Gillings School of Global Public Health, University of North Carolina at Chapel Hill, CHAPEL HU, NC; Merck & Co., Inc, North Wales, PA

OBJECTIVE: Chronic hepatitis C virus (HCV) infection has been associated with the incidence of various cancers but few studies were done in the U.S. large healthcare setting. We aim to assess the incidence of common cancer sites among chronic HCV versus non‐HCV and Surveillance, Epidemiology, and End Results (SEER) general population. METHODS: We conducted a cohort study on 18+ year old Humana commercial insurance and Medicare advantage beneficiaries 2007‐2015. Chronic hepatitis C virus (HCV) patients were identified by medical claims of at least 2 ICD‐9‐CM diagnoses within 6 months Patients were required to have a 12‐month baseline of continuous insurance prior to the first HCV diagnosis. Patients with prevalent HCV or cancer diagnoses during this period were excluded. All patients have healthcare utilization during base‐

line to reduce detection bias. We identified cancer outcomes of interest with a validated algorithm: 2+ ICD‐9‐CM diagnoses within 6 months. Incident rates in the HCV cohort were estimated by standardizing for age and sex against 2000 U.S. census population and compared with rates in the non‐HCV cohort and SEER 18 areas 2007‐2013, also standardized against the same population. Non‐HCV cohort includes patients with no HCV diagnoses by the start of follow up, which is one of the healthcare utilization dates. RESULTS: HCV patients are younger (mean age 60) compared to non‐HCV patients (mean age 65) and crude incident rates are mostly similar to non‐ HCV rates. After standardizing for age and sex, incident rates increased substantially and the standardized rates are significantly higher for HCV vs. non‐HCV with rate ratios, RR (95% confidence intervals) of 1.81 (1.22, 2.69) for lung, 27.20 (17.80, 41.55) for liver, and 1.71 (0.92, 3.18) for pancreatic cancers. Rates are similar in both cohorts for other cancers with RR (95% CI) of 1.18 (0.72, 1.94) for colorectal cancer, 1.02 (0.49, 2.12) for non‐Hodgkin's lymphoma (NHL), 0.85 (0.48, 1.15) for breast, 0.73 (0.46, 1.15) for prostate, 0.79 (0.36, 1.76) for leukemia, 0.72 (0.40, 1.29) for bladder and 1.11 (0.59, 2.07) for renal. There is lower incidence of thyroid cancer for HCV vs. non‐HCV with RR 0.35 (0.14, 0.90). Analyses of SEER rates are also consistent: HCV patients having higher rates of colorectal, lung, liver, renal, pancreatic cancers and NHL vs. SEER general population. CONCLUSION: Chronic HCV is associated with higher incidence of common cancer sites versus non‐HCV or SEER general population, adjusted for age and sex. Confounding by comorbidities, social or behavioral risk factors cannot be excluded.

Disclosures:

Jean Marie Arduino ‐ Employment: Merck & Co., Inc; Stock Shareholder: merck & co, inc

Jinghua He ‐ Employment: Merck & Co. Inc

The following people have nothing to disclose: Phyo T. Htoo

¹Gastroenterology and Hepatology, AZ St Jan Brugge Oostende, Brugge, Belgium; ²Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium; ³Laboratory Medicine, Clinical Microbiology, AAZ Sint Jan Brugge Oostende, Brugge, Belgium; ⁴Gastroenterology and Hepatology, Ghent University and Hospital, Ghent, Belgium; ⁵Clinical Chemistry, Microbiology and Immunology, Ghent University and Hospital, Ghent, Belgium

Introduction and aims: The accuracy of the Versant HCV Genotype 2.0 Line Probe Assay (LiPA) to identify the subtype diversity within genotype 2 has been reported to be suboptimal. The aim of the present study was to characterize the HCV subtype diversity of patient samples previously labeled as HCV genotype 2 with the Versant HCV Genotype 2.0 LiPA. Methods: 89 consecutive HCV‐RNA samples stored in the UZ Gent HCV‐ RNA bank with genotype 2 status as determined with the Versant HCV Genotype 2.0 Assay (LiPA) were re‐genotyped with the HCV NS5B sequencing reference method (Murphy et al., 2007). Concordance for genotype group and subtype between both typing methods was calculated. The results of genotypes and subtypes obtained by NS5B sequencing were considered the reference genotypes. Results: The HCV polymerase region (NS5B) was successfully sequenced in 86/89 (97%) genotype 2 samples. The two genotyping methods resulted in concordant genotype and subtype in 10/86 samples (12 %). 55/86 (64%) samples were incompletely genotyped with LiPA (exact genotype result with an unidentified subtype or with an absence of discrimination between two subtypes). Both methods failed to assign a subtype in 8/86 (9 %) samples. 13/86 (15%) samples were misclassified with LiPA (wrong genotype or correct genotype associated with a wrong subtype) The circulating HCV recombinant form RF1_2k/1b was detected with the HCV NS5B sequencing reference method in 11 of these samples (11/86 (13%)). 9/11 (82%) of these had been labeled as “2a or 2c” with the LiPA 2.0 method. Conclusions: Direct sequencing of the HCV NS5B polymerase region revealed the presence of the recombinant form RF1_2k/1b in 13% of samples, the majority of which had been labeled as genotype “2a or c” with Versant HCV Genotype ‐LiPA 2. O. The impact on choice of optimal antiviral treatment regimen and patient care of these findings needs to be evaluated further.

Disclosures:

The following people have nothing to disclose: Hans Orlent, Wim Schuermans, Elizaveta Padalko, Isabelle Desombere, Patrick Descheemaeker, Hans Van Vlierberghe, Marijke Reynders

¹Schiff Center for Liver Diseases, Syllvester Comprehensive Cancer Center, Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL; ²Schiff Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL; ³Department of Hepatology, Yokohama City University, Yokohama, Japan

Background: Cirrhosis due to HCV infection has been associated with increased risk for hepatocellular carcinoma. The aim of our study was to assess changes in liver transient elastography (TE) and fibrosis‐4 (FIB‐4) score in patients with chronic hepatitis C (CHC) who achieved sustained viral response (SVR) Methods: Our retrospective prospective study included 60 patients with CHC and a baseline liver biopsy who achieved SVR after treatment with DAA regimens and had a pretreatment TE study and at least one follow up TE measurement at 24 weeks or later post end of treatment response (EOTR) The estimated stage of liver fibrosis based on TE was categorized as F0‐F2 (≤9.4kpa), or F3 (9.5 ‐ 12.4 Kpa), or F4/cirrhotics (TE ≥12.5 kpa). Results: Median age was 62 y/o, 56% were male, and the median BMI was 26.8 kg/m2 The median baseline TE for the entire cohort was 11.9 Kpa (range 3.8 to 65.2) and at follow up, TE decreased to 7.35 Kpa (range 2.9 to 34.8) with a median change in TE of −3.4 Kpa (range −35.3 to + 1, p=7.355e‐11).At baseline, 45% of the entire cohort were cirrhotic (78% Childs‐Pugh A) with median TE of 16.3 Kpa and FIB4 of 4.85. Follow up median TE done in the cirrhotic population after median time of 39 weeks post EOTR decreased to 11.7 Kpa and FIB4 was 2.3. The median change of TE in cirrhotic patients was −6.5 kpa (range ‐35.3 to +1, p=1.043e‐7) and for FIB4 was −1.97 (range −17.47 to −0.33, p=1.49e‐8). Non‐cirrhotic patients (TE≤12.4) comprised 55% of the entire cohort and their median change of TE was −2.4 Kpa (range −6.4 to 0.7, p=1.539e‐6) and FIB4 was −0.68 (range −2.8 to 0.41, p=2.987e‐6). 48% of the entire cohort down‐staged their liver fibrosis as determined by TE In the cirrhotic group, 59% of the patients had a drop in their stage of liver fibrosis {F4 to F0‐2 (11/27 patients), F4 to F3 (5/27 patients)} and there was no correlation in Childs‐Pugh Score and failure to achieve improvement in fibrosis stage. 82% of patients that were baseline F3 had a drop in their stage of liver fibrosis {F3 to F0‐2 (13/16 patients)}. In a multiple logistic regression analysis for factors associated with down‐staging in liver fibrosis, we found that patients who were treatment naïve were more likely to improve their fibrosis stage (OR 5.73, p=0.033). Conclusion: Liver fibrosis stage, as determined by TE, improved after achieving SVR with DAA treatments in most patients. The significant drop in TE measurement post SVR was also correlated with a significant drop in FIB4. Although cirrhotic patients had a more significant drop in their median TE when compared to non‐cirrhotic patients, they had a lower probability of improving their fibrosis stage.

Disclosures:

Eugene R. Schiff ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, Janssen, Salix Pharmaceutical, Pfizer, Arrowhead, Astrazeneca, CVS; Consulting: Acorda; Grant/Research Support: Bristol Myers Squibb, ABB‐ VIE, Gilead, Merck, Conatus, Medmira, Roche Molecular, Janssen, Orasure Technologies, Discovery Life Sciences, Siemens, Beckman Coulter, Siemens, Ortho JNH, Intercept, Beckman

The following people have nothing to disclose: Ahmad S Alawad, Masato Yoneda, Tiffannia Grant, Emmanuel Thomas

¹Med‐ Star Health Research Institute, Washington, DC; ²MedStar Health, Columbia, MD

Hepatitis C (HCV) is the most common blood‐borne infection in the US. The Birth Cohort (BC) (b. 1945‐1965) accounts for 75% of all US chronic infection. It is estimated that at least 50% of those with HCV are unaware of their condition Improved identification, testing and linkage to care protocols within large health care systems is paramount Thus, an automated MedStar‐wide Electronic Health Record EHR‐based testing protocol for identifying BC HCV infection was implemented METHODOLOGY: In January 2015, a MedStar‐wide HepC Linkage to Care Navigation program was established with Gilead FOCUS funding An automated MedStar‐wide HCV BC EHR‐based testing protocol in Primary Care Clinics was created and went live in Centricity on July 1, 2015. It has six discrete clinical decision support options Providers enter a separate screen and opt‐in for an HCV Ab with reflex test A biostatistician extracted HCV testing data via SQL, compiled it in SAS and then exported it to Excel for analysis A descriptive analysis follows. RESULTS: Between July 1, 2015 and May 1, 2016, testing occurred at approximately 76 primary provider locations and 350 providers Overall, 10% (n=6,462) of the 67,997 BC patients with a visit during the period were tested, with 3.1% (n=202) testing HCV Ab positive (HCV Ab+). Mean age of all patients was 59 ± 5.7 years; 58% (n=3,720) were women, 38% (n=2,440) had public insurance, and 45% (n=2702) were black (b/AA) More men than women (62% (n=125)) were HCV Ab+ (OR 2.3 [CI₉₅ 1.7‐3.0]). B/ AAs accounted for 55% (n=112) of those HCV Ab+ (7.5% of all b/AA men, 2.3% of all b/AA women), and were more likely to be HCV Ab+ than any other race or ethnicity (OR [CI₉₅ 1.2‐3.2]). Overall, 90.6% (183/202) of those HCV Ab+ were RNA tested, 32% (n=58/183) were found to be HCV RNA positive, or 1% of overall HCV tests (n=58/6,462) CONCLUSION: The BC testing rate for MedStar Health was less than expected at 10%, though the HCV Ab+ rate of 3.1% is similar to the 3.25% CDC BC estimate. This is perhaps due to low protocol adherence, testing those with possible lower infection risk, and regional testing differences between urban and non‐urban sites. Interestingly, though overall positivity is below the 7.4% previously reported at MedStar Washington Hospital Center, the current rate alone remained high at 6%. Work is underway to increase testing education and implement geocoding analysis to understand variability in the testing and positive rates This protocol has the potential to provide essential intelligence on the magnitude and distribution of HCV within different regions of Washington DC and Maryland and significantly impact the push to eliminate HCV.

Disclosures:

Dawn A. Fishbein ‐ Advisory Committees or Review Panels: BMS, Gilead; Grant/ Research Support: Gilead; Stock Shareholder: Gilead, Abbvie

The following people have nothing to disclose: Alexander Geboy, Whitney L. Nichols, Idene E. Perez, Stephen J. Fernandez, Peter Basch

¹Liver Disease Center, Sheba Medical Center, Ramat Gan, Israel; ²Deparmtent of Radiology, Sheba Medical Center, Ramat Gan, Israel, Ramat gan, Israel; ³Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Background: Interferon‐induced SVR in patient with HCV has been associated with a reduced rate of liver‐related morbidity and mortality. Non‐invasive methods for the assessment of liver fibrosis stage are frequently being used. We propose that cure of HCV following DAAs therapy (defined as SVR of at least 12 weeks) can lead to regression of liver fibrosis (using non‐invasive measures). Prospective assessment of the development of cirrhosis related complications and baseline predictors of liver fibrosis regression were determined. Methods: We conducted a retrospective/prospective study of HCV patients who achieved SVR after DAAs treatment (86 % Abbvie 3D regimen) with baseline liver fibrosis stage F1‐4. The fibrosis stage was determined using: elastography (shear wave, Aixplorer SuperSonic Imagine, France) or Fibrotest© (BioPredictive, France) as well as the APRI score, and FIB‐4 at baseline, 6, 12, and 24 months and each year up to 60 months after end of treatment. Results: A total of 130 patients were enrolled, 58 (48% female, mean age 60± 10 years, BMI 27.6±4.0, hypertension 41%, DM 17%, Dyslipidemia 12%) are currently eligible for analysis. The median follow up period was 9 months (IQR 7‐10). Of the 33 patients who had cirrhosis (F4) at baseline, 14 (52.4%) demonstrated improvement (defined as a change in fibrosis stage >1). Of the 17 patients with F3, 12 (70.6%) demonstrated improvement. NO changes in fibrosis score F1‐2 ?? The median (IQR) elastography score decreased significantly from 10.88 (9.4‐16.4) Kpa to 9.7 (6.7‐13.0) Kpa (p>0.0001). Baseline spleen enlargement (p> 0.001), BMI (p=0.035), bilirubin level (p=0.012), and hypertension (p=0.05) were negatively associated with improvement in fibrosis stage In multivariate analysis enlarged spleen was the only predictor of fibrosis stages no regression Baseline age, sex, genotype, history of previous antiviral treatment, other comorbidities (DM, Dyslipidemia), ALT, AST, platelets, INR, albumin, creatinine, esophageal varices, APRI, and FIB4 were not predictors of fibrosis regression. Conclusions: The majority of our subjects

(44.8%) demonstrated improvement in liver fibrosis stage by non‐invasive methods. Some of the clinical parameters were negative predictors of liver fibrosis regression. Longer follow up period is required to determine the impact of the DAAs treatment in HCV patients.

Disclosures:

The following people have nothing to disclose: Yana Davidov, Yeroham Kleinbaum, Oranit Cohen‐Ezra, Ella Veitsman, Tania Berdichevski, Peretz Weiss, Sima Katsherginsky, Hasid Avishag, Keren Tsaraf, Ziv Ben Ari

Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY

Background: Hepatitis C (HCV) treatment guidelines recommend prioritizing patients with advanced fibrosis. However, strict insurance requirements of abstinence from illicit drug use may limit access to treatment. Objective: We aim to identify socioeconomic barriers to treatment initiation in HCV patients with advanced fibrosis. Methods: 1,048 new patients were evaluated for HCV treatment at the University of Kentucky Liver Clinic from July 1,2014 to June 30, 2015. 103 patients (10%) had a FibroSure™ suggesting stage 3‐4 fibrosis were included in the cohort for analysis Patients who had cirrhosis were compensated. Demographic, clinical and socio‐economic data, such as insurance, proximity of residence to the clinic, drug and alcohol use, history of incarceration were collected and compared between patients who were treated versus those not treated or had delayed treatment (i e treated started beyond 6months after initial visit). Multivariate logistic regression was done to evaluate factors predicting treatment delay and non‐initiation. Results: The mean interval between initial consult to treatment start was 165 days (5 months). Among the 103, 49 (48%) were treated with direct‐acting antivirals (DAAs) within 6 months, and 54 (52%) had delayed (mean of 10 months) initiation of treatment (n=20) or did not receive treatment (n=34). The mean age was 53 (± 9). Seventy five percent were male, 58% were estimated to live within 60 miles from the clinic, 57% had a history of incarceration, 80% a remote history of illicit drug use, and 45% a remote history of alcohol abuse Between the treated and delayed/not‐treated groups, there were no significant differences in these factors The two groups, however, differ in insurance type, with the treated group more likely to have a non‐Medicaid insurance than the delayed/not‐ treated group (67% vs. 32%, p<0.001). The patients who had delayed or no treatment had higher rates of recent history of illicit drug use (68% vs 32%, p<0.03) and positive urine drug screen on evaluation (63% vs 38%, p<0.03). On multivariate analysis, the insurance type was the only significant predictor of treatment initiation, with patients on non‐Medicaid insurance having 4× higher likelihood to start treatment within 6 months vs. those on Medicaid (OR 3.9, 95% CI 1.6‐9.5, p<0.005). Conclusion: Despite the emergence of highly effective HCV DAAs, there remains barriers to treatment initiation in patients with advanced fibrosis Patients with non‐Medicaid insurance are more likely to receive prompt treatment compared to those with Medicaid.

Disclosures:

The following people have nothing to disclose: Patricia Santos, Ronald Racho, Moaz Abdelwadoud, Megan Cooper, Candice B Kuns‐Adkins, Jens Rosenau, Anna Christina Dela Cruz

Internal Medicine, Yale‐Waterbury Hospital, Waterbury, CT

Background:In 2012 the CDC published guidelines supporting one‐time screening for hepatitis C (HCV) in all persons born between 1945‐65. It is estimated that 75% of adults infected with HCV fall within this cohort Furthermore, it is projected that this preventative health intervention would lead to the diagnosis of 800,000 unknown cases and the prevention of 120,000 deaths. Aim:The primary objectives were to measure adherence to HCV screening in a continuity practice staffed by internal medicine residents and to measure the effect of interventions to enhance HCV screening. Methods:We performed a retrospective chart review of a random sample of patients born between 1945‐1965. In order to meet inclusion criteria, the patients must have had an HCV status that was unknown and must have been seen by a primary care provider ≥ 2 times between January 1 and December 31, 2013. After initial data was extracted, providers were given reminders for HCV screening guidelines through emails, lectures and conferences Chart review of patients was done to measure improvement in HCV screening rate after the intervention Data was analyzed using chi‐squared testing. Results:Out of 294 patients reviewed before intervention, 200 met inclusion criteria Only 17 (8.5%) patients were offered screening for HCV After intervention, 100 patients met the inclusion criteria. 34 patients were screened for HCV Screening rate increased by 325 percent after the intervention. Conclusion: Adherence to HCV screening guidelines in a resident continuity practice prior to any educational intervention was low at 8.5 percent Regular reminders through emails, conferences and lectures can increase the awareness and improve screening rate In our resident continuity practice, HCV screening rate improved by 325% by increasing awareness of the HCV screening guidelines through regular reminders and education of house staff.

HCV screening rate, before and after intervention

Disclosures:

The following people have nothing to disclose: Ali Aamar, Kamraan Madhani, Prabhdeep Singh, David Chia

¹Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY; ²Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; ³Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, MN; ⁴Department of Medicine, Division of Rheumatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

Background/Objectives: Hepatitis C virus (HCV) infection is one of the leading causes of cirrhosis. As a result of chronic inflammatory response to the virus, HCV‐infected patients may be at a higher risk of venous thromboembolism (VTE). However, the data on this association is unclear. This systematic review and meta‐analysis was conducted with the aims to summarize all available evidence. Methods: A literature search was performed using MEDLINE and EMBASE from inception to April 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of VTE among HCV‐infected patients versus subjects without HCV infection were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random‐effect, generic inverse variance method Results: Three studies met our eligibility criteria and were included in analysis. The pooled RR of VTE in HCV‐infected patients versus subjects without HCV infection was 1.38 (95% CI, 1.08‐1.77, I² =40%). Subgroup analysis showed that risk was increased for both pulmonary embolism (PE) and deep venous thrombosis (DVT) even though without adequate power to demonstrate statistical significance (Poole RR of 1.34, 95% CI, 0.67‐2.66 for PE and pooled RR 1.45, 95% CI, 0.932.77 for DVT). Conclusions: Our study demonstrated a significantly increased risk of VTE among HCV‐infected patients. Further studies are required to clarify how this risk should be addressed in clinical practice

Forest plot of the included studies hepatitis C infection and risk of venous thromboembolism (Top), pulmonary embolism (Middle), and deep venous thrombosis (Bottom)

Disclosures:

The following people have nothing to disclose: Karn Wijarnpreecha, Charat Thongprayoon, Panadeekarn Panjawatanan, Patompong Ungprasert

¹Ipsos Healthcare, New York, NY

Background and Aims: Over the last two years, The European Medicines Agency has approved highly effective Direct Acting Antiviral (DAA) regimens for the treatment of Hepatitis C. Access to the revolutionary DAAs, sofosbuvir (and/or ledipasvir), daclatasvir, or ombitasvir/paritaprevir/ ritonavir with/ without dasabuvir is not pervasive; there remains country level differences due in some part to variations in national level insurance and country‐manufacturer dealings Apart from these variables, patient level factors also influence access The aim of this study was to analyze and order the influence of residency, demographics and clinical conditions on access to DAAs using recent patient chart audit data and Chi‐squared Automatic Interaction Detection (CHAID). Method: Ipsos' HCV Therapy Monitor, running since 2006 in the EU, reports on ∼240 physicians per quarter across Italy, Spain, France, United Kingdom, and Germany. Physicians provide patient demographic, disease and treatment data on HCV patients seen within each period. The EU Therapy Monitor Q2‐Q4 2015 data and a CHAID analysis were used to create a decision tree. The tree determines the hierarchy of influence that viral load, comorbidities, country, substance abuse, and fibrosis score has on patient access to DAAs Results: The CHAID analysis split the data by fibrosis level, revealing that fibrosis had the strongest impact on DAA access Country and substance abuse status were, in most cases, the next most influential variables on treatment access When focusing on F2 patients in Germany and Spain, those not abusing substances had a ∼80% and ∼60% chance of DAA access, whilst F2 abusers in Germany and Spain had a lower chance at ∼50% and 5%, respectively. A similar trend persisted throughout the individual fibrosis level cohorts apart from cirrhotic patients, where clinical characteristics had a greater influence than residency Conclusion: The decision tree revealed that treatment access is significantly dependent on fibrosis, country and substance abuse, with viral load and comorbidities playing a lesser role All EU5 countries have similar fibrosis level adjudication, but then experience minor divergence in how substance abuse status is integrated in access decisions The difference in treatment rates between abusers and non‐abusers diminishes from F0‐F4 Abusers are commonly denied because of the non‐compliance risk, yet denying access now leaves the potential for future strain on payer systems.

Disclosures:

The following people have nothing to disclose: Jason Katz, Sarah Brown, Mohammed Aiyaz, Elizabeth Baynton, Sabina Heinz

¹Virology & INSERM Unit U955, Henri Mondor University Hospital, Creteil, France; ²Hepatology, Henri Mondor, Creteil, France

Background: Sensitive and accurate hepatitis C virus (HCV) RNA detection and quantification is essential for the management of chronic hepatitis C therapy. Currently available platforms and assays are usually batched and require at least one full day of work to complete the analyses. Objective: The aim of this study was to evaluate the ability of the newly developed Aptima HCV Quant Dx assay (Hologic Inc., San Diego, CA), a transcription‐mediated amplification (TMA)‐based assay making use of the fully automated Panther system, that eliminates the need for batch processing and automates all aspects of nucleic acid testing in a single step, to accurately detect and quantify HCV RNA in a large series of patients infected with different HCV genotypes. Results: The limit of detection was estimated to be 2.3 IU/mL. The specificity of the assay was 98.6% (95% confidence interval: 96.1%‐99.5%). Intra‐assay and inter‐assay coefficients of variation ranged from 0.09% to 5.61%, and 1.05% to 3.65%, respectively. The study of serum specimens from patients infected with HCV genotypes 1 to 6 showed a satisfactory relationship between HCV RNA levels measured by the Aptima HCV Quant Dx assay, and both realtime PCR comparators [Abbott RealTime HCV (Abbott Molecular, Des Plaines, IL) and Cobas AmpliPrep/Cobas TaqMan HCV Test, version 2.0 (CAP/CTM HCV v2.0, Roche Molecular Systems, Pleasanton, CA), assays]. Conclusion: The new Aptima HCV Quant Dx assay is sensitive, reasonably specific and reproducible and accurately quantifies HCV RNA in serum samples from patients with chronic HCV infection, including patients on antiviral treatment Quantification is linear over the full dynamic range of quantification, which covers values observed in both untreated and treated patients with chronic HCV infection The Aptima HCV Quant Dx assay can thus be confidently used to detect and quantify HCV RNA in both clinical trials with new anti‐HCV drugs and clinical practice in Europe and the US.

Disclosures:

Stephane Chevaliez ‐ Advisory Committees or Review Panels: Janssen; Speaking and Teaching: Gilead, BMS, Abbvie

Christophe Hezode ‐ Speaking and Teaching: Roche, BMS, MSD, Janssen, abb‐ vie, Gilead

Jean‐Michel Pawlotsky ‐ Advisory Committees or Review Panels: Abbvie, Bristol‐Myers Squibb, Gilead, Janssen, Merck; Grant/Research Support: Gilead; Speaking and Teaching: Bristol‐Myers Squibb, Gilead, Merck, Janssen, Gilead

The following people have nothing to disclose: Fabienne Dubernet, Claude Dauvillier

¹Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; ²Internal Medicine, National Taiwan University Hospital, Yun‐Lin Branch, Douliou, Taiwan

Background: Little is known about the risk of hepatitis B virus (HBV) reactivation in hepatitis C virus (HCV)‐infected patients receiving interferon (IFN)‐free direct acting antiviral agents (DAAs) Methods: HCV‐infected patients receiving 12 weeks of IFN‐free DAA therapies were consecutively enrolled The baseline, on‐treatment, and off‐therapy HBV DNA, HBV surface antigen (HBsAg), HBV surface antibody (anti‐HBs), and alanine aminotransferase (ALT) were serially examined HBV reactivation was defined as detectable serum HBV DNA following baseline undetectable HBV DNA, or an increase of ≥ 1 log₁₀ IU/mL HBV DNA compared to baseline detectable HBV DNA. Significant HBV‐related ALT flare was defined as ALT ≥ 5 times upper limit of normal (ULN) or ALT ≥ 2 times of the baseline level with concomitant HBV DNA > 2,000 IU/mL. HBV‐related hepatic decompensation was defined as significant HBV‐related ALT flare combined with jaundice, coagulopathy, hepatic encephalopathy or ascites. Results: Of the 103 patients enrolled, 3 (2.9%) had HBV reactivation, but none of them had significant HBV‐related ALT flare or hepatic decompensation. Of 6 HBsAg‐positive patients, 3 (50%) had HBV reactivation. In the remaining 97 HBsAg‐negative patients, none had HBV reactivation after DAA therapy. In patients with baseline HBsAg negativity with/without anti‐HBs positivity, there were no changes of HBV serological markers. Conclusions: The risk of HBV reactivation was low in HCV‐infected patients receiving IFN‐free DAA treatment, and HBV reactivation was limited to HBV/HCV‐coinfected patients. Furthermore, the risk of HBV‐related ALT flares or hepatic decompensation is also minimal in those with HBV reactivation.

Disclosures:

Pei‐Jer Chen ‐ Advisory Committees or Review Panels: BMS, GSK, BMS, GSK, Medigene; Consulting: Medigen, Pharmaessentia; Grant/Research Support: Vazgenetics; Independent Contractor: J & J; Speaking and Teaching: Roche, Roche

The following people have nothing to disclose: Chen‐Hua Liu, Chun‐Jen Liu, Tung‐ Hung Su, Yu‐Jen Fang, Hung‐Chih Yang, Ding‐Shinn Chen, Jia‐Horng Kao

¹Infeccious disease, Consorcio Hospital General Universitario, Valencia, Spain; ²Infectous Disease, 2 Hospital Universitario Donostiarra‐OSI Donostialdea, San Sebastian, Spain; ³3 Unidad Mixta Infección y Salud Publica FIS‐ ABIO‐Universitat de Valencia, Valencia, Spain: ⁴Infectious Disease, Hospital Universitario central de Asturias, Oviedo, Spain; ⁵Internal Medicine, Hospital Universitario Virgen de Valme, Sevilla, Spain; ⁶Internal Medicine, Hospital Universitario Dr. Negrin, Las Palmas, Spain: ⁷HIV Unit, Hospital Universitario La Paz Madrid, IdiPaz, Madrid, Spain; ⁸Infectious Disease, Hospital General Universitario Alicante, Alicante, Spain; ⁹Internal Medicine, Complejo Hospitalario de Cdceres, Caceres, Spain: ¹⁰IMIBIC, Hospital Universitario Reina Sofia, Universidad de Córdoba, Cordoba, Spain; ¹¹Infectious Disease, Hospital Universitario Marqués de Valdecilla, Universidad de Cantabria, Santander, Spain; ¹²Infectious Disease, Hospital Gregorio Marañón, Madrid, Madrid, Spain; ¹³Infectious Disease, Hospital Germans Trias i Pujol, Badalona, BAdalona, Spain; ¹⁴Infectious Disease, Hospital Virgen del Rosell, Cartagena, Cartagena, Spain; ¹⁵Infectious Disease, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Tenerife, Spain; ¹⁶Internal Medicine, Hospital de La Rioja y Complejo Hospitalario San Millán‐ San Pedro‐de La Rioja, Logroño, Spain; ¹⁷Internal Medicine, 17 Complejo Hospitalario Universitario de Albacete, Albacete, Spain; ¹⁸Microbiologia, Hospital Clínico Universitario de Santiago de Compostela, Santiago De Compostela, Spain; ¹⁹Infectious Disease, Hospital Universitario Álvaro Cunqueiro, Vigo, Vigo, Spain; ²⁰Infectious Disease, Hospital Universitari Vall d'Hebron, Barcelona;, Barcelona, Spain; ²¹Internal Medicine, Hospital Can Misses, Ibiza, Ibiza, Spain; ²²Infectious Disease, Hospital Miguel Servet, Zaragoza., Zaragoza, Spain; ²³Infectious Disease, Hospital Genral Universitario Valencia, Valencia, Spain

Introduction Information about the epidemiology and the impact of HCV genotype 4 (G4) in HCV/HIV patients in Spain is scarce. There is no data available on the number and spread of HCV G4 lineages. Design and Setting In order to determine the prevalence and distribution pattern of HCV G4 in HCV/HIV co‐infected individuals, a multicenter, retrospective, observational cohort study was conducted in 21 Spanish hospitals. A descriptive epidemiological analysis on a random sample of cases was performed. A portion of the HCV NS5B region (796 nucleotides) was amplified and sequenced in 207 associated plasma samples. HCV subtyping was performed by using the COMET HCV online tool and compared with our subtyping system based on phylogenetic reconstruction A maximum‐likelihood phylogenetic tree with bootstrap support for branches built with RAxML was used for detection of clusters of sequences. Results Within the initial cohort of 24,539 HIV‐infected patients, 6,047 individuals were HIV/ HCV co‐infected and 1,148 of them presented VHC G4 (20%). Characteristics: Average age 50, male (75%), injection drug user with more than 20 years of estimated time of infection and stage of hepatic fibrosis greater than or equal to F2 (55%). In most regions the prevalence of HCV G4 exceeded that of G3 Within HCV G4, average prevalences of subtypes 4d and 4a were 79% and 21%, respectively. A south‐north distribution pattern of HCV G4 subtypes was detected The proportion of patients with HCV 4d is mainly present in the north of Spain while subtype G4a tends to increase from the north to south with a presence greater than or equal or G4d in southern Spain In addition, we have detected a significant cluster of subtype 4d formed by 8 sequences from Madrid and one from Canary Islands that share a recent common ancestor Moreover, these 9 genetically close sequences along with 20 sequences belonging to Dutch HCV/HIV co‐infected individuals from a study published in 2009, also formed a significant cluster This clustering suggests that transnational transmission networks of HCV associated with risk factors can be detected by using this methodology In contrast, no significant clusters were found among subtype 4a sequences Conclusions There is a high percentage of HCV/HIV co‐infection (24.64%) in Spanish patients with a high prevalence of HCV G4 (20%). The predominant subtype is 4d (71%), especially in northern Spain. Conversely, subtype 4a has a presence similar or greater than subtype 4d in southern Spain and Canary Islands. Phylogenetic analysis detected a group of closely related subtype 4d sequences that suggests the existence of transmission networks of HCV/HIV associated to risk factors.

Disclosures:

Miguel A. von Wichmann ‐ Grant/Research Support: Abbott, Janssen, MSD, Bristol‐Myers Squibb, Gilead

Rafael Granados ‐ Advisory Committees or Review Panels: Abbvie; Consulting: Janssen; Speaking and Teaching: Abbive, Janssen, Gilead

The following people have nothing to disclose: Enrique Ortega Gonzalez, Maria Alma Bracho, Victor Asensi, Jose Antonio Mira, Marisa Montes, Livia Giner, Carlos Martin, Antonio Rivero‐Juárez, Francisco Arnaiz de las Revillas, Juan Berenguer, Cristina Tural, Francisco Vera, Juan Luis Gomez‐Sirvent, Jose Antonio Oteo, Elisa Martínez, Antonio Aguilera, Luis Morano, Jorge Navarro, Roberto Oropesa, Javier Moreno, Purificacion Rubio‐Cuevas

¹Institute for Digestive Health & Liver Diseases, Mercy Medical Center, Baltimore, MD; ²Medicine & Surgery, University of Maryland School of Medicine, Baltimore, MD

In inner cities, the prevalence rates of HCV are thought to be very high, but diagnosis and linkage to care has been sub‐optimal. CDC estimates those Baby Boomers, born between 1945 and 1965, account for more than 75 percent of Americans with Hepatitis C. However, screening of this population has been dismal despite the recommendations from CDC, USPSTF, and CMS. Our institution provide primary healthcare to 33,736 baby boomers via 41 primary care physicians, but only less than 10% of population at risk was screened, prior to our intervention, 2 years after CDC published the recommendations. Objectives: The objective of our study was to improve the HCV screening of baby boom generation Methods: We used a 2 pronged approach. We created a ‘pop‐up’ in EMR prompting primary care physicians to order the screening test when patients visited them We also sent letters to patients explaining the rationale for screening along with an order form for the blood test The letters were sent out only after approval by the primary care physician, and were addressed to the patient and signed by the primary care physician Patients who were found to be positive for HCV were educated and linked to care by dedicated coordinators We collected the numbers of completed orders by ‘pop‐up’ prompting and through letters using EMR To improve the disease awareness, we also conducted CME events for primary care physicians, and additionally, coordinators met with their office staff and provided education material Results: In this ongoing study, we have mailed letters to 10,189 patients of 14 primary care physicians in the first 12 months During this period, the screening rates increased by over 300% compared to previous 12 months. 1,167 patients were screened through the mailed orders, and 26 patients were found to HCV antibody; 25 of these patients have been tested for HCV RNA, and only 10 were positive for HCV RNA (0.86% of total screened). Additionally, 1,404 patients were screened through the EMR pop‐up, identifying another 18 with HCV antibody; all of these positive patients were tested for HCV RNA, and 6 were positive for HCV RNA (0.43% of total screened) Of those screened through the pop‐up, about 28% had also received a letter Conclusion: The use of automated processes incorporated into electronic medical record systems, can be an effective way of increasing screening rates for viral infections. This in combination with a targeted mailing campaign can expand the ability of primary care physicians to test their patients, and identify infected individuals The prevalence rate of HCV in baby boom generation at our institution appears to be lower than previously reported.

Disclosures:

Paul J. Thuluvath ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/Research Support: Gilead, AbbVie, BMS, Isai, Salix; Speaking and Teaching: AbbVie, Bayer/Onyx, Gilead

The following people have nothing to disclose: Harris Feldman, Asher Horowitz, George Lowe

¹Medicine, Drexel University, Philadelphia, PA; ²University of Pennsylvania, Philadelphia, PA

BACKGROUND: While adults born between 1945‐1965 constitute the largest group of people in the United States with chronic hepatitis C infection (HCV), young adults, particularly with a history of injection drug use, are increasingly diagnosed. Unfortunately, young adults are known to have low levels of engagement with the health care system where HCV testing is offered We sought to describe the characteristics of young adults receiving HCV testing through the ‘C’ a Difference program, an academic‐community partnership that provides free HCV testing in three community organizations METHODS: Participants were recruited through a convenience sample of adults presenting for HCV testing at one of three community health programs in Philadelphia, Pennsylvania, between June 2014 and December 2015. Participants completed a survey at the time of HCV testing that included questions on risk factors, primary care and prior HCV testing. Descriptive statistics were performed on survey data, with comparisons made between young adults (ages 18‐35) and older adults. RESULTS: During the study period 2131 adults, of whom 761 (36%) were young adults, presented to one of the community health programs Among the 1511 (71%) adults who consented to the study and completed the survey 534 (35%) were young adults. Compared to older adults, the young adults in our sample were less likely to have been incarcerated (47% vs 60%, p<0.001) and more likely to have a tattoo from an unregulated setting (36% vs 21%, p<0.001). Young adults were also more likely than older adults to use prescription drugs (23% vs 14%, p<0.001), while older adults were more likely to use crack (36% vs 12%, p<0.001) and cocaine (37% vs 18%, p<0.001). Despite several risk factors young adults were less likely than older adults to be insured (68% vs 77%, p=0.001) or have primary care (60% vs 69%, p<0.001). Rates of prior HCV testing were similar between the two groups, with 36% of young adults and 35% of older adults reporting prior testing (p=0.424) Among those who had been previously tested, young adults were more likely to have been tested at a location other than their PCP's office (58% vs 43%, p=0.001). Among the 303 young adults who had not been previously tested either in a PCP office or elsewhere 11 (4%) were found to be positive through ‘C’ a Difference. CONCLUSION: This study suggests that community‐based programs are an important site for engaging and testing young adults who are at risk for HCV and who may not have access to regular health care. With the epidemiology of HCV revealing a rise of cases among young adults, support is warranted to promote testing in locations frequented by this group.

Disclosures:

Michelle Dougherty ‐ Employment: Opening Doors for Diverse Populations to Health Dispairites Research Under the NIH 1R25MD006792‐01 The National Institute on Minority Health and Health Disparities (NIMHA) Dr. Shannon Marquez, PI; Grant/Research Support: Gilead Sciences

Lora Magaldi ‐ Grant/Research Support: Gilead Sciences

Carla Coleman ‐ Grant/Research Support: Gilead Sciences

Stacey Trooskin ‐ Advisory Committees or Review Panels: Gilead Sciences;

Grant/Research Support: Gilead Sciences

The following people have nothing to disclose: Jeffrey Hom, Ta‐wanda Preston

Medstar Health Research Institution, Washington, DC

Few studies have evaluated possible regression of liver fibrosis (LF) and cirrhosis (LC) after cure of chronic hepatitis C (HCV). Past limitations included the lack of efficacy of interferon‐based drugs. This study examines effects of sustained virologic response (SVR) from new Direct Acting Antivirals(DAAs) on changes in LF or LC using non‐invasive tests, fibrosis‐4 (FIB‐4) and aspartate amino transferase to platelet ratio index (APRI). Methods: A retrospective cohort study was conducted using clinical data from HCV patients from January 2014 to April 2016 at MedStar Washington Hospital Center comparing FIB‐4/APRI scores in patients during and after DAA therapy who achieved SVR and those not treated Safety labs were collected from treatment group at baseline, 4 weeks, end of treatment and 12 weeks after treatment; and from untreated patients at 4 equivalent time points. Chi‐Square and Wilcoxon Tests were used to assess correlations between covariates Multivariate logistic regression was used to assess correlations between FIB‐4 and APRI. Results: Of the 149 patients treated, mean age was 61.4 ± 6 years, 60% were male, and 89% were black. There were no statistically significant differences between treated and controls regarding sex, and race/ethnicity; age was significantly older in the treated group (p<0.009). The majority were HCV mono‐infected and previously treatment naive, though the latter had less patients treated (75.2 v 87.5% [p=0.006]). Regarding FIB‐4: At baseline, there were more LF/LC patients in the treatment group (79.1 v 62.5% [p=0.002]); FIB‐4 scores were significantly higher in controls compared to the treatment group at time 2, 3, and 4 (p=0.04, 0.007, and 0.03 respectively). Regarding APRI: At baseline, there were fewer LF/LC patients in treatment group (30.2 v 38.8% [p=0.12]) but this was not statistically significant; APRI scores were significantly higher in controls compared to the treatment group at time 2, 3, and 4 (all p <0.0001). For APRI staging of LC vs. non‐LC, the odds for developing LC at time 3 were 3.7 times higher for non‐ treated (OR_adj 3.7 [CI₉₅H 5‐9.6]). For FIB‐4 staging of LC vs. non‐LC, odds for developing LC at times 3 and 4 were 2.13 and 3.04 times higher respectively, (ORs_adj 2.1 [CI₉₅1.1‐4.2], 3.2 [CI₉₅1.4‐6.7]). APRI and FIB‐4 scores have been validated as non‐invasive markers of liver disease They have not been examined for those treated with new DAAs and achieved SVR Our study shows that FIB‐4 and APRI scores improved, even in those with advanced disease, compared to those not treated during the same period This is further evidence that achieving SVR may lead to improvement in liver disease

Disclosures:

Dawn A Fishbein ‐ Advisory Committees or Review Panels: BMS, Gilead; Grant/ Research Support: Gilead; Stock Shareholder: Gilead, Abbvie

The following people have nothing to disclose: Whitney L Nichols, Alexander Geboy, Sameer Desale, Idene E Perez

¹Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, NY; ²Bio‐chemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; ³Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ⁴Medicine, Mayo Clinic, Rochester, MN

Background/Objectives: Gallstones and its complications are one of the most common hepatobiliary tract diseases Several epidemiologic studies have suggested that patients with hepatitis C virus (HCV) infection might be at an increased risk of gallstones However, the data on this relationship remain inconclusive This meta‐analysis was conducted with the aims to summarize all available evidence Methods: A literature search was performed using MEDLINE and EMBASE database from inception to May 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of gallstones among HCV‐infected patients versus subjects without HCV infection were included Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random‐effect, generic inverse variance method Results: Eleven studies met our eligibility criteria and were included in analysis. The pooled OR of gallstones in HCV‐infected patients versus subjects without HCV infection was 1.83 (95% CI, 1.35‐2.48, I² =89%). Subgroup analysis showed that significant risk was increased for both male (Pooled OR of 2.07, 95% CI, 1.14‐3.76) and female (Pooled OR of 3.00, 95% CI, 2.16‐4.17). Conclusions: Our study demonstrated a significantly increased risk of gallstones among HCV‐infected patients. Further studies are required to clarify how this risk should be addressed in clinical picture.

Forest plot of the included studies hepatitis C infection and risk of gallstones

Disclosures:

The following people have nothing to disclose: Karn Wijarnpreecha, Charat Thongprayoon, Panadeekarn Panjawatanan, Natasorn Lekuthai, Patompong Ungprasert

¹Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan; ²Department of Virology & Liver unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

Background: The quantification of hepatitis C virus core antigen (HCV Ag) in serum is useful to estimate viral replication. A newly developed and fully automated chemiluminescence enzyme immunoassay (CLEIA) for HCV Ag will be available in Japan. The aim of this study is to compare the new HCV Ag assay with conventional ones and to evaluate its clinical utility Methods: This study protocol was approved by the appropriate institutional ethics review committees The new HCV Ag assay (Lumipulse Presto HCV Ag [LP‐Presto HCV Ag] [Fujirebio, Inc. ]) was compared with two conventional assays (Lumipulse Ortho HCV Ag [LP‐Ortho HCV Ag] [Fujirebio, Inc. ] and Architect HCV Ag [Abbott Japan]). 1) A total of 220 frozen sera (83 were positive and 137 were negative by LP Ortho HCV Ag) in our hospital, and a total of 206 fresh sera which were negative by LP‐Ortho HCV Ag obtained on the day when the examination was performed were used in this study. As basic examinations, reproducibility, stability, and quantitation limit were examined. Correlation and concordance rates between LP‐Presto HCV Ag and conventional assays were performed. Specificity test for LP‐Presto HCV Ag were examined 2) A total of 42 frozen sera with hypergammaglobulinemia which were negative by LP‐Ortho HCV Ag were measured by LP‐Presto HCV Ag Results: 1) Reproducibility, stability, and quantitation limit of LP‐Presto HCV Ag were all supportive results to efficacy In the 83 cases positive by LP‐Ortho HCV Ag, correlation was found with LP‐Ortho HCV Ag (y=1.023×+131.5, r=0.967), and with Architect HCV Ag (y=1.381×‐56.76, r=0.941). There were 1 discrepancy between Lumipulse Presto and LP‐Ortho HCV Ag, and 2 discrepancies between Lumipulse Presto and Architect HCV Ag. The concordance rates were 98.8% between Lumipulse Presto and LP‐Ortho HCV Ag, and 97.6% between Lumipulse Presto and Architect HCV Ag. In the 133 cases negative by LP‐Ortho HCV Ag, there were no discrepancies. A total of 137 frozen samples and 206 fresh samples negative by LP‐Ortho HCV Ag were negative by LP‐Presto HCV Ag under the cutoff value 20 fmol/L. Meanwhile, there was 1 discrepancy between these assays under the cutoff value 10 fmol/L. 2) Of the 42 frozen samples with hypergammaglobulinemia and negative by LP‐Ortho HCV Ag, 41 samples were negative and one sample (IgG 7,125 mg/dL) showed false‐positive by LP‐Presto HCV Ag. Conclusions: The results of basic examinations and specificity test are reliable, and the concordance rates with conventional assays are high The nonspecific reaction caused by hypergammaglobulinemia is found to be reduced The new assay “Lumipulse Presto HCV Ag” can be used with high clinical efficiency.

Disclosures:

Yasuhito Tanaka ‐ Grant/Research Support: Chugai Pharmaceutical CO., LTD., MSD, abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Bristol‐Myers Squibb

The following people have nothing to disclose: Takako Inoue, Tomoyuki Ohike, Takaaki Goto, Kumiko Ohne, Yuji Tsuzuki, Shigeru Sato

¹Faculty of Medicine and Life sciences, Hasselt University, Tongeren, Belgium; ²Faculty of Medicine and Life sciences, Hasselt University, Hasselt, Belgium; ³Centra voor Alcohol en andere Drugproblemen, Hasselt, Belgium; ⁴Department of Clinical Biology, Ziekenhuis Oost‐Limburg, Genk, Belgium; ⁵Department of Gastro‐Enterology and Hepatology, University Hospitals KULeuven, Leuven, Belgium; ⁶Department of Gastro‐Enterology and Hepatology, Ziekenhuis Oost‐Limburg, Genk, Belgium

Introduction Hepatitis C viral infection (HCV) has become a curable disease due to the development of direct acting antivirals (DAA). Therefore, the World Health Organization (WHO) has set a target to eliminate HCV The largest group at risk for HCV at present are people who inject drugs (PWID), especially in the western world Due to various barriers, this risk group is still underserved for HCV Our goal was to study if a case management policy could improve uptake for screening and treatment for HCV in PWID Methods We performed a prospective, interventional cohort study, evaluating the effect of case management on screening and treatment for HCV in PWID in an opiate substitution treatment (OST) setting in Limburg (Belgium) The goal was to address the PWID at this setting and to provide all the steps of the continuum of care, proposed by Meyer JP et al. (Int J Drug Policy, 2015). The cohort existed of four groups of PWID: firstly, a large group who received methadone at their local pharmacy A second large group received methadone at the OST setting Thirdly a smaller a group who were active users in a needle exchange program And finally a small group who were recruited after referral to the hospital (former PWID) Results The results are presented in Figure 1 In all of the groups more than 80% of the cases were screened, except in the pharmacy group: these presented only a few times a year in the OST setting which could explain the lower screening rate However, when addressed, more than 85% of the PWID in the pharmacy group were tested In our PWID cohort, approximately 29% was HCV RNA positive From these chronically infected PWID, 62% were assessed for treatment 95% of them were eligible for antiviral treatment However, treatment could only be started within the Belgian reimbursement criteria (requirement of F3 or F4 Metavir fibrosis score) As such, 51% were ruled out for therapy at present and treatment was started in 43% Conclusion Case management is an effective way to screen a well‐defined cohort of high‐risk individuals for HCV and also improves treatment uptake.

Disclosures:

Frederik Nevens ‐ Consulting: MSD, CAF, Intercept, Gore, BMS, Abbvie, Novartis, Durect, Janssens‐Cilag, Ono Pharma, Promethera Biosciences; Grant/ Research Support: Ferring, Roche, Astellas, Novartis, Janssen‐Cilag, Abbvie

Geert Robaeys ‐ Advisory Committees or Review Panels: MSD, Janssens, Gilead, Abbvie, BMS

The following people have nothing to disclose: Rob Bielen, Rita Verrando, Joris Penders, Els Oris

¹Institute for Technology Assessment, Massachusetts General Hospital, Harvard Medical School, Boston, MA; ²Swedish Medical Center, Seattle, WA; ³Henry Ford Hospital, Detroit, MI; ⁴Georgia Institute of Technology, Atlanta, GA; ⁵Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX; ⁶Baylor College of Medicine, Houston, TX; ⁷University of Pittsburgh, Pittsburgh, PA

Purpose: The introduction of oral direct‐acting antivirals (DAAs) has dramatically changed the landscape of HCV treatment. Many more patients are eligible for therapy due to the absence of interferon and ribavirin, and real‐world effectiveness mirrors the results of Phase 3 clinical trials. Our objective was to quantify the number of HCV (GT 1‐6) patient population who fail on currently approved oral DAAs (including NS5A vs. non‐NS5A failures) over time in the U.S. Methods: We used our Hepatitis C Disease Burden Simulation model (HEP‐SIM), which was previously validated with NHANES and CDC studies and used to project changes in HCV prevalence in the U.S. We simulated the current clinical management of HCV including the birth‐cohort and risk‐based screening Using market research data from IMS and IPSOS, we modeled DAA treatment in different waves starting with the launch of 1^st‐generation DAAs in 2011, followed by 2^nd‐generation DAAs including sofosbuvir, simeprevir and ledipasvir in 2014, and multiple NS5A‐inhibitor containing DAAs in 2015. SVR rates were obtained from real‐world TRIO and TARGET datasets Within our model, patients who failed an NS5A were not eligible for NS5A re‐treatment until 2018, unless they were cirrhotic. We projected the number of patients undergoing treatment between 2014 and 2020; and the number of patients who failed DAAs (NS5A and non‐NS5A). Results: We estimated that 1.41 million patients would receive treatment with 2^nd‐generation DAAs from 2014 to 2020. Of these, 117,000 would fail to achieve SVR with DAAs, of which 58% are NS5A inhibitors failures (Figure 1) The characteristics of patients who fail on DAAs were: 51% cirrhosis, 72% GT1, 14% GT2, 9% GT3, and 5% GT4‐6. Conclusions: Even in the era of highly efficacious DAAs, a significant number of patients will fail to achieve SVR and will have limited re‐treatment options This population represents a group with significant unmet medical need. Safe and effective therapies are needed for this population to prevent the longterm sequelae of HCV.

Disclosures:

Jagpreet Chhatwal ‐ Consulting: Merck & Co., Inc., Gilead, Complete HEOR Solutions; Grant/Research Support: NIH/National Center for Advancing Translational Sciences

Kris V. Kowdley ‐ Advisory Committees or Review Panels: Abbvie, Enanta, Gilead, Intercept, Merck, Novartis, Trio Health, Verylx; Grant/Research Support: Abbvie, Evidera, Galectin, Gilead, Immuron, Intercept, Merck, NGM Biopharma, Novartis, Tobira, Trio Health; Speaking and Teaching: Gilead, Intercept

Stuart C. Gordon ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Merck, Intercept; Consulting: CVS Caremark; Grant/Research Support: Cymba Bay, Gilead, BMS, AbbVie, Intercept, Conatus, Exalenz, Merck; Speaking and Teaching: Gilead, Intercept

The following people have nothing to disclose: Qiushi Chen, Turgay Ayer, Fasiha Kanwal, Xiaojie Wang, Mark S. Roberts

¹Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Kaohsiung, Taiwan; ²Institute of Clinical Medicine, National Yang‐Ming University, Taiwan, Taipei, Taiwan

Background/Aims Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by means of anti‐viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC) development. The current study aimed to compare the risk of HCC between the two patient groups Methods A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age‐ and sex‐matched patients in the treatment‐induced SVR group were enrolled for analysis. Results Nineteen (2.17%) of the 877 patients developed HCC during 6,963 person‐years of follow‐up. Fourteen (2.48%) SVR patients and 5 (1.6 %) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27‐26.88), diabetes (HR/ C1: 3.41/1.21‐9.58), and age (HR/CI: 1.07/1.01‐1.14). Of the 564 SVR patients, eleven (5.88 %) of the 187 patients with fibrosis stage 2‐4 (F2‐4) and 2 (0.88 %) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2‐4 (P<0.001) but not F0‐1(P=0.60) had a higher risk of HCC development Cox‐regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2‐4 (versus SC: HR/ CI: 10.06/2.20‐45.98), diabetes (HR/CI:3.23/1.14‐9.19), and age (HR/CI: 1.08 1.02‐1.15). Conclusions Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment‐induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision‐making regarding the prioritization of current direct antiviral agents in resource‐limited countries.

Disclosures:

Ming‐Lung Yu ‐ Advisory Committees or Review Panels: ABBOTT, MSD, ABBVIE, GILEAD, J&J, ROCHE, BMS; Consulting: MSD, ABBVIE, GILEAD, J&J, ROCHE, BMS; Grant/Research Support: ABBOTT, ROCHE, MSD, ABBVIE, GILEAD, ABB‐ VIE, GILEAD, ROCHE, BMS; Speaking and Teaching: ABBOTT, ROCHE, MSD, GILEAD, BMS, GSK

Wan‐Long Chuang ‐ Advisory Committees or Review Panels: Gilead, Abbvie, Roche, PharmaEssentia; Speaking and Teaching: Gilead, Roche, BMS, MSD, PharmaEssentia

The following people have nothing to disclose: Chung‐Feng Huang, Chia‐Yen Dai, Jee‐Fu Huang, Mei‐Hsuan Lee

Infectious Diseases, “Niguarda Ca Granda” Hospital, Milan, Italy

Background. HIV and HCV infections are characterized by chronic immune system activation that leads to immunologic dysregulation and exhaustion. This study assessed the evolution of inflammation parameters in HIV/HCV subjects treated with different anti‐HCV regimens Methods. Co‐infected individuals who started an interferon‐free treatment were included in the analysis Data about leukocytes, inflammation markers, cryoglobulins and autoantibodies were collected at baseline and 12 weeks after end of treatment. Descriptive statistics, Chi‐square and Wilcoxon tests were used. Results. 64 HIV/ HCV patients (males 76.6%, median age 52 years) achieved SVR12 after a treatment with different regimens, mainly sofosbuvir‐based (21.8% with SOF and ribavirin, 45.3% in combination with daclatasvir, 17.2% with ledipasvir, 9.4% with simeprevir), 6.3% with 3D The majority was infected by genotype 3 (37.5%) and was cirrhotic (68.8%). None had a diagnosis of autoimmune disease, 3 subjects had cryoglobulins‐related kidney damage There is a trend in Neutrophils increase, while no change was observed in Leukocytes, CD4+ and CD4/CD8 ratio. Ferritin and cryoglobulins positivity decrease significantly. Anti‐thyroglobulin, c‐ANCA and p‐ANCA decrease significantly. ANA positivity remains stable, but fluorescence changed: there is a trend in anti ring/ rod (anti‐RR) antibodies increase Conclusions. This analysis showed that achieving an SVR partially improves immunologic parameters within a short follow up: immunologic response in terms of cryoglobulins clearance was significant ANA showed a change in fluorescence was registered: anti‐RR antibodies are considered to be interferon‐induced, while in co‐infected subjects they were already present at baseline and increased with virologic clearance even without interferon, thus suggesting a virological clearance‐mediated instead of a drug‐induced effect.

Table 1. Comparison of immune‐related.

Disclosures:

The following people have nothing to disclose: Roberto Rossotti

¹Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA; ²Rush University Medical Center, Chicago, IL; ³Optum, Eden Prairie, MN

Background: Over 75% of patients living with CHC in the US were born between 1945 and 1965. As this population ages, the increasing rates of medical comorbidities will make CHC management more challenging In addition related medications and drug‐drug interactions may complicate the use of cytochrome P‐450 metabolized DAAs. Objective: To measure the prevalence of comorbidities and medications that may be barriers towards initiating DAAs in a large U S cohort with CHC. Methods: We identified from Optum Insight's insurance claims database CHC patients by ICD‐9 code from 1/1/2011 to 9/30/2015. Our treatment group consisted of patients receiving DAA prescriptions after 11/1/2013. Any patients treated prior to 11/1/2013 were excluded from the study. Medical comorbidities were defined by ICD‐9 codes. Results: In total, 12,622 insured CHC patients were included: 6,325 treated and 6,297 untreated patients The majority were male (61%) and had Medicare part‐D (66.8%). By medical comorbidities (Figure), untreated patients were more likely to have end stage renal disease (4% vs. 1.4% treated, OR = 2.9, p <0.001), congestive heart failure (11.4% vs. 4.4% treated, OR = 2.8, p < 0.001), and seizure disorder (5.6% vs 3% treated, OR = 1.9, p < 0.001). Untreated patients were also more likely to have active or prior episodes of psychosis (9.4% vs. 5% treated, OR = 2, p < 0.001) and were more likely to be prescribed a medication with potentially severe drug‐drug interaction to DAAs (24.7% vs. 21.5% treated, p < 0.001) including anticonvulsants (1.7% untreated vs. 0.9% treated, p < 0.001). Conclusion: In a largely Medicare U.S. cohort of CHC patients, the prevalence of certain major comorbidities and concomitant medications was higher in untreated CHC patients compared to treated patients The presence of major comorbidities and/ or concomitant medications with major drug‐drug interactions with anti‐HCV medications may be a barrier to anti‐HCV therapy, and treatment prior to development of such comorbidities and related medications may help improve the overall treatment rate for CHC.

Disclosures:

Mindie H. Nguyen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead; Consulting: Gilead Sciences, Inc. ; Grant/Research Support: Gilead Sciences, Inc., Bristol‐Myers Squibb

The following people have nothing to disclose: Philip Vutien, Nhu (Josephine) Q. Tran, Felix Cao, Vincent Peichel

Viral hepatitis/BCD, NYC DOHMH, Long Island City, NY

BACKGROUND: In New York City (NYC), many of the estimated 146,500 residents with chronic hepatitis C (HCV) will likely seek care at one of NYC's 34 acute care hospitals' outpatient clinics Data on the capacity of hospitals to provide HCV screening, diagnosis, and treatment are limited Given the changing landscape of HCV treatment and the complexity of the NYC hospital‐based healthcare system, an understanding of gaps related to HCV care is needed to tailor interventions To that end, the NYC Health Department conducted a needs assessment of hospitals on their capacity for HCV screening, diagnosis, and treatment METHODS: The Health Department developed and administered a survey on facility‐level practices related to HCV screening, diagnosis, and treatment capacity to NYC acute care hospitals Clinical representatives from the hospitals were recruited through email and site visits Responses were collected through paper surveys and SurveyMonkey. com from July 8, 2015 ‐ September 30, 2015. Descriptive analysis was conducted using Survey Monkey and Excel. RESULTS: Twenty‐seven hospitals completed the survey (79% response rate). Screening: Of the 23 hospitals responding to this question, 18 (78%) indicated that most of their patients have risk factors for HCV infection Eighteen (67%) of the 27 sites also reported that their hospital's electronic health record system had an age‐based screening alert for high‐risk patients born from 1945‐1965, yet only 10 (37%) reported screening 50% or more of this cohort. Diagnosis: Eleven (41%) sites reported no challenges to providing RNA testing in‐house, but only 5 (19%) had implemented HCV antibody‐to‐RNA reflex testing. Treatment: With the exception of one facility, all hospitals indicated being able to provide HCV treatment in‐house. However, only 9 (33%) and 6 (22%) respondents indicated that HCV treatment was available in their primary care clinics for mono‐infected and HIV/HCV co‐infected patients, respectively Most patients were cared for in infectious diseases and gastroenterology clinics. Finally, of the 26 hospitals responding to this question, 16 (62%) indicated denial of medication coverage by health insurances was a barrier to HCV treatment. CONCLUSION: This survey provided an understanding of practice and gaps in HCV care capacity among acute care hospital clinics in NYC. Low rates of screening, confirmatory testing, along with limited provider capacity in primary care settings and barriers to securing treatment were reported. This information is being used to guide the work of the HCV Clinical Network and develop interventions to address these gaps.

Disclosures:

The following people have nothing to disclose: Ryan Duerme, Shale Maulana, Jessie Schwartz, Nirah Johnson, Eric J. Rude, Fabienne Laraque

¹Medizinische Klinik I, Universitätsklinikum Frankfurt, Frankfurt, Germany; ²Medizinische Hochschule Hannover, Hannover, Germany; ³Covance Central Laboratory Services, Geneva, Switzerland; ⁴Roche Molecular Diagnostics, Pleasanton, CA

Background and Aim: Quantification of HCV RNA during antiviral therapy is essential for the guidance of treatment duration, to decide on futility and to determine sustained response. The aim of this study was to evaluate the performance of the recently FDA‐approved real‐time PCR HCV RNA assay cobas® HCV for use on the cobas® 6800/8800 systems (cobas HCV; Roche Diagnostics). Methods: Analytical sensitivity and linearity at lower concentrations (5‐1000 lU/mL) were assessed by cobas HCV using WHO standard traceable panels representing HCV genotypes (GT) 1‐4 and compared with two established HCV RNA assays, COBAS® AmpliPrep/COBAS® TaqMan® HCV test v2.0 (CAP/CTM) and COBAS® TaqMan® HCV test v2.0 for Use with the High Pure System (HPS/CTM) ln addition, pairwise assay comparisons were performed using clinical serum samples (n=245) representing HCV GT1. Concordance of baseline samples was assessed using the 6 million lU/mL cut‐off which is used to tailor treatment duration in non‐cirrhotic, treatment‐naive GT1 patients receiving ledipasvir/sofosbuvir. Results: The analytical sensitivity of cobas HCV was 8.2 lU/ mL (95% Cl: 6.7‐14.4) in samples representing GT 1, and 6.3, 6.1 and 13.7 lU/mL in GT 2, 3 and 4, respectively, cobas HCV was mostly linear at low HCV RNA concentrations with a mean observed log difference of 0.18 in samples containing GT1 (all differences between expected and observed results were <0.3 log lU/ml). Pairwise comparison of quantifiable GT 1 samples showed excellent agreement between cobas HCV and CAP/CTM (mean difference, 0.085; 95% Cl: 0.06, 0.11), and cobas HCV vs. HPS/CTM (mean difference, −0.095; 95% Cl: −0.119, −0.072). Using the concordance in baseline samples between cobas HCV vs CAP/CTM and cobas HCV vs HPS/CTM was 97% and 96%, respectively, with respect to the 6 million lU/mL cut‐off Conclusions: cobas HCV is highly sensitive and linear at the low end of the dynamic range in GTs 1‐4. cobas HCV shows excellent correlation and a high level of concordance at the 6 million cut‐off with CAP/CTM and HPS/ CTM in clinical samples of patients with HCV GT1.

Disclosures:

Johannes Vermehren ‐ Advisory Committees or Review Panels: AbbVie, Abbott; Speaking and Teaching: AbbVie, Bristol‐Myers Squibb, Gilead, Medtronic

Benjamin Maasoumy ‐ Advisory Committees or Review Panels: Abbott Molecular, Janssen‐Cilaq; Grant/Research Support: Abbott Molecular, Roche Diagnostics; Speaking and Teaching: MSD/Merck, Roche Diagnostics, Roche Pharma, Janssen‐Cilaq, Fujirebio, BMS, AbbVie

Enrique Marino ‐ Employment: Roche Molecular Systems, Inc

Ed G. Marins ‐ Employment: Roche Molecular Systems

Heiner Wedemeyer ‐ Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics, Eiger; Consulting: MyrGmbH; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics; Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

The following people have nothing to disclose: Caterina Berkowski, Veronique Michel‐Treil

¹The Kirby Institute, University of New South Wales, Sydney, NSW, Australia; ²St Vincent's Applied Medical Research, St Vincent's Hospital Sydney, Sydney, NSW, Australia; ³Abbott Virology, Abbott Laboratories, North Chicago, IL

Background: Simplified, affordable diagnostic tools are essential to facilitate global access to hepatitis C virus (HCV) treatment. This study evaluated the clinical performance of HCV core antigen (HCVcAg) detection as an alternative to RNA testing in plasma to monitor HCV treatment efficacy in recent infection. Methods: Participants with recent HCV infection (duration of infection ≤12months) who completed 6 weeks of sofosbuvir+ribavirin in DARE‐C II were assessed at week 1, 2, 3, 4, end of treatment (ETR) and post‐treatment week 4, week 12 and week 24. HCV RNA and HCVcAg were quantified by AmpliPrep/COBAS Taqman assay (Roche) and ARCHITECT HCV Ag (Abbott Diagnostics). The sensitivity and specificity of HCVcAg assay (>3fmol/L) were calculated for quantifiable HCV RNA (>15IU/mL). Results: 124 longitudinal samples in 18 treated participants were available for HCV RNA and HCVcAg testing, including baseline (n=18), ETR (n=16), post‐treatment week 12 (n=18). Overall, HCVcAg demonstrated a sensitivity of 74.1% (95% CI 60.7‐84.4) and a specificity of 98.5% (95% CI 90.799.9) compared with HCV RNA. At pre‐treatment, HCVcAg was detected in 89% samples, demonstrating a sensitivity of 88.9% (95% CI 63.9‐98.1). Two baseline HCVcAg non‐reactive samples had quantifiable HCV RNA at 33 and 150IU/ mL At ETR, RNA and HCVcAg were detected in 13% and 6% samples, respectively (sensitivity 50%, 95% CI 2.7‐97.3; specificity 100%, 95% CI 73.2‐100%). At post‐treatment week 12, RNA and HCVcAg were detected in 72% and 61% samples, respectively (sensitivity 84.6%, 95% CI 53.7‐97.3; specificity 100%, 95% CI 46.3‐100% CI). Two post‐treatment week 12 non‐reactive HCVcAg results had quantifiable HCV RNA at 50 and 2533IU/mL. Conclusion: This study demonstrates core antigen provides high specificity when compared with HCV RNA The potential clinical utility of HCV core antigen requires further evaluation, particularly in the context of low HCV RNA levels.

Disclosures:

Gavin A. Cloherty ‐ Employment: Abbott Laboratories; Stock Shareholder: Abbott Laboratories

Jason Grebely ‐ Advisory Committees or Review Panels: Merck, Gilead; Grant/ Research Support: Merck, Gilead, Abbvie, BMS

Gregory Dore ‐ Board Membership: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Grant/Research Support: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Gilead, Merck, Abbvie, Bristol‐Myers Squibb

The following people have nothing to disclose: Francois Lamoury, Behzad Hajarizadeh, Marianne Martinello, Angelica Soker, Danica Martinez, Philip Cunningham, Pip Marks, Gail Matthews, Janaki Amin, Tanya L Applegate

¹Gilead Sciences, Inc., Foster City, CA; ²Rush University Medical Center, Chicago, IL; ³Stanford University Medical Center, Palo Alto, CA; ⁴Swedish Medical Center, Seattle, WA; ⁵Auckland City Hospital, New Zealand Liver Transplant Unit, Auckland, New Zealand; ⁶University of Texas Health Sciences Center, Texas Liver Institute, San Antonio, TX; ⁷Mount Sinai Beth Israel, New York, NY; ⁸Indiana University School of Medicine, Indianapolis, IN; ⁹Beth Israel Deaconess Medical Center, Boston, MA

Background: In 4 Phase 2 studies, the combination of sofosbuvir (SOF), velpatasvir (VEL), and voxilaprevir (VOX) that target distinct HCV proteins, NS5B, NS5A, and NS3/4A, respectively, demonstrated high efficacy in genotype (GT) 1‐6 HCV infected patients who were DAA‐naïve or DAA‐experienced with durations of 8 or 12 weeks. Here, we evaluate the effect of baseline resistance associated substitutions (RASs) on treatment outcome and emergence of RASs in patients who experience virologic failure Methods: NS3, NS5A, and NS5B deep sequencing was performed at baseline for all patients (N=262; 145 GT1a, 31 GT1b, 23 GT2, 54 GT3, 7 GT4, 2 GT6) and at the time of virologic failure. Results are reported using a 15% cutoff. Results: At baseline, 141/262 (54%) patients had RASs in at least one of the NS3 and/or NS5A viral genes (23% NS3, 18% NS5A, 13% NS3/NS5A). NS5A RASs were observed more commonly in NS5A inhibitor‐experienced patients (40/46, 87%) than DAA‐experienced patients who had not previously received a NS5A inhibitor (18/81,22%). In DAA‐naïve patients treated for 8 weeks, 97% achieved SVR12 with similar SVR12 rates observed in patients without (79/81, 98%) or with (52/54, 96%) RASs. In NS5A inhibitor‐experienced patients, all (46/46, 100%) achieved SVR12 and in non‐NS5A inhibitor DAA‐experienced patients, all but 1 patient (80/81, 99%) with a NS5A RAS achieved SVR12. Overall, 91% of patients with NS5A Y93 RASs at baseline achieved SVR12 (21/23). Thirteen (5%) patients had NS5B nucleoside inhibitor (NI) RASs, including 5 with L159F, all achieved SVR12. Of the 5 patients who relapsed, none had treatment emergent NS5A and NS5B RASs. One patient who relapsed had treatment‐emergent NS3 Q80R (which confers no phenotypic change to VOX). Conclusions: Baseline RASs had no impact on the virologic response in DAA‐naïve and DAA‐experienced patients following treatment with SOF, VEL, and VOX for 8 or 12 weeks, respectively. Viral relapse was not associated with emergence of viral resistance.

SVR12 in Patients With or Without Baseline RASs

Disclosures:

Nancy Reau ‐ Advisory Committees or Review Panels: Jannsen, Merck, AbbVie, Intercept, Salix, BMS, Gilead; Grant/Research Support: Gilead, Intercept, Abb‐ Vie

Mindie H. Nguyen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead; Consulting: Gilead Sciences, Inc. ; Grant/Research Support: Gilead Sciences, Inc., Bristol‐Myers Squibb

Kris V. Kowdley ‐ Advisory Committees or Review Panels: Abbvie, Enanta, Gilead, Intercept, Merck, Novartis, Trio Health, Verylx; Grant/Research Support: Abbvie, Evidera, Galectin, Gilead, Immuron, Intercept, Merck, NGM Biopharma, Novartis, Tobira, Trio Health; Speaking and Teaching: Gilead, Intercept

Edward J. Gane ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead Sciences, Achillion, Merck; Speaking and Teaching: AbbVie, Gilead Sciences, Merck, Alnylam

Hadas Dvory‐Sobol ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Evguenia S. Svarovskaia ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

Jenny C. Yang ‐ Employment: Gilead Sciences, Inc Luisa M. Stamm ‐ Employment: Gilead Sciences

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Michael D. Miller ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Hongmei Mo ‐ Employment: Gilead Science Inc

Eric Lawitz ‐ Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals, Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol‐Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead, Janssen, AbbVie, Bristol Meyers Squibb, Merck, intercept

Paul Y. Kwo ‐ Advisory Committees or Review Panels: Abbott, Abbvie, BMS, Gilead, Janssen, Merck, Alnylam, Quest, CVS, Innovio; Grant/Research Support: Abbvie, BMS, Gilead, Merck, Janssen, Esai, Cepheid, Conatus

Michael P. Curry ‐ Consulting: Alexion, Bristol Meyers Squib, Abbvie; Grant/ Research Support: Gilead Sciences, Conatus

Ira M. Jacobson ‐ Consulting: AbbVie, Achillion, Bristol Myers Squibb, Intercept, Gilead, Janssen, Merck, Trek; Grant/Research Support: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck; Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen

¹Hannover Medical School, Hannover, Germany; ²HepNet Study‐House, project of the German Liver Foundation, Hannover, Germany; ³University Hospital Klinikum rechts der Isar, Munich, Germany; ⁴Charité Universitätsmedizin Berlin, Berlin, Germany; ⁵University Hospital Frankfurt, Frankfurt, Germany; ⁶University Hospital Essen, Essen, Germany; ⁷University of Würzburg Medical Center, Würzburg, Germany; ⁸University Hospital Bonn, Bonn, Germany; ⁹University of Leipzig, Leipzig, Germany; ¹⁰University Hospital Hamburg‐Eppendorf, Hamburg, Germany; ¹¹University Clinic of Heidelberg, Heidelberg, Germany; ¹²HepNet Study‐ House, project of the German Liver Foundation, German Centre for Infection Research (DZIF), Hannover, Germany; ¹³Hannover Clinical Trial Center GmbH, Hannover, Germany; ¹⁴Department of Biostatistics, Hannover, Germany

Background: Early treatment of acute hepatitis C virus (HCV) infection with interferon alfa monotherapy is highly effective but is associated with frequent unfavorable side effects. There is no fully published study yet exploring the safety, efficacy and required treatment duration of interferon free treatment of acute hepatitis C virus monoinfection. Preliminary reports suggested that ledipasvir/sofosbuvir therapy is effective in acute hepatitis C but relapses were reported in HIV‐coinfected patients after 6 weeks of treatment. Methods: The German HepNet Acute HCV IV Study was designed as a single arm, prospective multicenter pilot study to evaluate the efficacy and safety of treatment with sofosbuvir plus ledipasvir (SOF/LDV) for 6 weeks without ribavirin in patients with acute genotype 1 HCV monoinfection. We here report the final 24 weeks post treatment results. Results: Twenty patients were included by 10 centers (60% male, mean age 46±12 years; 11 patients HCV genotype 1a, 9 patients genotype 1b). The main risk factors for HCV infection were sexual transmission (n=11) and medical procedures/needle stick injuries (n=5). Median alanine aminotransferase (ALT) and median bilirubin levels before start of antiviral treatment were 225 U/l (range 32‐2716) and 13.6 ^mol/l (range 5.13‐111), respectively ALT levels rapidly declined during therapy and values normalized already by treatment weeks 2 in 9 patients and by week 4 in 17 patients. HCV RNA was undetectable by the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0 by weeks 2, 4 and 6 in 8, 13, and 20 patients, respectively. SVR‐12 was 100% and 18 patients have already completed FU‐week 24 and all remained HCV‐RNA negative. Conclusion: Treatment for 6 weeks with LDV/SOF was well tolerated and highly effective in HCV genotype 1 monoinfected patients with acute hepatitis C. Virological response was durable after therapy for at least 24 weeks. A rapid improvement in biochemical disease activity was observed during therapy. Short‐duration treatment of acute hepatitis C could prevent the spread of HCV in high risk populations and may be cost‐saving as compared to treatment of chronic hepatitis C.

Disclosures:

Katja Deterding ‐ Speaking and Teaching: AbbVie, MSD/Merck, Gilead

Christoph D. Spinner ‐ Advisory Committees or Review Panels: Gilead Sciences; Grant/Research Support: Gilead Sciences

Eckart Schott ‐ Advisory Committees or Review Panels: Gilead, Roche, Bayer, BMS, Abbvie, Janssen, MSD; Speaking and Teaching: Gilead, Novartis, Roche, MSD, Bayer, Falk, BMS, Janssen, Abbvie

Tania M Welzel ‐ Advisory Committees or Review Panels: Novartis, Janssen, Gilead, Abbvie, Boehringer‐Ingelheim+, BMS

Hartwig H Klinker ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, Hexal, Janssen, MSD; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, MSD, Arrowhead, Novartis; Speaking and Teaching: AbbVIe, BMS, Gilead, Janssen, MSD

Anita Pathil ‐ Speaking and Teaching: AbbVie, BMS, Gilead

Markus Cornberg ‐ Advisory Committees or Review Panels: Merck (MSD Ger‐

mamny), Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research

Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD

Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie

Andreas Umgelter ‐ Speaking and Teaching: Gilead, BMS

Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

Michael P Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

Heiner Wedemeyer ‐ Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics, Eiger; Consulting: MyrGmbH; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics; Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead

The following people have nothing to disclose: Guido Gerken, Ulrich Spengler, Johannes Wiegand, Julian Schulze zur Wiesch, Caroline Zöllner, Armin Papkalla, Kristina Weber, Svenja Hardtke, Heiko von der Leyen, Armin Koch, Dorothee von Witzendorff

¹UCLA, Los Angeles, CA; ²Baylor Health, Fort Worth, TX; ³Stanford University Medical Center, Palo Alto, CA; ⁴Roger Williams Medical Center, Providence, RI; ⁵Inova Fairfax Hospital, Falls Church, VA

Background and Objective: Selected all‐oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating Hepatitis C (HCV) patients with decompensated cirrhosis (DCC) However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre‐ vs. post‐liver transplant (LT). The objective of this study was to analyze the cost‐effectiveness of pre‐ vs. post LT treatment with an all‐oral DAA regimen among patients with DCC waitlisted (WL) for LT. Methods: We constructed a decision‐analytic Markov model of the natural disease progression of HCV in patients with decompensated cirrhosis (DCC) waitlisted (WL) for LT. The model followed a hypothetical cohort of 1,000 patients with a mean age of 50 over a lifetime horizon from a third‐party US payer perspective, and estimated their health and cost outcomes based on pre‐ vs. post‐LT treatment with an oral DAA. Health states and natural history pre‐LT were stratified by MELD score and SVR Transition probabilities and utilities were based on the literature and hepatologist consensus. SVR rates were sourced from ASTRAL‐4 and SOLAR‐1, ‐2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. Results: The post‐LT treatment arm had a mean time on WL of 0.94 years and a 27.6% probability of death on the WL, vs. 2.05 years (+117.5%) and 26.2% (−5.1%) in the pre‐LT arm. Over the model time horizon, the post‐LT treatment arm yielded 629 patients with SVRs, 7 patients with HCC, and 679 liver‐related deaths, vs. 902 (+43.4%), 5 (+35.8%) and 607 (−10.7%) in the pre‐LT arm. The pre‐LT treatment strategy resulted in 10.2 per‐patient quality‐adjusted life years (QALYs), 12.0 per patient life years (LYs), and $262,846 per patient lifetime costs vs. 9.0, 11.3, and $253,713 in the post‐LT arm. Therefore, pre‐LT treatment was found to be the most cost‐effective, with an ICER of $7,593. Based on one‐way deterministic sensitivity analysis, our results were most sensitive to the utility of patients post‐LT, treatment SVR rates, and LT costs. Conclusion: The timing of antiviral treatment for HCV patients with DCC relative to LT is an important area of clinical and policy research. Our results indicate that pre‐LT treatment with a highly effective, all‐oral DAA regimen is the most cost‐effective strategy for the treatment of HCV patients with DCC waitlisted for LT.

Disclosures:

Sammy Saab ‐ Advisory Committees or Review Panels: BMS, Gilead, Merck, Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead, Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion, Johnson and Johnson, BMS, Gilead

Stevan A. Gonzalez ‐ Speaking and Teaching: Gilead, Salix, AbbVie, Merck

Aijaz Ahmed ‐ Consulting: Bristol‐Myers Squibb, Gilead Sciences Inc., Roche, AbbVie, Shire, Janssen pharmaceuticals; Grant/Research Support: Gilead Sciences Inc

The following people have nothing to disclose: Ryan B Perumpail, George Cholankeril, Zobair M. Younossi

AbbVie, North Chicago, IL

Background: ABT‐493 (NS3/4A protease inhibitor [PI] identified by AbbVie and Enanta) and ABT‐530 (NS5A inhibitor) are next generation HCV direct‐acting antiviral agents (DAAs) Co‐administration of ABT‐493 + ABT‐530 achieved a high sustained virologic response 12 (SVR12) rate in DAA‐naïve patients with HCV genotype (GT) 1‐6 infection, as well as GT1‐infected patients who had previously failed a DAA‐containing regimen. In this report we present the characterization of variants detected in samples from subjects enrolled in Part 1 of the MAGELLAN‐1 study: treatment with ABT‐493 + ABT‐530 ± RBV for 12 weeks in non‐cirrhotic GT1‐infected patients who had previously failed regimens containing a PI and/or NS5A inhibitor, ± an NS5B polymerase inhibitor. Methods: Next generation sequencing (NGS) was performed on HCV NS3/4A and NS5A genes from all baseline samples and the first available sample after virologic failure with HCV RNA ≥1000 IU/ mL. Sequencing results at 1% and 15% detection cutoffs were examined for the presence of resistance‐associated variants (RAVs) in the NS3 and NS5A genes. Results: NGS (with 1% cutoff) of baseline samples from all patients (n=50) identified RAVs in 41 (82%) patients: 15 (30%) in NS3 only, 10 (20%) in NS5A only, and 16 (32%) in both targets. In 90% (37/41) of these samples, the RAVs were also present using an NGS detection cutoff of 15% These DAA‐experienced patient cohorts had broad representation of baseline variants at key resistance‐associated positions, including those at NS3 V36, Q80, R155, and D168, as well as NS5A M28, Q30, L31, and Y93 All patients with baseline variants at position Y93 in NS5A that confer high level of resistance to currently approved NS5A inhibitors achieved SVR12 (n=10). Of the 2 out of 50 (4%) patients who experienced virologic failure, 1 patient had baseline NS3 (Y56H and D168A/T) and NS5A (M28V and Q30L/R) RAVs, and the other patient had baseline RAVs in NS5A (L31M and H58D) only. Conclusions: The combination of ABT‐493 and ABT‐530 demonstrated potent antiviral activity and a high barrier to resistance in non‐cirrhotic HCV GT1‐in‐ fected patients who had previously failed a DAA‐containing regimen, regardless of the diverse profile and high prevalence of baseline NS3 and/or NS5A RAVs among these patients. These promising results support the study of this combination regimen in a larger cohort of DAA‐experienced patients.

Disclosures:

Teresa Ng ‐ Employment: AbbVie; Patent Held/Filed: AbbVie; Stock Shareholder: AbbVie

Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott

Rakesh Tripathi ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Gretja Schnell ‐ Employment: AbbVie Inc. ; Stock Shareholder: AbbVie Inc.

Thomas Reisch ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Jill Beyer ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Tanya Dekhtyar ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Armen Asatryan ‐ Employment: AbbVie

Federico Mensa ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Jens Kort ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Christine Collins ‐ Employment: AbbVie

¹Stanford University Medical Center, Stanford, CA; ²UCLA, Los Angeles, CA; ³Henry Ford Hospital, Detroit, MI; ⁴Icahn School of Medicine, New York, NY; ⁵South Denver Gastroenterology, Englewood, CO; ⁶Inova Fairfax Hospital, Falls Church, VA

BACKGROUND AND AIM: Chronic hepatitis C virus (CHC) patients with decompensated cirrhosis (DCC) awaiting transplant have limited treatment options and are at high risk for liver‐related comorbidity and increased mortality The new oral single tablet regimen of sofosbuvir/velpatasvir (SOF/VEL) has been shown to have excellent efficacy and safety in this population A decision‐analytic Markov model evaluated the health outcomes of SOF/VEL compared with current treatment options in DCC. METHODS: The analysis modeled a cohort of 10,000 CHC DCC genotype (GT) 1‐6 patients with an average age of 52 from a US third‐party payer perspective over a lifetime horizon. Pre‐transplant treatment with SOF/VEL for 12 weeks (W) with ribavirin (R) was compared with ledipasvir/sofosbuvir (LDV/SOF) 12W+R and 24W+/‐R, SOF+ daclatasvir (DCV) for 12W+R or 24W, and no treatment (NT). Sustained virologic response (SVR) rates were extrapolated from ASTRAL‐4, SOLAR‐1, ‐2, and ALLY‐1. Transition probabilities and utilities were based on a literature review and consensus by a panel of hepatologists. RESULTS: The SOF/VEL regimen resulted in the best health outcomes in terms of the lowest number of hepatocellular carcinoma (HCC) cases, liver transplants (LT), and liver‐related deaths compared with all comparators in GT 1, 2, 3, and 5/6 (Table 1). In GT4, SOF+DCV was associated with slightly fewer liver‐related complications, particularly for HCC and LT. CONCLUSIONS: Compared to currently available options including SOF+DCV, LDV/SOF and NT, SOF/VEL demonstrated better overall health outcomes in DCC patients, leading to fewer cases of liver‐related complications Further, SOF/VEL is the only available pan‐genotypic, all‐oral, once‐ daily single tablet regimen for CHC patients, simplifying treatment across GTs.

Table 1. Projected health outcomes perl0,000 patientsforSOF/VELvs. comparators

Disclosures:

Aijaz Ahmed ‐ Consulting: Bristol‐Myers Squibb, Gilead Sciences Inc., Roche, AbbVie, Shire, Janssen pharmaceuticals; Grant/Research Support: Gilead Sciences Inc

Sammy Saab ‐ Advisory Committees or Review Panels: BMS, Gilead, Merck, Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead, Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion, Johnson and Johnson, BMS, Gilead

Stuart C Gordon ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Merck, Intercept; Consulting: CVS Caremark; Grant/Research Support: Cymba Bay, Gilead, BMS, AbbVie, Intercept, Conatus, Exalenz, Merck; Speaking and Teaching: Gilead, Intercept

Douglas T Dieterich ‐ Advisory Committees or Review Panels: Gilead, BMS, Abbvie, Janssen, Merck, Achillion

Robert J. Wong ‐ Advisory Committees or Review Panels: Gilead; Grant/ Research Support: Gilead

Kimberly Ann Brown ‐ Advisory Committees or Review Panels: CLDF, gilead, abbvie, janssen, Merck, BMS, Janssen; Grant/Research Support: Gilead, abbvie, janssen, duke medical research, Merck; Speaking and Teaching: CLDF

Marcelo Kugelmas ‐ Advisory Committees or Review Panels: Merck, Abbvie, Janssen, Salix; Consulting: Abbvie, Merck, Gilead, Janssen; Grant/Research Support: roche, Intercept, Hologic, Gilead, Janssen, Roche, Anadys, Salix, abbvie; Speaking and Teaching: Abbvie, Gilead, Merck, Janssen, Salix

The following people have nothing to disclose: Zobair M. Younossi

Department of Hepatology, Toranomon Hospital, Tokyo, Japan; ²Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan; ³Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan; ⁴Department of Hepatology, Osaka City University Medical School, Osaka, Japan; ⁵Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Osaka, Japan; ⁶Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; ⁷Department of Gastroenterology & Hepatology, Saitama Medical University, Saitama, Japan; ⁸Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan; ⁹Third Department of Internal Medicine, Nara Medical University, Nara, Japan; ¹⁰Department of Gastroenterology/Liver Center, Hiroshima Red Cross Hospital and Atomic‐bomb Survivors Hospital, Hiroshima, Japan; ¹¹MSD K.K., Tokyo, Japan; ¹²Merck & Co., Inc., Kenilworth, NJ

Introduction: This phase 3 portion of a phase 2/3 study assessed an all‐oral, once‐daily regimen of elbasvir (EBR, MK‐8742; HCV NS5A inhibitor) in combination with grazoprevir (GZR, MK‐5172; HCV NS3/4A protease inhibitor) in treatment‐naive or IFN‐experienced Japanese patients with or without compensated cirrhosis with HCV genotype 1 (GT1) infection. Methods: HCV GTl‐infected non‐cirrhotic patients were randomized to immediate treatment with EBR/GZR (50mg/100mg) once daily for 12 weeks or deferred treatment (placebo for 12 weeks followed by active dosing for 12 weeks) Compensated cirrhotic patients were assigned to receive open‐label EBR/GZR (50mg/100mg). The primary efficacy endpoint was sustained virologic response (SVR) at follow‐up week (FU) 12 (SVR12; COBAS TaqMan v2. 0 [lower limit of quantitation < 1.2 Log IU/mL]) in the EBR/GZR arm. Safety was evaluated with comparison of adverse events and laboratory abnormalities during treatment through FU4 in the immediate and deferred treatment arms. Results: 336 patients randomized (non‐cirrhotics: 227 received EBR/GZR and 74 received placebo, 36% male, mean age 61, and 98% GT1b; cirrhotics: n=35, 51% male, mean age 65, and 97% GT1 b). SVR12 on EBR/GZR was 96% (219/227) among non‐cirrhotics and 97% (34/35) among cirrhotics In the EBR/ GZR non‐cirrhotic arm 4% (8/227) did not achieve SVR12; 3 patients withdrew from the study before FU12 and 5 subjects relapsed. In the cirrhotic arm 3% (1/35) experienced relapse. During the initial treatment period through FU4, at least one AE occurred in 147 (65%) and 50 (68%) patients in the EBR/GZR non‐cirrhotic and placebo arms, respectively, and in 28 (80%) of cirrhotics. Serious AEs occurred in 11 (5%) and in 1 (1%) of the EBR/GZR non‐cirrhotic and placebo patients, respectively, and in no cirrhotic patients. Grade 3 and Grade 4 ALT elevations were observed for 1.3% (3/227) and 0.4% (1/227) in the EBR/GZR arm, but not in the placebo arm Grade 3 ALT elevations were observed for 5.7% (2/35) in the cirrhotic arm, but no patient had a Grade 4 ALT elevation The most common AEs were nasopharyngitis (15%) and ALT increased (5.7%) in EBR/GZR arm, and nasopharyngitis (14%) and ALT/ AST increased (14%) in the cirrhotic arm. SVR12 data from deferred treatment and SVR24 data will be also presented at the meeting. Conclusions: Once‐daily EBR/GZR for 12 weeks was highly effective and generally well tolerated in non‐cirrhotic and compensated cirrhotic Japanese patients with HCV G1‐infection.

Disclosures:

Fumitaka Suzuki ‐ Speaking and Teaching: BMS

Yoshiyasu Karino ‐ Speaking and Teaching: BMS KK

Kazuaki Chayama ‐ Advisory Committees or Review Panels: Mitsubishi Tanabe, Taisho Toyama; Consulting: AbbVie; Grant/Research Support: Ajinomoto, Abb‐ Vie, Aska, Asstellas, Aska, Bristol Squibb, Daiichi Sankyo, Dainippon Sumitomo, Daiichi Sankyo, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Nippon Kayaku, Otsuka, Sogo Rinsho M√©dV©fi, Taiho, Takeda, Toray, Torii, Tsumura, Zeria; Speaking and Teaching: Abbott, AbbVie, Ajinomoto, Astellas, AstraZeneca, Bayer, Bristol Squibb, Chugai, Dainippon Sumitomo, Eidia, Eisai, Gilead, GlaxoSmithKline, JIMRO, Johnson & Johnson, Mitsubishi Tanabe

Norifumi Kawada ‐ Grant/Research Support: Chugai; Speaking and Teaching: MSD, BMS, Gilead, Abbvie

Yoshito Itoh ‐ Grant/Research Support: Merk Sharp & Dohme, Bristol‐Myers Squibb Company, Gelaed Sciences Inc, Abbvie Inc., ONO PHARMACEUTICAL CO., LTD, Eisai Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., AJINOMOTO PHARMACEUTICALS CO., LTD., Sumitomo Dainippon Pharma Co., Ltd., FUJIFILM Medical Co., Ltd., Otsuka Pharmaceutical Co., Ltd.; Speaking and Teaching: Merk Sharp & Dohme, Bristol‐Myers Squibb Company, Gelaed Sciences Inc, Abbvie Inc.

Satoshi Mochida ‐ Grant/Research Support: Chugai, MSD, Tioray Medical, BMS, Dainihon Sumitomo Pharm, Ajinomoto Phamr, Abbvie, A2 Health Care Co, Eisai; Speaking and Teaching: MSD, Toray Medical, BMS, Tanabe Mitsubishi, Dainihon Sumitomo Pharm, Ajinomoto Pharm, Gilead, Abbvie

Naoyoshi Yatsuzuka ‐ Employment: MSD K K

tsuo Yodoya ‐ Employment: MSD K. K.

Go Fujimoto ‐ Employment: MSD K. K.; Stock Shareholder: Merck

Janice Wahl ‐ Employment: Merck & Co,

Michael Robertson ‐ Employment: Merck; Stock Shareholder: Merck Stuart Black ‐ Employment: Merck

Hiromitsu Kumada ‐ Speaking and Teaching: Bristol‐Myers Squibb,Pharma International, MSD, Abbvie, Glaxosmithkline, Gilead Sciences, Diainippon Sumitomo Pharma

The following people have nothing to disclose: Takeshi Okanoue, Hidenori Toyoda, Hitoshi Yoshiji, Shintaro Takaki

¹Gilead Sciences, Inc, Foster City, CA; ²Johns Hopkins University School of Medicine, Baltimore, MD; ³Veteran Affairs Medical Center, New York, NY; ⁴Icahn School of Medicine at Mount Sinai, New York, NY; ⁵University of California, San Diego, Division of Infectious Diseases, San Diego, CA

Background: Administration of the pangenotypic fixed‐dose combination of sofosbuvir (SOF)/velpatasvir (VEL) 400/100 mg once‐daily for 12 weeks resulted in an overall SVR12 rate of 95% (99/104) in HCV/HIV co‐infected subjects (ASTRAL‐5), which included subjects on boosted (cobicistat‐ or ritonavir‐containing) or unboosted antiretroviral (ARV) regimens Pharmacokinetic (PK) data were collected to evaluate the relationship between exposure and extrinsic/intrinsic variables, treatment outcome, and to compare PK in co‐infected and HCV mono‐infected subjects Methods: The study population included HCV/ HIV co‐infected subjects (N=106) receiving SOF/VEL 400/100 mg for 12 weeks on a stable ARV regimen including various combinations of: abacavir, atazanavir, cobicistat, darunavir, elvitegravir, emtricitabine, lamivudine, lopinavir, raltegravir, rilpivirine, ritonavir, and tenofovir disoproxil fumarate (TDF). The PK of SOF, GS‐331007, VEL, and tenofovir (TFV) were evaluated in all subjects with measurable plasma concentrations using previously established population PK models. The PK of SOF, GS‐331007, and VEL in HCV/HIV co‐infected subjects was compared across ARV regimen, treatment outcome, and to subjects with HCV monoinfection. The PK of TFV was compared across ARV regimens (boosted vs unboosted) Results: Exposures of SOF, GS‐331007, and VEL were similar across ARV regimens, and were similar to exposures observed in the HCV mono‐infected population (90% CI range: 0.76 to 1.10). Mean TFV exposure was similar following administration of SOF/VEL with a boosted (AUC_tau: 3740 h*ng/mL; n=56) or unboosted (AUC_tau: 3590 h*ng/mL; n=35) regimen, and was similar to mean TFV AUC observed following TDF administration as part of boosted regimens in HIV mono‐infected subjects (mean TFV AUC range: 3110 to 4630 h*ng/ mL) Conclusions: Pharmacokinetic results in addition to safety and efficacy data support the use of SOF/VEL 400/100 mg for 12 weeks in subjects with HCV/HIV co‐infection. Tenofovir exposures (administered as TDF) were consistent with those observed following administration of boosted regimens to HIV mono‐infected subjects.

Disclosures:

Erik Mogalian ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

Vinay Daryani ‐ Employment: Gilead Sciences, Inc

Anu O. Osinusi ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

John McNally ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

David L. Wyles ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, AbbVie; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb, AbbVie, Tacere

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Anita Mathias ‐ Employment: Gilead Sciences Inc.,

The following people have nothing to disclose: Liyun Ni, Norbert Bräu, John Ling

¹Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan; ²Department of Hepatology, Toranomon Hospital, Tokyo, Japan; ³Department of Gastroenterology, Sapporo Kosei General Hospital, Hokkaido, Japan; ⁴Department of Gastroenterology and Metabolism, Hiroshima University, Hiroshima, Japan; ⁵MSD K.K., Tokyo, Japan; ⁶Merck & Co., Inc., Kenilworth, NJ

Introduction: A Phase 2/3 clinical study was conducted to evaluate efficacy and safety of elbasvir (EBR, MK‐8742; HCV NS5A inhibitor (NS5A I)) and grazoprevir (GZR, MK‐5172; HCV NS3/4A protease inhibitor (NS3/4A PI)) in treatment‐naïve or ‐IFN experienced Japanese patients with or without compensated cirrhosis with HCV genotype 1 (GT1) infection Study results showed that once daily co‐administration of EBR/GZR for 12 weeks is highly effective and well tolerated in HCV GTl‐infected Japanese patients. The prevalence of HCV NS3 or NS5A resistance‐associated variants (RAVs) at baseline (BL) and their impact on SVR were also assessed in the study Methods: Population sequencing of NS3/4A and NS5A was performed on BL samples from all patients and on samples (viral load >3 Log IU/mL) from patients who met the criteria for virologic failure (VF) RAVs of interest that confer resistance to the NS3 protease inhibitor class include those at positions: 36, 54, 55, 56, 80, 107, 122, 132, 155, 156, 158, 168, 170 and 175. RAVs of interest that confer resistance to the NS5A inhibitor class include those at positions: 28, 30, 31, 58 and 93. In addition, selected samples were analyzed by clonal sequencing (≥40 clones, cutoff:5%); baseline samples from all patients and samples from VF patients in the phase 3 program were analyzed by next generation sequencing (NGS, cutoff: 1 %, 15%). The resistance analysis population (RAP) excluded non‐VFs (2 early discontinuations (ED) and 1 lost to follow‐up (LTFU)) as well as all patients in the placebo arm. Results: 324 patients received active study drug: 319 (98%) had GT1b and 5 (2%) had GT1a. 61/62 (98%, VF:1) and 253/262 (97%, VF:6, ED:2, LTFU:1) patients achieved SVR12 in the phase 2 and 3 portions of the study, respectively The prevalence of BL NS3 RAVs was 32% (103/321). All 103 patients achieved SVR12 including 5 patients (2%) with the BL D168E RAV. The prevalence of BL NS5A RAVs was 18% (58/321); 4% (13/321) at L31I/M/V and 14% (44/321) at Y93C/H. SVR12 was achieved in 93% (54/58) of patients with BL NS5A RAVs and 99% (260/263) of patients without BL NS5A RAVs. SVR12 was achieved in 92% (12/13) patients with BL L31I/M/V RAVs and 93% (41/44) patients with BL Y93C/H RAVs No treatment‐emergent NS3 RAVs were observed in the 7 VF Treatment‐emergent NS5A RAVs were observed in 6/7 VF including 4 patients who had BL NS5A RAVs that were still present at time of failure Conclusions: The prevalence of NS3 and NS5A RAVs that confer potency losses to various NS3/4A PIs and NS5A Is at baseline was 32% and 18%, respectively. The presence of these BL RAVs had no clinically remarkable impact on SVR12 in this Japanese phase 2/3 study.

Disclosures:

Yoshito Itoh ‐ Grant/Research Support: Merk Sharp & Dohme, Bristol‐Myers Squibb Company, Gelaed Sciences Inc, Abbvie Inc., ONO PHARMACEUTICAL CO., LTD, Eisai Co., Ltd., DAIICHI SANKYO COMPANY, LIMITED, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., AJINOMOTO PHARMACEUTICALS CO., LTD., Sumitomo Dainippon Pharma Co., Ltd., FUJIFILM Medical Co., Ltd., Otsuka Pharmaceutical Co., Ltd.; Speaking and Teaching: Merk Sharp & Dohme, Bristol‐Myers Squibb Company, Gelaed Sciences Inc, Abbvie Inc.

Fumitaka Suzuki ‐ Speaking and Teaching: BMS

Yoshiyasu Karino ‐ Speaking and Teaching: BMS KK

Kazuaki Chayama ‐ Advisory Committees or Review Panels: Mitsubishi Tanabe, Taisho Toyama; Consulting: AbbVie; Grant/Research Support: Ajinomoto, Abb‐ Vie, Aska, Asstellas, Aska, Bristol Squibb, Daiichi Sankyo, Dainippon Sumitomo, Daiichi Sankyo, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Nippon Kayaku, Otsuka, Sogo Rinsho M√©dV©fi, Taiho, Takeda, Toray, Torii, Tsumura, Zeria; Speaking and Teaching: Abbott, AbbVie, Ajinomoto, Astellas, AstraZeneca, Bayer, Bristol Squibb, Chugai, Dainippon Sumitomo, Eidia, Eisai, Gilead, GlaxoSmithKline, JIMRO, Johnson & Johnson, Mitsubishi Tanabe

Naoyoshi Yatsuzuka ‐ Employment: MSD K. K.

Etsuo Yodoya ‐ Employment: MSD K. K.

Go Fujimoto ‐ Employment: MSD K. K.; Stock Shareholder: Merck

Stuart Black ‐ Employment: Merck

Ernest Asante‐Appiah ‐ Employment: Merck

Janice Wahl ‐ Employment: Merck & Co,

Michael Robertson ‐ Employment: Merck; Stock Shareholder: Merck

Hiromitsu Kumada ‐ Speaking and Teaching: Bristol‐Myers Squibb,Pharma International, MSD, Abbvie, Glaxosmithkline, Gilead Sciences, Diainippon Sumitomo Pharma

AbbVie, North Chicago, IL

Purpose: The direct acting antiviral (DAA) combination of ABT‐ 493 (NS3/4A protease inhibitor discovered by AbbVie and Enanta) + ABT‐530 (NS5A inhibitor) achieved high sustained virologic response rates across chronic hepatitis C virus (HCV) genotype 1‐6 infection in Phase 2 studies with a favorable safety profile Angiotensin II receptor blockers (ARBs) are used in the treatment of hypertension and other cardiovascular indications, and are commonly administered in HCV infected subjects with such comorbidities Pharmacokinetics, safety, and tolerability of ABT‐493 + ABT‐530 coadministered with losartan or valsartan were evaluated to assess the drug‐drug interaction potential of these agents. Methods: This was an open‐label one‐sequence crossover study. Healthy adult subjects received single doses of losartan 50 mg (n=l2) or valsartan 80 mg (n=12) alone and in combination with ABT‐493 300 mg QD + ABT‐530 120 mg QD. Intensive blood sampling for determination of losartan, losartan carboxylic acid metabolite, valsartan, ABT‐493 and ABT‐530 concentrations was performed and pharmacokinetic parameters (maximum observed concentration [C_max], area under the concentration‐time curve [AUC_inf or AUC₂₄] and/or trough concentration [C₂₄]) were estimated. The effect of ABT‐493 + ABT‐530 on the pharmacokinetics of losartan or valsartan and vice versa, were assessed by a repeated‐measures analysis using SAS Safety was evaluated by assessment of adverse events, vital signs, ECGs, and clinical laboratory tests. Results: Exposures were higher for losartan (↑C_max 151% and ↑AUC_inf 56%) when administered with multiple doses of ABT‐493 + ABT‐530, relative to losartan alone; losartan active carboxylic metabolite C_max was 118% higher, while AUC_inf was similar (≤ 14% difference). Exposures of valsartan were slightly higher (↑C_max 36% and ↑AUC_inf 31%) when administered with ABT‐493 + ABT‐530. Exposures of ABT‐493 and ABT‐530 (C_max, AUC₂₄, and C₂₄) were similar with or without losartan or valsartan (≤ 23% difference). No serious adverse events occurred in the study. There was no pattern to the adverse events reported. No clinically significant vital signs, ECGs, or laboratory abnormalities were observed in the study. Conclusions: ABT‐493 + ABT‐530 increased losartan and valsartan exposures. ABT‐493 and ABT‐530 exposures were not affected by losartan or valsartan. Consistent with losartan and valsartan label recommendations for similar magnitudes of exposure increases caused by other drugs or in special populations, no dose adjustment is required when ABT‐493 and ABT‐530 are coadministered with losartan or valsartan.

Disclosures:

Matthew P. Kosloski ‐ Employment: AbbVie

Sandeep Dutta ‐ Employment: AbbVie

Qi Jiang ‐ Employment: AbbVie Inc.

Betty Yao ‐ Employment: AbbVie

Armen Asatryan ‐ Employment: AbbVie

Federico Mensa ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Jens Kort ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Wei Liu ‐ Employment: AbbVie

AbbVie, North Chicago, IL

Purpose: The direct acting antiviral (DAA) combination of ABT‐ 493 (NS3/4A protease inhibitor discovered by AbbVie and Enanta) + ABT‐530 (NS5A inhibitor) demonstrated favorable safety profiles and high sustained virologic response rates across chronic hepatitis C (HCV) genotype 1‐6 infection in Phase 2 studies It has been previously demonstrated that no dose adjustment is needed for administration of this combination in subjects with mild, moderate, or severe renal impairment, or with end‐stage renal disease (ESRD) not on dialysis. This study evaluated the pharmacokinetics and safety of ABT‐ 493 and ABT‐530 when administered in ESRD dialysis‐dependent subjects under dialysis and non‐dialysis conditions Methods: In this open‐label study, N=8 subjects on hemodialysis for ≥ 1 month received single doses of ABT‐493 300 mg + ABT‐530 120 mg in Period 1 three hours prior to initiating a hemodialysis session and in Period 2 on the day prior to scheduled hemodialysis. A washout of ≥ 7 days separated dosing in each period Intensive blood sampling for determination of ABT‐493 and ABT‐530 concentrations was performed for 24 hours following each dose and pharmacokinetic parameters (maximum observed concentration [C_max], area under the concentration‐time curve [AUC_t], clearance [CL], and clearance due to dialysis [CL_D]) were estimated. Additionally, arterial (predialyzer) and venous (postdialyzer) blood samples were collected during dialysis. The effect of dialysis on ABT‐493 and ABT‐530 pharmacokinetics was assessed by a repeated‐measures analysis. Safety was evaluated throughout the study with assessment of adverse events, vital signs, ECGs and clinical laboratory tests. Results: Peak plasma concentrations of ABT‐ 493 and ABT‐530 were both reached during dialysis. The mean dialysis duration was 3.95 hours C_max and AUC_t were similar for ABT‐493 (≤ 7% difference) and ABT‐530 (≤ 18% difference) under dialysis conditions compared to non‐dialysis days. ABT‐493 and ABT‐530 arterial and venous concentration profiles were similar during dialysis CL_D represented a minimal portion of total drug clearance for ABT‐493 (< 1%) and ABT‐530 (< 0.005%). No serious adverse events occurred in the study. No clinically significant vital signs, ECG or laboratory measurements were observed during the course of the study. Conclusions: ABT‐493 and ABT‐530 exposures were not affected by dialysis. No dose‐adjustment is needed when ABT‐ 493 + ABT‐530 are administered in subjects with renal impairment, with or without dialysis.

Disclosures:

Matthew P Kosloski ‐ Employment: AbbVie

Sandeep Dutta ‐ Employment: AbbVie

Weihan Zhao ‐ Employment: AbbVie, Inc; Stock Shareholder: AbbVie, Inc, United Airlines, American Airlines, Procter & Gamble

Federico Mensa ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Jens Kort ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Wei Liu ‐ Employment: AbbVie

The following people have nothing to disclose: David Pugatch

¹Inova Fairfax Hospital, Falls Church, VA; ²Henry Ford Hospital, Detroit, MI; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴South Denver Gastroenterology, Denver, CO; ⁵UCLA, Los Angeles, CA; ⁶Stanford University Medical Center, Palo Alto, CA

BACKGROUND AND AIM: Sofosbuvir / velpatasvir (SOF/ VEL) is an oral single tablet regimen that has been shown in the clinical trial setting to have excellent efficacy and tolerability in treatment‐naive (TN) and treatment‐experienced (TE) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1). A decision‐analytic Markov model evaluated the health outcomes of SOF/VEL compared with current treatment options for GT1. METHODS: The analysis modeled two cohorts of 10,000 chronic HCV GT1 patients (non‐cirrhotic (NC); cirrhotic (CC)) with an average age of 52 from a US third‐party payer perspective over a lifetime horizon 70% of each cohort was TN SOF/VEL for 12W was compared with LDV/SOF for 8W, 12W +/− ribavirin (RBV), and 24W, elbasvir/grazoprevir (EBR/GRZ) +/− RBV for 12W or 16W, and no treatment (NT). Sustained virologic response (SVR) rates were extrapolated from Phase III clinical trials and stratified by baseline NS5A resistance associated variant for EBR/GRZ. Transition probabilities and utilities were based on a literature review and consensus by a panel of hepatologists. RESULTS: Initiation of SOF/VEL in GT1 patients resulted in the best health outcomes in terms of the lowest numbers of patients with liver‐related complications compared with EBR/GRZ, LDV/SOF, and NT (Table 1). Results were consistent across patient subpopulations, including TN, pegintereron+ribavirin (PR)‐TE, PR+protease inhibitor‐TE, NC, and CC. CONCLUSIONS: Compared to EBR/GRZ and LDV/ SOF, SOF/VEL demonstrated better overall health outcomes in GT1, with reductions up to 58%, 47% and 54% in cases of decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplant (LT), respectively. Our results highlight the longer‐term benefits of treating chronic HCV with SOF/VEL versus currently available options.

Table 1. Projected health outcomes per 10,000 patients for SOF/ VEL vs. comparator regimens in HCV GT1 patients

Disclosures:

Stuart C. Gordon ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Merck, Intercept; Consulting: CVS Caremark; Grant/Research Support: Cymba Bay, Gilead, BMS, AbbVie, Intercept, Conatus, Exalenz, Merck; Speaking and Teaching: Gilead, Intercept

Douglas T. Dieterich ‐ Advisory Committees or Review Panels: Gilead, BMS, Abbvie, Janssen, Merck, Achillion

Robert Wong ‐ Advisory Committees or Review Panels: Gilead; Grant/Research Support: Gilead

Kimberly Ann Brown ‐ Advisory Committees or Review Panels: CLDF, gilead, abbvie, janssen, Merck, BMS, Janssen; Grant/Research Support: Gilead, abbvie, janssen, duke medical research, Merck; Speaking and Teaching: CLDF

Marcelo Kugelmas ‐ Advisory Committees or Review Panels: Merck, Abbvie, Janssen, Salix; Consulting: Abbvie, Merck, Gilead, Janssen; Grant/Research Support: roche, Intercept, Hologic, Gilead, Janssen, Roche, Anadys, Salix, abbvie; Speaking and Teaching: Abbvie, Gilead, Merck, Janssen, Salix

Sammy Saab ‐ Advisory Committees or Review Panels: BMS, Gilead, Merck, Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead, Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion, Johnson and Johnson, BMS, Gilead

Aijaz Ahmed ‐ Consulting: Bristol‐Myers Squibb, Gilead Sciences Inc., Roche, AbbVie, Shire, Janssen pharmaceuticals; Grant/Research Support: Gilead Sciences Inc

The following people have nothing to disclose: Zobair M. Younossi

¹Cedars‐Sinai Medical Center, Los Angeles, CA; ²University of Toronto, Toronto, ON, Canada; ³Queen Marys, University of London, London, United Kingdom; ⁴Gilead Sciences, Foster City, CA; ⁵University of California San Diego, San Diego, CA; ⁶Johns Hopkins University, Baltimore, MD; ⁷VA Pittsburgh Healthcare System, Pittsburgh, PA

BACKGROUND: Gender differences in both safety and efficacy have been reported for interferon‐based HCV treatments. Data in large cohorts of women with HCV treated with direct acting antivirals are lacking. The aim of this analysis was to evaluate the influence of gender on the efficacy and safety of the RBV‐free regimen of SOF/VEL 400/100 mg in patients with HCV genotypes (GT) 1‐6. METHODS: This secondary analysis included patients enrolled in ASTRAL 1, 2, 3, or 5, all who received SOF/VEL 400/100 mg daily for 12 weeks. Patients with decompensated liver disease (ASTRAL 4) were excluded from this analysis. In ASTRAL 5, the HIV/HCV co‐infected study, 14% of patients enrolled were women and 86% were men. Demographics, sustained virological response at 12 weeks (SVR12) and adverse events (AEs) were assessed by gender using Fisher's exact and Chi‐square tests. RESULTS: Overall, 1,141 patients were treated with SOF/VEL in the Phase III ASTRAL 1,2, 3, and 5 trials. The overall SVR12 in women was 99% and the relapse rate was <1% (3/421). In men, the overall SVR12 was 97% and the relapse rate was 2% (12/721). Demographics, SVR12, and AEs by gender are described in Table 1. Women reported higher rates nausea, headache, and nasopharyngitis than men. Further analysis of AEs in women will be done. However, treatment was generally well tolerated in women and men, and discontinuation rates were very low. CONCLUSIONS: In this pooled analysis, the once daily, single tablet regimen of SOF/VEL 400/l00 mg for 12 weeks was highly efficacious regardless of GT or gender and is a safe, RBV‐free option for women of all ages with HCV.

Table 1.

Disclosures:

Tram T Tran ‐ Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb; Consulting: Gilead, AbbVie, Janssen, merck; Grant/Research Support: Bristol Myers Squibb; Speaking and Teaching: Gilead

Jordan J. Feld ‐ Advisory Committees or Review Panels: Merck, Gilead, AbbVie, Bristol Myers Squibb; Grant/Research Support: AbbVie, Janssen, Gilead, Merck, Regulus

Graham R Foster ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS, Alnylam; Board Membership: Boehringer Ingelheim; Grant/Research Support: Roche, Chughai, Springbank; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen

Sarjita Naik ‐ Employment: Gilead Sciences

Macky Natha ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Joseph Llewellyn ‐ Employment: Gilead Sciences

Bruce Kreter ‐ Employment: Gilead Sciences; Stock Shareholder: Bristol‐Myers Squibb, Merck, Pfizer, Roche, Achillion, Celgene

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

David L. Wyles ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, AbbVie; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb, AbbVie, Tacere

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Shari S. Rogal ‐ Grant/Research Support: Gilead Sciences

The following people have nothing to disclose: Edward S. Eggleton, Jie Zhang

¹Henry Ford Hospital, Detroit, Ml; ²Stanford University Medical Center, Palo Alto, CA; ³South Denver Gastroenterology, Denver, CO; ⁴lcahn School of Medicine at Mount Sinai, New York, NY; ⁵UCLA, Los Angeles, CA; ⁶lnova Fairfax Hospital, Falls Church, VA

BACKGROUND AND AIM: The new oral single tablet regimen sofosbuvir / velpatasvir (SOF/VEL) has shown excellent efficacy and safety in patients with hepatitis C virus (HCV) genotypes (GT) 2 and 3. In particular, GT3 patients are considered difficult‐to‐treat populations with limited treatment options. A decision‐analytic Markov model evaluated health outcomes with SOF/VEL in GT2 and 3 compared with current recommended alternatives with high real‐world utilization. METHODS: The analysis modeled cohorts of 10,000 chronic HCV GT2 or GT3 patients with a mean age of 52 years from a US third‐party payer perspective over a lifetime horizon. 15% and 21% were cirrhotic (CC) and 10% and 40% were treatment‐experienced (TE) in GT2 and GT3, respectively. In GT2, SOF/VEL was compared to SOF+ribavirin (R) and no treatment (NT); in GT3, SOF/VEL was compared to SOF+daclatasvir (DCV)+/‐R and NT. Sustained virologic response (SVR) rates were based on Phase III clinical trials. Transition probabilities and utilities were based on a literature review and consensus by a panel of hepatologists. RESULTS: The SOF/VEL regimen resulted in the best health outcomes in terms of the lowest numbers of decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), and liver transplants (LT) when compared with all other comparators (Table 1). Results were consistent across patient subpopulations, including treatment naïve, pegintereron+ribavirin‐TE, SOF+R‐TE, non‐cirrhotics, and cirrhotics. CONCLUSION These results demonstrate that SOF/VEL is highly effective in HCV GT2 and GT3 patients, leading to the fewest cases of liver‐related complications vs. SOF+R and SOF+DCV. Furthermore, SOF/VEL provides a RBV‐free option for GT2 and GT3, and is the only available pan‐genotypic, all‐oral, once‐daily single tablet regimen for chronic HCV, simplifying treatment across GTs Although studies report that efficacy and adherence rates for all‐oral single tablet regimens are similar in real‐world and clinical trial settings, additional analyses are necessary to determine the impact of real‐world utilization

Table 1. Projected health outcomes per 10,000 patients for SOF/ VEL vs. comparator regimens in HCV GT2 and GT3 patients

¹ SOF+DCV is substituted where SOF+R is not recommended in TE‐SOF+R; ²Average across 12+R, 24W and 24W+R

Disclosures:

Stuart C. Gordon ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Merck, Intercept; Consulting: CVS Caremark; Grant/Research Support: Cymba Bay, Gilead, BMS, AbbVie, Intercept, Conatus, Exalenz, Merck; Speaking and Teaching: Gilead, Intercept

Aijaz Ahmed ‐ Consulting: Bristol‐Myers Squibb, Gilead Sciences Inc., Roche, AbbVie, Shire, Janssen pharmaceuticals; Grant/Research Support: Gilead Sciences Inc

Marcelo Kugelmas ‐ Advisory Committees or Review Panels: Merck, Abbvie, Janssen, Salix; Consulting: Abbvie, Merck, Gilead, Janssen; Grant/Research Support: roche, Intercept, Hologic, Gilead, Janssen, Roche, Anadys, Salix, abbvie; Speaking and Teaching: Abbvie, Gilead, Merck, Janssen, Salix

Douglas T Dieterich ‐ Advisory Committees or Review Panels: Gilead, BMS, Abbvie, Janssen, Merck, Achillion

Robert Wong ‐ Advisory Committees or Review Panels: Gilead; Grant/Research Support: Gilead

Kimberly Ann Brown ‐ Advisory Committees or Review Panels: CLDF, gilead, abbvie, janssen, Merck, BMS, Janssen; Grant/Research Support: Gilead, abbvie, janssen, duke medical research, Merck; Speaking and Teaching: CLDF Sammy Saab ‐ Advisory Committees or Review Panels: BMS, Gilead, Merck, Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead, Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion, Johnson and Johnson, BMS, Gilead

The following people have nothing to disclose: Zobair M. Younossi

¹Internal Medicine, Roger Williams Medical Center, Providence, RI; ²Internal Medicine, Boston University School of Medicine, Boston, MA; ³Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA; ⁴Medicine, University of Illinois College of Medicine, Chicago, IL; ⁵Biostatistics, Brown University School of Public Health, Providence, RI; ⁶Medicine and Surgery, UCLA, Los Angeles, CA; ⁷Transplant Hepatology, Simmons Transplant Institute, Baylor All Saints Medical Center, Fort Worth, TX; ⁸Maple Health Group, New York, NY

Background: In the era of direct‐acting antiviral therapy (DAA) for chronic hepatitis C (HCV), the decision to treat HCV liver transplant (LT) waitlist candidates has been controversial. It is thought that by treating these candidates prior to LT, their Model End‐Stage Disease (MELD) score may improve and thereby place them in a “purgatory MELD,” which would reduce their likelihood of receiving a LT. No data have been reported to determine if “purgatory MELD” does indeed exist. Methods: Using the United Network for Organ Sharing (UNOS) database, we compared HCV LT waitlist candidates 18 months before (pre‐DAA: May 2012 to October 2013) and after (post‐ DAA: January 2014 to June 2015) FDA approval of DAA agents (November to December 2013). We determined rates for transplant and death using removal codes for deceased donor transplant, death, and too sick to transplant. All statistical analyses were performed using SAS 9.4. Results: Overall there were a total of 20,411 HCV waitlist LT candidates, 10,606 candidates in pre‐DAA period and 9,805 candidates in post‐DAA period. Compared to pre‐DAA period, HCV waitlist LT candidates during the post‐DAA had a significantly lower rate of removal due to death (11.5 % to 7.4%, p < 0.01) and too sick to transplant (11.3% to 7.9 %, p < 0.01) (Table). Post‐DAA HCV waitlist LT candidates did however have a significantly lower rate of liver transplantation (38.7% to 29.9%, p < 0.01). Discussion: Although post‐DAA HCV LT waitlist candidates had a lower likelihood of receiving a transplant, their likelihood of dying on the waitlist was significantly lower Further data needs to be evaluated to determine the role of “purgatory MELD” within this population.

Table. HCV liver transplant waitlist candidate transplant and death rates, pre‐DAA versus post‐DAA.

Disclosures:

Aijaz Ahmed ‐ Consulting: Bristol‐Myers Squibb, Gilead Sciences Inc., Roche, AbbVie, Shire, Janssen pharmaceuticals; Grant/Research Support: Gilead Sciences Inc

Sammy Saab ‐ Advisory Committees or Review Panels: BMS, Gilead, Merck, Janssen; Grant/Research Support: Gilead; Speaking and Teaching: BMS, Gilead, Merck, Janssen, Salix, Onyx, Bayer, Janssen; Stock Shareholder: Achillion, Johnson and Johnson, BMS, Gilead

Stevan A Gonzalez ‐ Speaking and Teaching: Gilead, Salix, AbbVie, Merck Rachel Beckerman ‐ Consulting: Gilead Sciences

The following people have nothing to disclose: George Cholankeril, Ryan B. Perumpail, Eric R. Yoo, Menghan Hu

Hiroshima University, Hiroshima, Japan

Background We assessed risk factors for the development of hepatocellular carcinoma (HCC) following successful eradication of hepatitis C virus (HCV) with interferon therapy and direct anti‐viral agents (DAA) therapy in cohort study. Methods We retrospectively evaluated patients who achieved SVR by oral DAA interferon‐free regimens; daclatasvir/asunaprevir (DCV/ASV, n=150) and by pegylated‐interferon plus ribavirin (Peg‐IFN/RBV, n=201). In all patients, the background was chronic hepatitis or cirrhosis caused by HCV genotype 1b, received HCC surveillance by tumor markers (AFP, DCP), ultrasonography and/or dynamic computed tomography at least biannually and with no evidence of HCC development prior to HCV eradication and within a year following eradication. During the observation period (median 46 months: range 12‐160), 10 (3%) of 351 patients developed HCC after HCV eradication. After 29 months from HCV eradication to HCC development, 1 (7%) of DAA‐treated patients developed HCC The 3‐ and 5‐year cumulative HCC development rates were 5% and 0%,respectively, in the DAA group, and 7% and 13 % in the Peg‐IFN/RBV group (p=0.353), treatment regimen was not associated with development of HCC after HCV eradication As independent risk factors for HCC development, multivariate analysis identified male gender (HR, 0.12: 95%CI, 0.015‐927: P=0.047), advanced fibrosis stage (F3/4) (HR, 8.5: 95%CI, 2.0‐35.2: P=0.003) and heavy alcohol intake (HR, 4.6: 95%CI, 1.1‐18.9: P=0.003). Serum AFP level was measured before treatment, 1, and 2 years after anti‐viral treatment. We excluded from this analysis those patients who developed HCC during the follow‐up. The baseline AFP level was 16 (1‐343) ng/ml in the DAA group, which was higher than that of the Peg‐IFN/RBV group [9 (2‐87) ng/ml]. The AFP level gradually decreased in both groups after anti‐viral therapy and was similar at 1 and 2 years after the start of anti‐viral therapy (p value not significant). Conclusions We demonstrated in the present study that the rate of HCC development was reduced in patients infected with HCV genotype 1b, after achieving SVR with DAA‐based regimen The impact of DAA‐based treatment was similar to that of IFN‐based treatment with regard to HCC risk reduction in patients who achieved SVR.

Disclosures:

Michio Imamura ‐ Grant/Research Support: Bristol‐Meyers Squibb; Speaking and Teaching: Bristol‐Meyers Squibb

Kazuaki Chayama ‐ Advisory Committees or Review Panels: Mitsubishi Tanabe, Taisho Toyama; Consulting: AbbVie; Grant/Research Support: Ajinomoto, Abb‐ Vie, Aska, Asstellas, Aska, Bristol Squibb, Daiichi Sankyo, Dainippon Sumitomo, Daiichi Sankyo, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Nippon Kayaku, Otsuka, Sogo Rinsho M√©dV©fi, Taiho, Takeda, Toray, Torii, Tsumura, Zeria; Speaking and Teaching: Abbott, AbbVie, Ajinomoto, Astellas, AstraZeneca, Bayer, Bristol Squibb, Chugai, Dainippon Sumitomo, Eidia, Eisai, Gilead, GlaxoSmithKline, JIMRO, Johnson & Johnson, Mitsubishi Tanabe

The following people have nothing to disclose: Yuko Nagaoki, Hiroshi Aikata, Tomoki Kobayashi, Tomokazu Kawaoka, Masataka Tsuge, Akira Hiramatsu, Yoshiiku Kawakami

¹Hepatology, Hospital Clinic CIBERhed, Barcelona, Spain; ²Vasculitis Research Unit.Department of Autoimmune Diseases, Hospital Clinic, Barcelona, Spain; ³Laboratory of Systemic Autoimmune Diseases “Josep Font”, CELLEX, Department of Systemic Autoimmune Diseases, Hospital Clinic of Barcelona, IDIBAPS,Barcelona, Spain, Hospital Clinic, Barcelona, Spain

Background: Although current direct acting antivirals (DAAs) have taken a big step forward in HCV therapy, experience in patients with HCV‐cryoglobulinemic vasculitis (CV) is limited. Aim: To evaluate clinical and immunological outcomes in HCV‐CV subjects treated with oral DAAs 12 weeks after the end of therapy. Methods: Prospective observational study of HCV‐patients with circulating cryoglobulins who received DAAs therapy Patients were grouped in two cohorts: asymptomatic with cryoglobulins (ACC) and patients with CV (HCV‐CV). Complete immunological response (CIR) was defined by complement normalization and cryoglobulins neg‐ ativization 12 weeks after therapy (FU12). Among those with HCV‐VC, clinical remission was considered complete if BVAS v3 score=0 or all affected organs improved and partial if BVAS v3<50% of entry score. Results: 65 Caucasian patients were included, 36HCV‐CV and 29 ACC. No significant differences were observed between groups regarding age (median 61 years), viral‐genotype (83% G1b), null‐responders (50%) or antiviral therapy [3D (33%) and LDV/SOF (29%)]. Female gender was more common in HCV‐CV group (72% vs. 48%), and cirrhosis in ACC group (69%vs 47%). HCV‐CV patients showed significantly elevated rheumatoid factor (RF) (80 vs 20 IU/mL;p=0.01), lower C4 complement fraction (0.02 vs 0.06 g/L;p=0.01) and slightly higher cryoglobulins (3vs2.3 %; p=0.1) Among HCV‐CV, the most common manifestations were asthenia(70%), purpura(66%), polyneuropathy(50%), arthralgia(31%) and renal involvement(22%). Twelve patients received glucocorticoids and 2 rituximab. SVR12 rate was 92% (HCV‐CV:92% and ACC:93%). At FU12, cryoglobulins and C4 improved equally in both groups, but RF decrease was greater in HCV‐CV (‐25 vs. 0 IU, p=0.03). CIR was achieved in 42% without significant differences between groups(36% and 48%). A cryocrit >2,7%(median)at baseline was associated to non‐CIR (OR=6.7[2.2‐20.1];p=0.01). Despite the persistence of cryoglobulins and abnormal C4 in 50% of HCV‐CV patients, 29 (80%) patients achieved clinical remission (complete in 69% and partial in 11%). Median BVAS. v3 score decreased from 6 to 0 (p<0.01), with a resolution of purpura and arthralgia in 28/32 (90%) plus improvement of renal and neurological symptoms in 6/8 (75%) and 14/18 (77%), respectively. Glucocorticoid dosage could be reduced in 75% of patients Conclusions: Despite a short follow‐up, 42% of patients with HCV and circulating cryoglobulins achieved a CIR after SVR. Baseline cryocrit >2.7% was the only independent factor related to non‐immunological response However, SVR12 was associated with clinical improvement in a significant proportion of HCV‐CV patients (80%).

Disclosures:

María‐Carlota Londono ‐ Consulting: Janssen, Gilead, BMS; Speaking and Teaching: MSD, Abbvie

Xavier Forns ‐ Consulting: Jansen, Abbvie; Grant/Research Support: Jansen, Abbvie

The following people have nothing to disclose: Martin S. Bonacci, José Hernandez‐Rodríguez, Zoe Mariño, Patricia Gonzalez, José M. Sánchez‐Tapias, Manel Ramos Casal, Sabela Lens

¹nephrology, institute of liver and biliary sciences, N.Delhi, India; ²Hepatology, Institute of liver and biliary sciences, Delhi, India; ³virology, ilbs, New Delhi, India

Chronic hepatitis C virus [HCV] infection is more prevalent in patients with advanced chronic kidney disease on Hemodialysis(HD) as compared to the general population. Direct acting antiviral (DAAs) have been very effective in chronic hepatitis C However, treatment of HCV in patients with advanced CKD on HD remains a major challenge due to the lack of reported efficacy and safety data of DAAs in this population We investigated the efficacy and safety of Sofosbuvir (SOF) and Ribavirin (RBV) in chronic HCV infected CKD patients on HD. Patients and methods: Patients with CKD on HD having chronic HCV infection, were prospectively enrolled between September 2015 ‐June 2016 to receive SOF with RBV for 24 weeks Prior to starting treatment each patient was informed that the use of sofosbuvir is not commercially approved in individuals with severe renal impairment All patients consented to the off‐label use of SOF, understanding that safety and efficacy under such circumstances is unknown Patients were started on SOF 400 mg daily and RBV at 200 mg once to thrice weekly (as per tolerability of patients and serial Hb values) Treatment‐induced anaemia was managed with erythropoietin (EPO) and iron. Safety and efficacy data were collected; including SVR12 and SVR24 data for all patients after completing therapy. Results: 48 patients have been enrolled, with mean age of 42.79 ±10.98 yrs. HCV genotype 1 was present in 28(58.3%) and genotype 3 in 20 (41.7%) patients. 39% patients have completed 24 weeks of therapy The virological cure was achieved in 19/19 (100%) of patients who have completed 24 weeks. Those who have reached 12 weeks & 24 weeks post‐treatment had 100 % SVR at 12 & 24 Wk. Mean drop in haemoglobin was 1.12 g/dl. 34% patients required adjustment in ribavirin dosage and increase in erythropoietin dose 25% patients needed blood transfusion and 3 patients discontinued ribavirin due to persistent low haemoglobin Conclusions: Sofosbuvir plus ribavirin therapy, given for 24 weeks appears to be well tolerated in patients with ESRD on HD with 100% SVR at 12 weeks.

Disclosures:

The following people have nothing to disclose: Sumanlata Nayak, Manoj Sharma, Rajendra P Mathur, Prem prakash Varma, Ekta Gupta, Ashok Choudhary, Kapil D. Jamwal, Rakhi Maiwall, Guresh Kumar, Ankit Bhardwaj, Shiv K. Sarin

Gastroenterology, Komaki city hospital, Komaki, Japan

Abstract Background : Acoustic radiation force impulse (ARFI) elastography is a non‐invasive method for measuring liver stiffness However, there are no reports evaluating the value of ARFI elastography for liver fibrosis in chronic hepatitis C patients with a sustained virological response (SVR) Aims: To investigate the diagnostic performance of ARFI elastography and the effect of the duration after eradication of HCV for the liver stiffness using AFRI elastography in hepatitis C virus (HCV) infected patients with an SVR. Methods: In this prospective study, we enrolled 336 patients: 121 HCVpatients with an SVR (44.6% women) and 215 patients with HCV (47.9% women). A needle liver biopsy was performed for all patients ARFI elastography measurements of all patients were performed on the same day of liver biopsy The post‐SVR biopsy was performed 5.9 ± 1.8 years after the end of the therapy Results: The diagnostic accuracies expressed as areas under the receiver operating characteristic curves for ARFI elastography in HCV patients with an SVR and those in patients with HCV were 0.818 and 0.875 for the diagnosis of significant fibrosis (≥F2), 0.909 and 0.888 for the diagnosis of severe fibrosis (≥F3), and 0.981 and 0.890 for the diagnosis of liver cirrhosis (F4), respectively The respective mean LS values as assessed using ARFI elastography (m/s) for fibrosis stages F0‐1, F2, F3,and F4 were 1.10 ± 0.23, 1.22 ± 0.22, 1.35 ± 0.42, and 2.16 ± 0.64 in patients with SVR, and 1.23 ± 0.26, 1.55 ± 0.50, 1.90 ± 0.70, and 2.27 ± 0.58 in patients with HCV infection The mean LS values as assessed using ARFI elastography were markedly lower in patients with SVR compared with those in patients with HCV infection with regard to the same stage of fibrosis. The mean LS values as assessed using ARFI elastography were compared among patients with HCV, patients with short‐term SVR (observation period after SVR< 5.9 years), and patients with long‐term SVR (observation period after SVR ≥ 5.9 years) for each fibrosis stage. The respective mean LS values as assessed using ARFI elastography (m/s) for fibrosis stages F0‐1, F2‐3,and F4 were 1.22 ± 0.26, 1.70 ± 0.61, and 2.27 ± 0.58 in patients with HCV, 1.15 ± 0.26, 1.32 ± 0.28, and 2.12 ± 0.53 in patients with short‐term SVR, and 1.06 ± 0.20, 1.06 ± 0.22, and 2.24 ± 0.86 in patients with long‐term SVR. In patients with F0‐1, F2‐3, a significant decrease in LS values was observed according to observation period after SVR. Conclusions:The liver stiffness values were lower in patients with SVR compared with those in patients with HCV at the same stage of fibrosis. The liver stiffness values were affected by the duration after SVR.

Disclosures:

The following people have nothing to disclose: Yoshihiko Tachi

¹Intermountain Medical Center, Murray, UT; ²Weill Cornell Medical College, NewYork, NY; ³School of Medicine, University of Colorado Denver, Aurora, CO; ⁴Liver Institute of Virginia, Richmond, VA; ⁵Huntington Medical Research Institute, Pasadena, CA; ⁶Johns Hopkins University, Baltimore, MD; ⁷Gilead Sciences, Foster City, CA; ⁸Baylor University Medical Center, Dallas, TX; ⁹Beth Israel Deaconess Medical Center, Boston, MA

Introduction In the ASTRAL‐4 study, HCV infected patients with Child‐Pugh B cirrhosis achieved an SVR12 of 96% after 12 weeks of sofosbuvir/velpatasvir (SOF/VEL) and ribavirin (RBV). In contrast with other regimens evaluated in patients with decompensated cirrhosis where RBV dosing was 600 mg/day, weight based RBV dosing (1000‐1200 mg/day) was used in the ASTRAL‐4 study. This analysis compares the safety and tolerability of SOF/VEL and weight based ribavirin dosing to the safety and tolerability of ledipasvir/sofosbuvir (LDV/SOF) and RBV 600 mg as reported in the SOLAR‐1and ‐2 studies. Methods: Treatment‐emergent adverse events and laboratory abnormalities were compared between patients with CPT‐B cirrhosis (pretransplant) treated with SOF/VEL with weight‐based RBV for 12 weeks in the ASTRAL‐4 study and patients treated with LDV/SOF with 600 mg RBV for 12 weeks in the SOLAR‐1 and SOLAR‐2 studies. The tolerability of RBV was assessed by review of RBV dose modification, dose reductions and discontinuations. Results: Patients treated with SOF/VEL and weight‐ based RBV had a lower incidence of adverse events (90.8%) compared with patients treated with LDV/SOF and 600 mg RBV (96.6%). However for both regimens most adverse events were mild or moderate in severity and only one patient treated with SOF/VEL with weight‐based RBV and one patient treated with LDV/SOF with 600mg RBV had a treatment related serious adverse event. Three patients who received SOF/VEL and weight‐based RBV died and one patient who received LDV/SOF with 600mg RBV died; no deaths were assessed as treatment related. Table 1 presents a summary of postbaseline hemoglobin and RBV dose modifications. There was a higher incidence of RBV dose reductions, interruptions and modifications among patients treated with SOF/VEL and weight based RBV compared with patients treated LDV/SOF and 600mg RBV. Conclusions The higher incidence of hemoglobin reductions in HCV infected patients with CPT‐B cirrhosis treated with SOF/VEL with weight based RBV compared with patients treated with LDV/SOF with 600 mg RBV was managed with more frequent dose modification of RBV without discontinuation of treatment. This group of patients should be treated by providers experienced in the care of patients with advanced liver disease and the management of RBV associated toxicities.

Disclosures:

Michael R. Charlton ‐ Consulting: Gilead Sciences; Grant/Research Support: GIlead Sciences, Merck, Janssen, AbbVie, Novartis, Intercept

Robert S. Brown ‐ Advisory Committees or Review Panels: Vital Therapies; Consulting: Gilead, Janssen, Abbvie, Merck, BMS

Gregory T. Everson ‐ Advisory Committees or Review Panels: Roche/Genentech, Abbvie, Galectin, Bristol‐Myers Squibb, HepC Connection, BioTest, Gilead, Merck; Board Membership: HepQuant LLC, PSC Partners, HepQuant LLC; Consulting: Abbvie, BMS, Gilead, Bristol‐Myers Squibb; Grant/Research Support: Roche/Genentech, Abbvie, Bristol‐Myers Squibb, Merck, PSC Partners, Gilead; Management Position: HepQuant LLC, HepQuant LLC; Patent Held/Filed: Univ of Colorado; Speaking and Teaching: Abbvie

Mitchell L. Shiffman ‐ Advisory Committees or Review Panels: Merck, Gilead, Bristol‐Myers‐Squibb, Abbvie; Grant/Research Support: conatus, Immuron, Merck, Gilead, Galactin, Bristol‐Myers‐Squibb, Abbvie, Beckman‐Coulter, NGMBio, Intercept, Novartis, Eisai, Shire; Speaking and Teaching: Merck, Gilead, Bristol‐Myers‐Squibb, Abbvie, Intercept

Myron J. Tong ‐ Speaking and Teaching: BMS, Gilead, Genentech

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Di An ‐ Employment: Gilead Sciences, Inc

Anu O. Osinusi ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

John McNally ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Jacqueline G. O'Leary ‐ Advisory Committees or Review Panels: Gilead, Intercept, Novartis; Consulting: Abbvie, Fish & Richarson PC; Grant/Research Support: Fisher Scientific; Speaking and Teaching: Gilead, Abbvie, Merck, Astellas; Stock Shareholder: Medfusion

Michael P. Curry ‐ Consulting: Alexion, Bristol Meyers Squib, Abbvie; Grant/ Research Support: Gilead Sciences, Conatus

The following people have nothing to disclose: Lingling Han, Mani Subramanian

¹Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, United Kingdom; ²AbbVie Inc., North Chicago, IL; ³Second University of Naples, Naples, Italy; ⁴University of Calgary, Alberta, AB, Canada; ⁵Carol Davila University of Medicine and Pharmacy, National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania; ⁶Charité Universtots‐ medizin Berlin, Berlin, Germany; ⁷University Hospital of Malaga, IBIMA, CIBERehd, Andalusia, Spain; ⁸Centro de Investifaciàn Farmaceutica Especializada s.ç, Jalisco, Mexico; ⁹Westmead Hospital, Westmead Institute for Medical Research, Westmead, Sydney, NSW, Australia; ¹⁰Central Scientific Research Institute for Gastroenterology, Moscow, Russian Federation; ¹¹Hospital Santa Maria, Medical School of Lisbon, Lisbon, Portugal; ¹²Department of Infectious Diseases, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey; ¹³Institut National de la Santé et de la Recherche Médicale, Paris, France; ¹⁴University of Sydney, Sydney, NSW, Australia

Introduction: In phase 3 trials, the 3 direct‐acting antiviral (3‐DAA) regimen of ombitasvir/paritaprevir/ritonavir (parita‐ previr identified by AbbVie and Enanta) and dasabuvir ± ribavirin (RBV) achieved high sustained virologie (SVR) rates with a favorable safety profile in >2300 HCV patients, including those with compensated cirrhosis. TOPAZ‐I evaluates the impact of SVR12 on long‐term progression of liver disease over 5 years' post‐treatment (PT) follow‐up in patients with chronic HCV GT1 infection receiving 3‐DAA ± RBV. Methods: TOPAZ‐I is an on‐going phase 3b, international, multicenter, open label study which enrolled HCV GTl‐infected treatment‐naive or interferon‐experienced patients without cirrhosis or with compensated cirrhosis across 187 centers in 27 countries. Patients were to receive 3‐DAA ± RBV for 12 or 24 weeks, based on subtype and cirrhosis status, as consistent with the approved local labels. First interim results include SVR12 (HCV RNA < LLOQ 12 weeks PT), safety and clinical outcomes Change in liver fibrosis from baseline was evaluated by FibroScan®. Results: 1564 patients received study drug (50% male; 97% White, 15% compensated cirrhosis). 79% (1228/1564) of patients reached SVR12 time point. ITT SVR12 was achieved in 97% (1190/1228) of patients who reached PTW12; 95% and 97% in patients with and without cirrhosis, respectively In patients who achieved SVR12, mean FibroScan® scores improved over time, with greatest improvements seen in patients with cirrhosis (mean kPa change from baseline to PTW12: F0‐F1 = −0.55, F2 = −1.64, F3 = −2.75, F4 = −6.45). In total, 66% (1024/1564) patients experienced an AE, with fatigue (18%), headache (17%), nausea (11%), pruritus (11%), and insomnia (11%) occurring in >10% of patients. The majority of AEs were mild/moderate in severity, 37 (2%) patients experienced serious AEs, 6 (0.4%) patients discontinued study drug due to AEs. Grade 3‐4 laboratory abnormalities were rare. Clinical outcomes are reported in the table Conclusions: Data from this large study confirm the efficacy and safety results observed in registrational trials of 3‐DAA ± RBV in HCV GT1‐infected patients Preliminary data show a beneficial impact on liver fibrosis; clinical outcomes were infrequent. Updated safety, efficacy and clinical outcomes will be presented.

*n=l pneumonia leading to hepatic decompensation and multiple organ failure; n=l ischemic heart disease

†includes ascites, variceal bleeding, or hepatic encephalopathy

Disclosures:

Kosh Agarwal ‐ Advisory Committees or Review Panels: Gilead, BMS, Novartis, Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead, BMS, GSK

Emily O. Dumas ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Giovanni B. Gaeta ‐ Advisory Committees or Review Panels: Janssen, Merck, Abbvie, Roche; Speaking and Teaching: BMS, Gilead, merck

Sam Lee ‐ Employment

Eckart Schott ‐ Advisory Committees or Review Panels: Gilead, Roche, Bayer, BMS, Abbvie, Janssen, MSD; Speaking and Teaching: Gilead, Novartis, Roche, MSD, Bayer, Falk, BMS, Janssen, Abbvie

Alma M. Perez ‐ Advisory Committees or Review Panels: GILEAD, LA ROCHE, ABBVIE, MSD; Grant/Research Support: JANSSEN; Speaking and Teaching: GILEAD, LA ROCHE, ABBVIE, JANSSEN, BMS, MSD

Jacob George ‐ Advisory Committees or Review Panels: Pharmaxis, BMS, MSD, Gilead, Janssen, Abbvie; Grant/Research Support: MSD

Rui T. Marinho ‐ Advisory Committees or Review Panels: Abbvie, MSD, BMS, Janssen, Bayer

Mariem Charafeddine ‐ Employment: AbbVie Ltd; Stock Shareholder: AbbVie Ltd Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott Kevin Howieson ‐ Employment: AbbVie

Daniel E. Cohen ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Fabien Zoulim ‐ Advisory Committees or Review Panels: Janssen, Gilead, Novira, Abbvie, Arbutus, Transgene; Consulting: Roche; Grant/Research Support: Novartis, Gilead, Scynexis, Roche, Novira, Assemblypharm, Janssen; Speaking and Teaching: Bristol Myers Squibb, Gilead

The following people have nothing to disclose: Adrian Streinu‐Cercel, Raul J. Andrade, Igor G. Bakulin, Resat Ozaras, Li Liu, Melannie Co

AbbVie Inc., North Chicago, IL

Background: An HCV regimen containing ombitasvir (NS5A inhibitor) and paritaprevir (NS3 protease inhibitor identified by AbbVie and Enanta) with ritonavir [OBV/PTV/r] plus ribavirin (RBV) is highly efficacious for the treatment of HCV genotype (GT) 4 infection. We utilized a large dataset of NS5A sequences containing diverse HCV GT4 subtypes isolated from patients treated with OBV/PTV/r ± RBV to assess genetic diversity by geographic region, analyze patient demographics and baseline sequence variability across GT4 subtypes, and report the development of viral resistance in virologic failure (VF) patients. Methods: The full‐length NS5A gene was sequenced by population or next‐generation sequencing (NGS) from the baseline samples of 132 non‐cirrhotic (PEARL‐I) or 118 cirrhotic (AGATE‐1) GT4‐infected patients. NS5A sequences were included in a phylogenetic analysis to assess genetic relationships among and within GT4 subtypes by country. The prevalence of baseline polymorphisms and treatment‐emergent resistance‐associated variants (RAVs) in NS5A were analyzed. Results: Sixteen GT4 subtypes were identified in the combined dataset (4a, 4b, 4c, 4d, 4e, 4f, 4h, 4k, 4l, 4n, 4o, 4p, 4q, 4r, 4t, 4). Subtype prevalence varied by country of enrollment, and in study AGATE‐1 the subtype prevalence by country of origin was closely associated with the reported distribution of GT4 subtypes in Africa, Europe, and North America. A phylogenetic analysis of NS5A sequences revealed two sequence clusters within subtype 4a which correlated with the country of origin for each sample; one cluster contained sequences from Egypt and the Middle East, while the second cluster contained sequences originating from Europe. Baseline demographics analyses also revealed that the distribution of patient race was significantly different across GT4 subtypes 4a, 4d, and non‐ 4a/4d. Baseline amino acid variability in NS5A was frequently detected across GT4 subtypes but had no impact on treatment outcome. Overall 5 out of 255 patients experienced VF, of which 1 was infected with GT4a and 4 were infected with GT4d, and the predominant RAVs at the time of failure were D168V in NS3/4A and L28I/S/V or Y93H in NS5A. Conclusions: Overall, high response rates were observed among patients infected with 16 HCV GT4 subtypes with no impact of NS5A baseline polymorphisms on treatment outcome. GT4 subtype distribution differed based on patient demographics and geography Two phylogenetic clusters within subtype 4a were found to segregate by country of origin and suggest a genetically distinct strain of 4a circulating in Egypt versus Europe

Disclosures:

Gretja Schnell ‐ Employment: AbbVie Inc. ; Stock Shareholder: AbbVie Inc.

Rakesh Tripathi ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Jill Beyer ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Thomas Reisch ‐ Employment: Abbvie; Stock Shareholder: Abbvie

Coleen Hall ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Yao Yu ‐ Employment: Abbvie

Niloufar Mobashery ‐ Employment: Abbvie; Stock Shareholder: abbvie

Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott

Christine Collins ‐ Employment: AbbVie

Gilead Sciences, Inc, Foster City, CA; ²AP‐HP Hôpital Beajon, Clichy, France; ³Monash Medical Center, Clayton, VIC, Australia; ⁴Schiff Center for Liver Disease, University of Miami, Miami, FL; ⁵Gastroenterology, IRCCS Maggiore Hospital University of Milan, Milan, Italy

Background: The major metabolite of sofosbuvir (SOF), GS‐331007, is cleared renally and accumulates in severe renal impairment or end stage renal disease Although these populations were excluded from most Phase 2 and 3 clinical trials, patients with mild and moderate renal impairment were enrolled This retrospective analysis presents the safety profile of SOF‐based therapies in these groups Methods: Safety data from patients with or without compensated cirrhosis enrolled in 48 Phase 2 or 3 studies of SOF+RBV, LDV/SOF±RBV, and SOF/VEL±RBV were assessed according to +/‐RBV and degree of renal impairment: normal renal function (estimated glomerular filtration rate [eGFR; using the Cockcroft‐Gault equation] >80 ml/min), mild renal impairment (eGFR 50‐80 mL/min), or moderate renal impairment (eGFR 30‐49 mL/min). Results: 11,111 patients were included in this analysis; 2,186 (20%) had mild or moderate renal impairment at baseline Mean eGFR was 119, 69, and 44 mL/min for patients with normal renal function (n=8925), mild (n=2043), or moderate (n=143) renal impairment, respectively. Baseline characteristics were generally similar across groups, except patients with impaired renal function were older. Table 1 provides a summary of adverse events (AEs). Patients receiving RBV had higher rates of Grade 3‐4 AEs, SAEs, and discontinuations as compared to patients not receiving RBV; this difference was more pronounced among those with renal impairment Among patients not receiving RBV, there were similar rates of Grade 3‐4 AEs and discontinuations due to AE across groups. Patients with moderate renal impairment had higher rates of SAEs but most were not treatment‐related. Conclusions: Treatment with SOF‐based regimens was well‐tolerated in patients with mild or moderate renal impairment. Differences were seen in RBV tolerability between patients with moderate renal impairment, compared to those with no or mild renal impairment.

Overall Summary of Safety in Patients Treated with a SOF‐con‐ taining Regimen According to Renal Function and the Presence of RBV

Disclosures:

Francois Durand ‐ Advisory Committees or Review Panels: Astellas, Novartis, BMS; Speaking and Teaching: Gilead

Stephen Pianko ‐ Advisory Committees or Review Panels: Roche, Novartis, GILEAD, Roche, Novartis; Consulting: GILEAD; Speaking and Teaching: JANSSEN, BMS

Shampa De‐Oertel ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

John McNally ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

John G. McHutchison ‐ Employment: gilead; Stock Shareholder: gilead

Eugene R. Schiff ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, Janssen, Salix Pharmaceutical, Pfizer, Arrowhead, Astrazeneca, CVS; Consulting: Acorda; Grant/Research Support: Bristol Myers Squibb, ABBVIE, Gilead, Merck, Conatus, Medmira, Roche Molecular, Janssen, Orasure Technologies, Discovery Life Sciences, Siemens, Beckman Coulter, Siemens, Ortho JNH, Intercept, Beckman

Massimo Colombo ‐ Advisory Committees or Review Panels: Gilead Sciences, Abbvie, BMS, Bayer, Merck; Speaking and Teaching: Gilead Sciences, Abbvie, BMS, Bayer, Merck, Janssen, Sanofi, Vertex

The following people have nothing to disclose: Liyun Ni

¹ University of North Carolina at Chapel Hill, Chapel Hill, NC; ²School of Medicine, Yale, New Haven, CT; ³Medicine, University of Florida, Gainesville, FL; ⁴Hepatology, University of Pennsylvania, Philadelphia, PA; ⁵Liver Institute of Virginia, Bon Secours, Richmond, VA; ⁶Medicine, Goethe University Hospital, Frankfurt, Germany; ⁷Medicine, University of California San Diego, San Diego, CA; ⁸Medicine, University of California, San Francisco, San Francisco, CA; ⁹Medicine, Liver Disease Center Scripps Clinic, La Jolla, CA; ¹⁰Medicine, Baylor, Dallas, TX; ¹¹Medicine, Johns Hopkins, Baltimore, MD; ¹²Medicine, Hannover Medical School, Hannover, Germany

DAAs have an outstanding safety profile in phase III trials. Post‐marketing surveillance has generated additional safety warnings about drug interactions and restricted use in decompensated cirrhosis. Aim: To evaluate detailed safety data across a broad spectrum of patients treated with DAAs in usual clinical practice. Methods: Patients enrolled in HCV‐TARGET were treated according to regional standards of care at academic (n=38) and community medical centers (n=13) in North America (n=47) and Europe (n=4). Detailed information on demographics, clinical course, and adverse events (AEs) was abstracted from medical records into a centralized data core. Data monitors systematically reviewed data for accuracy. Results: From Jan 2014 to May 2016, 5590 patients (pts) were treated with oral DAAs including 2483 (44%) pts with cirrhosis of whom 1145 (46.1%) had evidence of prior hepatic decompensation. Regimens included SOF+RBV (n=782), SOF+SMV+/‐ RBV (n=1213), LDV/SOF+/‐RBV (n=2542), PrOD+/‐RBV (n=656), PrO+/‐RBV (n=13) and SOF+DCV+/‐RBV (n=384). Therapy was completed in 4971 (89%) Early discontinuation due to AEs occurred in 101 (1.8%), and was higher among RBV‐con‐ taining vs RBV‐free regimens (55/2097, 2.6%) vs (46/3493, 1.3%). Deaths were reported in 39 pts from a variety of causes. An increase in bilirubin of ≥ 3mg/dl over baseline (bilirubin,,) occurred in 110/4678 (2.4%) pts with evaluable data, of whom 25 (22.7%) prematurely discontinued treatment Severe bilirubin_Δ5 (≥5mg/dl above baseline) occurred in 48 pts, of whom only 3 (6.3%) had concomitant ALT elevation, and 9 (18.8%) died. 32 pts had bilirubin_Δ3 associated with biliary tract disease, sepsis, or transplantation In multivariable logistic analyses excluding those patients, cirrhosis, prior hepatic decompensation, low albumin, and higher baseline bilirubin were associated with bilirubin_Δ during treatment. De novo hepatic decompensation occurred in 41/1338 (3.1%) previously compensated cirrhotic pts whereas secondary decompensating events among those with a prior history of decompensation was higher (198/1145, 17.3%). Ribavirin use was associated with secondary hepatic decompensation in the latter group, (OR 2.82, 95% CI 1.96‐4.12, p<0.01). Conclusions: The event rate for hyperbilirubinemia and decompensation was low, even among patients with advanced cirrhosis, and infrequently led to premature discontinuation of therapy. Features of advanced cirrhosis were associated with increased risk for AEs Of note, ribavirin independently increases risk of hepatic decompensation Severe hyperbilirubinemia and clinical sequelae usually occur in the absence of ALT elevations and deserve further scrutiny

Disclosures:

Michael W. Fried ‐ Consulting: Merck, Abbvie, Janssen, Bristol Myers Squibb, Gilead; Grant/Research Support: Merck, AbbVie, Janssen, Bristol Myers Squibb, Gilead; Stock Shareholder: TARGET PharmaSolutions

K. Rajender Reddy ‐ Advisory Committees or Review Panels: Merck, Janssen, BMS, Abbvie, Gilead; Grant/Research Support: Merck, BMS, Gilead, Janssen, Abbvie

Mitchell L. Shiffman ‐ Advisory Committees or Review Panels: Merck, Gilead, Bristol‐Myers‐Squibb, Abbvie; Grant/Research Support: conatus, Immuron, Merck, Gilead, Galactin, Bristol‐Myers‐Squibb, Abbvie, Beckman‐Coulter, NGMBio, Intercept, Novartis, Eisai, Shire; Speaking and Teaching: Merck, Gilead, Bristol‐Myers‐Squibb, Abbvie, Intercept

Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

Norah Terrault ‐ Advisory Committees or Review Panels: Eisai, Biotest; Consulting: BMS, Merck, Achillion, CoCrystal; Grant/Research Support: Eisai, Biotest, Vertex, Gilead, AbbVie, Novartis, Merck

Paul J. Pockros ‐ Advisory Committees or Review Panels: Janssen, Merck, BMS, Gilead, AbbVie; Consulting: Lumena, Beckman Coulter; Grant/Research Support: Intercept, Janssen, BMS, Gilead, Lumena, Beckman Coulter, AbbVie, RMS, Merck; Speaking and Teaching: AbbVie, Janssen, Gilead

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Michael P. Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

Jacqueline G. O'Leary ‐ Advisory Committees or Review Panels: Gilead, Intercept, Novartis; Consulting: Abbvie, Fish & Richarson PC; Grant/Research Support: Fisher Scientific; Speaking and Teaching: Gilead, Abbvie, Merck, Astellas; Stock Shareholder: Medfusion

David R. Nelson ‐ Grant/Research Support: Abbvie, BMS, Gilead, Merck, Janssen

Joseph K. Lim ‐ Consulting: Bristol Myers Squibb, Gilead; Grant/Research Support: Bristol Myers Squibb, Gilead

The following people have nothing to disclose: Alexander Kuo, Lucy Akushevich, Monika Vainorius

¹Rush University Medical Center, Chicago, IL; ²Merck & Co., Inc., Kenilworth, NJ

Background: It is estimated that up to one‐third of hepatitis‐C virus (HCV)‐infected patients use proton pump inhibitors (PPIs) and other acid reducing agents. Concomitant PPI use with some NS5A inhibitors impacts the pharmacokinetics (PK) of direct‐acting antiviral agents (DAAs), potentially reducing efficacy Phase I study results demonstrated no effect of PPI use on the PK of the fixed‐dose combination of elbasvir/grazoprevir (EBR/GZR) in healthy volunteers. This post hoc analysis of studies in the Phase 3 clinical program of EBR/GZR assessed the 12‐week sustained viral response (SVR12) in subjects with self‐reported PPI use and the PK of EBR/GZR in these patients. Methods: Data were derived from six Phase 3 EBR/GZR trials with treatment‐naïve or treatment experienced GT1/4‐infected subjects, with or without cirrhosis Analyses were done in the modified Full Analysis Set population (excludes administrative discontinuations). Self‐reported baseline PPI use was defined as ≥7 consecutive days of use between Day ‐7 and Day 7. Bivariate analyses assessed PPI use and other factors associated with SVR, with gender, age (continuous and dichotomous), cirrhosis status, prior treatment status, baseline HCV RNA (continuous and dichotomous), HCV genotype, and baseline resistance associated variants as variables in the models. Results: Overall, 12% (162/1322) of EBR/GZR‐treated subjects reported baseline use of PPIs. Of those, 155/162 (96%) achieved SVR12. In patients without PPI use, 1129/1160 (97%) achieved SVR12. PPI use was not a predictive factor in achieving SVR12 based on a univariate analysis (p = 0.188). In the bivariate models, none of the interaction terms was statistically significant, indicating that any potential effects of PPI were consistent across the factors considered. In addition, PPI usage was not a statistically significant effect, regardless of adjustment for the factors considered. From 3 of the 6 studies for which population PK data were available, the estimated AUC and Cmax values for EBR were comparable among patients with and without reported PPI use (table). Conclusions: These results demonstrate that PPIs use with EBR/GZR has no clinically significant effect on SVR12 rates in GT1/4‐infected patients with and without cirrhosis.

AUC=area under the curve; GM=geometric mean

*Estimated using population PK modeling

Disclosures:

Nancy Reau ‐ Advisory Committees or Review Panels: Jannsen, Merck, AbbVie, Intercept, Salix, BMS, Gilead; Grant/Research Support: Gilead, Intercept, Abb‐ Vie

Michael Robertson ‐ Employment: Merck; Stock Shareholder: Merck

Hwa‐Ping Feng ‐ Employment: Merck

Luzelena Caro ‐ Employment: Merck & Co., Inc.

Wendy W. Yeh ‐ Employment: Merck Bach‐Yen T. Nguyen ‐ Employment: Merck Janice Wahl ‐ Employment: Merck & Co,

Eliav Barr ‐ Employment: Merck; Stock Shareholder: Merck

Peggy Hwang ‐ Employment: Merck, Merck

Stephanie O. Klopfer ‐ Employment: Merck & Co., Inc.

¹Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; ²Liver Research Project Center, Hiroshima University, Hiroshima, Japan; ³PhoenixBio Co., Ltd., Higashihiroshima, Japan

Background: Although treatment‐emergent NS3/4A protease inhibitor (PI)‐resistant variants typically decrease in frequency after cessation of PI therapy in chronic hepatitis C patients, susceptibility to PIs in patients who have previously failed to respond to PI therapy has not been addressed. Methods: A total of 406 genotype 1 chronic hepatitis C patients who had detectable drug resistant‐associated variants (RAVs) in neither HCV NS5A‐L31 nor ‐Y93 prior to the treatment as determined by Invader assay were treated with daclatasvir plus asuna‐ previr. Human hepatocyte chimeric mice were injected with serum samples obtained either from treatment‐naïve patients or daclatasvir plus asunaprevir non‐responders, then treated withsimeprevir and sofosbuvir or telaprevir. The nucleotide and amino acid sequences of resistance‐associated regions of NS3 and NS5A were determined by deep sequencing. Results: Sustained virological response (SVR) was achieved in 95.0% (377 out of 397) of DAA treatment‐naYve patients, whereas in only 33.3% (3 out of 9) of patients who experienced simeprevir plus PEG‐IFN/RBV treatment failure (P = 0.0001). Multivariate logistic regression analysis identified history of simeprevir treatment (odds ratio, 56.6 for absence; P<0.001) as an independent predictor for SVR. After viral breakthrough with daclatasvir and asunaprevir treatment, NS5A‐L31/Y93 RAVs persisted at high frequencies In contrast, deep sequencing analysis showed that the frequency of NS3‐D168 RAVs gradually decreased and were completely replaced by wild‐type after cessation of therapy. Mice injected with serum from a DAA‐naïve patient or the daclatasvir plus asunaprevir non‐responder were treated with simeprevir alone or sofosbuvir in combination with either simeprevir or telaprevir. Both simperevir alone and simperevir plus sofosbuvir treatments resulted in a rapid emergence of the NS3‐D168 mutation at significantly higher frequencies in mice injected with serum from the daclatasvir and asunaprevir non‐responder compared to mice injected with serum from the DAA naïve patient. In contrast to sofosbuvir plus simeprevir treatment, sofosbuvir plus telaprevir treatment reduced serum HCV RNA levels sustainably, and emergence of NS3‐D168 RAVs was suppressed in mice injected with serum from the daclatasvir and asunaprevir non‐responder. Conclusions: Virological response to daclatasvir plus asunaprevir treatment was low in patients with simeprevir plus PEG‐IFN/RBV treatment failure. PI resistance remains even after disappearance of mutant strains by ultra‐deep sequencing. DAA combination therapy without NS3/4A PIs is recommended for patients who failed NS3/4A PI treatment.

Disclosures:

Michio Imamura ‐ Grant/Research Support: Bristol‐Meyers Squibb; Speaking and Teaching: Bristol‐Meyers Squibb

Yuji Ishida ‐ Employment: PhoenixBio Co., Ltd.

Chise Tateno ‐ Board Membership: PhoenixBio Co., Ltd.

Kazuaki Chayama ‐ Advisory Committees or Review Panels: Mitsubishi Tanabe, Taisho Toyama; Consulting: AbbVie; Grant/Research Support: Ajinomoto, AbbVie, Aska, Asstellas, Aska, Bristol Squibb, Daiichi Sankyo, Dainippon Sumitomo, Daiichi Sankyo, Eisai, GlaxoSmithKline, Mitsubishi Tanabe, Nippon Kayaku, Otsuka, Sogo Rinsho MV©dV©fi, Taiho, Takeda, Toray, Torii, Tsumura, Zeria; Speaking and Teaching: Abbott, AbbVie, Ajinomoto, Astellas, AstraZeneca, Bayer, Bristol Squibb, Chugai, Dainippon Sumitomo, Eidia, Eisai, Gilead, GlaxoSmithKline, JIMRO, Johnson & Johnson, Mitsubishi Tanabe

The following people have nothing to disclose: Hiromi Kan, Nobuhiko Hiraga, C. Nelson Hayes, Takuro Uchida, Eisuke Miyaki, Masataka Tsuge, Hiromi Abe‐Chayama, Hiroshi Aikata, Daiki Miki, Hidenori Ochi

¹UNSW Australia, Sydney, NSW, Australia; ²Yale University, New Haven, CT; ³Albert Einstein/Montefiore Medical Center, Bronx, NY; ⁴Akershus University, Oslo, Norway; ⁵Aukland City Hospital, Aukland, New Zealand; ⁶Liver Unit, Department of Gastroenterology, Tel‐Aviv Medical Center and Tel‐Aviv University, Tel‐Aviv, Israel; ⁷University of California, San Francisco, CA; ⁸IP Care, Hillsboro, NJ; ⁹China Medical University Hospital, Taichung, Taiwan; ¹⁰Vancouver Infectious Diseases Centre, Vancouver, BC, Canada; ¹¹St. Vincent's Hospital, Melborne, VIC, Australia; ¹²Merck & Co., Inc., Kenilworth, NJ

Background/Purpose: High rates of efficacy were observed in Co‐STAR, a Phase 3 trial of 12 weeks of elbasvir/grazoprevir (EBR; HCV NS5A inhibitor) / GZR; HCV NS3/4A protease inhibitor) in patients on opioid agonist therapy (OAT). HCV reinfection was observed in 6/296 (2%) of patients between the end of treatment (EOT) and follow‐up week 24. The aim of the Co‐STAR Three Year Follow‐up Study (3YFU) is to evaluate HCV reinfection and injecting risk behaviors in patients treated with EBR/GZR. Methods: This 3 year observational cohort study enrolled patients who received at least one dose of EBR/ GZR in the Phase 3 trial. Every 6 months, patients are tested for HCV RNA and if detected, viral genotype and sequencing are performed. Patients complete a questionnaire to assess drug use. Results: Of 296 patients treated in Co‐STAR, 185 patients (63%) were enrolled in the 3YFU. Patients who enrolled in the 3YFU were generally representative of the parent trial: average age, 49 years; males, 76%, white race, 79%; GT1a, 73%; GT1b, 19%; GT4, 7%; GT6, 1%. Sixty percent and 58% of patients in the 3YFU study and the Phase 3 trial had a positive urine drug screen (UDS) result at enrollment, respectively. The median time from EOT to the first visit during the 3YFU was 330 days (range: 206‐485). In addition to the 6 reinfections observed between EOT and follow‐up week 24, two viral recurrences were identified at the first visit in the 3YFU. One patient had GT1a at baseline: the patient reported non‐injection drug use (intranasal cocaine, inhaled amphetamines, inhaled cannabinoids) at follow‐up, GT3 was identified, and opiates and cannabinoids were detected by UDS. One patient had GT1b at baseline, had HCV RNA (258 lU/mL) detected at the first visit; however, the genotype was unable to be determined due to low viral load, no drug use was reported by the patient for the previous 6 months, and no drugs besides OAT were detected by UDS; this patient is not considered a reinfection while additional follow‐up is pending. Of the 185 patients in the 3YFU, 108 (58%) reported any drug use (non‐injecting or injecting) in the past 6 months Injecting drug use in the past 6 months was reported by 47 (25%) patients Among those reporting injecting drug use in the past 6 months (n=47 patients), injected drugs included heroin (n=34; 72%), amphetamines (n=8; 17%), cocaine (n=7; 15%), and other opioids (n=7; 15%). Conclusion: HCV reinfection among patients on opioid agonist therapy following elbasvir/grazoprevir treatment is uncommon despite ongoing drug use. Additional follow‐up is ongoing.

Disclosures:

Gregory Dore ‐ Board Membership: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Grant/Research Support: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Gilead, Merck, Abbvie, Bristol‐Myers Squibb

Jason Grebely ‐ Advisory Committees or Review Panels: Merck, Gilead; Grant/ Research Support: Merck, Gilead, Abbvie, BMS

Frederick Altice ‐ Grant/Research Support: Gileaad, NIH, NIDA, SAMHSA, HRSA; Speaking and Teaching: Merck, Bristol Myers Squibb, Gilead, Rush Practice Point Communications

Alain H. Litwin ‐ Advisory Committees or Review Panels: Merck, Gilead, BMS, Janssen; Grant/Research Support: Merck, Gilead

Olav Dalgard ‐ Advisory Committees or Review Panels: MSD, Janssen Cilag, Medivir, Gilead, Abbvie; Grant/Research Support: MSD, Medivir, Gilead, Abbvie

Edward J. Gane ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead Sciences, Achillion, Merck; Speaking and Teaching: AbbVie, Gilead Sciences, Merck, Alnylam

Anne Luetkemeyer ‐ Grant/Research Support: Gilead, Abbvie, Bristol Myers Squibb, Merck

Ronald Nahass ‐ Advisory Committees or Review Panels: Gilead, Merck, Janssen, BMS; Grant/Research Support: Gilead, Merck, Janssen, BMS Cheng‐Yuan Peng ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, MSD, Roche

Brian Conway ‐ Advisory Committees or Review Panels: AbbVie, Gilead, Merck; Grant/Research Support: AbbVie, Gilead, Merck, Pendopharm, Jannsen; Speaking and Teaching: AbbVie, Gilead, Merck

David M. Iser ‐ Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck, Roche

Hsueh‐cheng Huang ‐ Employment: Merck; Stock Shareholder: Merck

Isaias N. Gendrano ‐ Employment: Merck Sharp & Dohme Corp; Stock Shareholder: Merck Sharp & Dohme Corp

Peggy Hwang ‐ Employment: Merck, Merck

Michael Robertson ‐ Employment: Merck; Stock Shareholder: Merck Janice Wahl ‐ Employment: Merck & Co,

Eliav Barr ‐ Employment: Merck; Stock Shareholder: Merck Heather L. Platt ‐ Employment: Merck

The following people have nothing to disclose: Oren Shibolet, Michelle M. Kelly

¹Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; ²Associate Professor of Medicine and Surgery, Mercer University School of Medicine, Macon, GA; ³Digestive Disease Associates, Baltimore, MD; ⁴Piedmont Healthcare/Carolinas Center for Liver Disease, Statesville, NC; ⁵Division of Gastroenterology/Hepatology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI; ⁶Anne Arundel Medical Center, Digestive Disorders Associates, Annapolis, MD; ⁷Principal Investigator, Regional Clinical Research Inc., Endwell, NY; ⁸Hofstra Northwell School of Medicine, Manhasset, NY; ⁹AbbVie Inc., North Chicago, IL; ¹⁰AbbVie Deutschland GmbH&Co KG, Ludwigshafen, Germany; ¹¹Department of Medicine, University of Florida, Gainesvillle, FL; ¹²Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA

BACKGROUND: Ribavirin (RBV) is a component of guide‐ lines‐recommended treatment regimens for certain patient populations with hepatitis C virus (HCV) infection, and is known to cause decreases in hemoglobin and/or elevations of indirect bilirubin.RBV is typically administered at a weight‐based daily dosage of 1000‐1200 mg. In this study, we investigated the safety and efficacy of the direct‐acting antiviral agents (DAAs) ombitasvir/paritaprevir (identified by AbbVie and Enanta)/ ritonavir (OBV/PTV/r) plus dasabuvir (DSV) with a fixed low dose of RBV in patients with genotype 1a (GT1a) chronic HCV infection without cirrhosis. METHODS: GEODE‐II is a Phase 3, open‐label, multi‐center study designed to evaluate the safety and efficacy of OBV/PTV/r+DSV co‐administered with low‐ dose RBV (600 mg QD) for 12 weeks in GT1a HCV‐infected patients without cirrhosis, who are either HCV treatment‐naïve (TN) or treatment‐experienced (TE) to previous interferon (IFN) or pegylated IFN ± RBV therapy. Efficacy is assessed by sustained virologic response at post‐treatment week 12 (SVR12) compared with historic SVR12 rates for the same regimen coadministered with weight based RBV. Safety is assessed in all patients receiving at least 1 dose of study drugs Results will be presented for the intent‐to‐treat (ITT) and modified (m) ITT (excluding discontinuations due to non‐viral failures and non‐drug related AEs) populations. RESULTS: A total of 105 patients (52% female, 86% white) were enrolled in this study, of whom 89% were TN. As of the data cut‐off date (May 11, 2016) 79 patients reached the end of treatment. The SVR4 rate was 94% for the 71 ITT patients who reached post‐treatment week 4 AEs were mostly mild or moderate in severity, with fatigue (25%), headache (13%) and insomnia (11%) the most frequently reported. One patient had a breakthrough, 1 patient relapsed, 3 patients discontinued study drug for non‐viral failures and 1 patient was discontinued due to a drug related AE. No subjects required RBV dose reduction as per protocol Grade 1 hemoglobin‐level abnormalities were reported in 15/104 patients (14%) during the treatment period, while both grade 1 (n=9, 9%) and grade 2 (n=5, 5%) elevated total bilirubin levels were reported. Full safety data and SVR12 rates will be available at the meeting CONCLUSIONS: Preliminary data from this ongoing study demonstrate an SVR4 rate of 94% in the ITT population. The regimen was well tolerated and hemoglobin and bilirubin abnormalities were observed infrequently These preliminary results suggest that the use of low‐dose RBV with the 3‐DAA regimen may be sufficient for most patients to achieve SVR while reducing RBV‐related AEs.

Disclosures:

Fred Poordad ‐ Advisory Committees or Review Panels: Abbott/Abbvie, Achillion, BMS, Inhibitex, Boeheringer Ingelheim, Pfizer, Genentech, Idenix, Gilead, Merck, Vertex, Salix, Janssen, Novartis; Grant/Research Support: Abbvie, Anadys, Achillion, BMS, Boehringer Ingelheim, Genentech, Idenix, Gilead, Merck, Pharmassett, Vertex, Salix, Tibotec/Janssen, Novartis

Paul J. Pockros ‐ Advisory Committees or Review Panels: Janssen, Merck, BMS, Gilead, AbbVie; Consulting: Lumena, Beckman Coulter; Grant/Research Support: Intercept, Janssen, BMS, Gilead, Lumena, Beckman Coulter, AbbVie, RMS, Merck; Speaking and Teaching: AbbVie, Janssen, Gilead

Natarajan Ravendhran ‐ Grant/Research Support: BMS, GILEAD, merck, Abbvie, Salix; Speaking and Teaching: onyx, salix, Gilead, Abbvie

Michael R. Lucey ‐ Grant/Research Support: Abbvie, Gilead

Michael S. Epstein ‐ Advisory Committees or Review Panels: Aspire Bariatrics;

Consulting: abbvie, Eli Lilly, IMHEALTHSCIENCE

Leslie Bank ‐ Grant/Research Support: AbbVie Virology, Gilead, Merck, BMS; Speaking and Teaching: AbbVie Immunology, Gilead, Merck, BMS

David E. Bernstein ‐ Consulting: abbvie, Merck, Janssen; Grant/Research Support: GIlead, abbvie, BMS, Janssen; Speaking and Teaching: Gilead

Preethi Krishnan ‐ Employment: AbbVie Inc

Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott Akshanth R Polepally ‐ Employment: AbbVie

Kristina Unnebrink ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Marisol Martinez ‐ Employment: Abbvie; Stock Shareholder: Abbvie

David R. Nelson ‐ Grant/Research Support: Abbvie, BMS, Gilead, Merck, Janssen

The following people have nothing to disclose: Shahriar Sedghi, Robert Reindollar, Roger Trinh, Rajvineeth K. Pothacamury

¹Peking University Peoples Hospital, Beijing, China; ²Nanfang Hospital, Guangzhou, China; ³AbbVie Inc., North Chicago, IL; ⁴Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea (the Republic of); ⁵Taipei Veterans General Hospital, Taipei City, Taiwan; ⁶Beijing Youan Hospital Capital Medical University, Beijing, China; ⁷Pusan National University Yangsan Hospital, Yangsan, Korea (the Republic of); ⁸Beijing Di Tan Hospital, Capital Medical University, Beijing, China; ⁹Jiangsu Province Hospital, Nanjing, China; ¹⁰Beijing Friendship Hospital, Capital Medical University, Beijing, China; ¹¹Kaohsiung Medical University, Kaohsiung City, Taiwan

BACKGROUND: Previous multinational Phase 3 studies have demonstrated that treatment with the direct‐acting antiviral agents (DAAs) ombitasvir/paritaprevir (identified by AbbVie and Enanta)/ritonavir (OBV/PTV/r) and dasabuvir (DSV) was well tolerated and achieved sustained virologic response at post‐treatment week 12 (SVR12) in 100% of patients infected with genotype 1b (GT1b) hepatitis C virus (HCV) without cirrhosis. Despite these findings, interferon (IFN)/peglated IFN (pegIFN) and ribavirin (RBV) are still the current standard of care in some Asian countries where GT1b HCV infection has high prevalence. The present study evaluated the safety and efficacy of OBV/PTV/r plus DSV in adults with chronic GT1b HCV infection in Mainland China, Taiwan, and South Korea. METHODS: In th is Phase 3, randomized, double‐blind, placebo‐controlled study, the safety and efficacy of OBV/PTV/r + DSV administered for 12 weeks were evaluated in treatment‐naïve and treatment‐experienced (IFN/pegIFN and RBV), non‐cirrhotic adults with chronic GT1b HCV infection. Patients in Arm A received the active drugs during the 12 weeks of double‐blind period, while patients in Arm B received the placebo during the same period followed by the active drug treatment during the 12 weeks of open‐label period. Efficacy will be assessed by comparing the Arm A SVR12 rate with the historical SVR rate of telaprevir plus pegIFN and RBV. Safety is assessed in all patients who received at least 1 dose of study drugs. RESULTS: A total of 650 patients (Mainland China: 410; South Korea: 120; Taiwan: 120) were randomized 1:1 to Arms A and B. All patients were Asian, 54% were female and 44% were treatment experienced. As of the data cut‐off date (May 5, 2016), all South Korean and Taiwanese Arm A patients reached post‐treatment week 4 achieving an SVR4 rate of 100% Some of the Chinese patients have not yet reached post‐treatment week 4 Most treatment emergent adverse events (AEs) for patients receiving the active drug were mild in severity. The most common AEs (Arm A, B) were upper respiratory tract infection (9%, 9%), headache (5%, 4%) and dizziness (5%, 4%) Nine patients had serious AEs during the double‐blind treatment (7 in Arm A; 2 in Arm B) with only one case (in Arm A) being drug related, resulting in alanine aminotransferase elevation Two patients in Arm B discontinued treatment. CONCLUSIONS: Preliminary data from this ongoing study demonstrated a 100% SVR4 rate in HCV GT1b‐infected Korean and Taiwanese patients treated with OBV/PTV/r + DSV for 12 weeks. The regimen was well tolerated with mostly mild AEs reported. SVR12 rates from the entire study will be reported at the conference.

Disclosures:

Jinlin Hou ‐ Consulting: Roche, Novartis, GSK, BMS, Abbovir; Grant/Research Support: Roche, Novartis, GSK

Yan Luo ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Jeong Heo ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/ Research Support: BMS, Roche, GSK, Sillajen

Chi‐Jen Chu ‐ Advisory Committees or Review Panels: Gilead; Speaking and Teaching: BMS, Merck, Abbvie, Roche

Jidong Jia ‐ Consulting: Abbie, BMS, GSK, Novartis, Roche

Xinyan Zhang ‐ Employment: AbbVie

Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott Niloufar Mobashery ‐ Employment: Abbvie; Stock Shareholder: abbvie

Wan‐Long Chuang ‐ Advisory Committees or Review Panels: Gilead, Abbvie, Roche, PharmaEssentia; Speaking and Teaching: Gilead, Roche, BMS, MSD, PharmaEssentia

The following people have nothing to disclose: Lai Wei, Zhongping Duan, Mong Cho, Jun Cheng, Jun Li

¹Department of Internal Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany; ²Saint‐Antoine Hospital, Paris, France; ³Baylor College of Medicine, Houston, TX; ⁴Royal Perth Hospital, Perth, WA, Australia; ⁵Westmead Institute for Medical Research, West‐ mead Hospital, Sydney, NSW, Australia; ⁶University of Sydney, Sydney, NSW, Australia; ⁷Institute for Clinical and Experimental Medicine, Prague, Czech Republic; ⁸Royal Prince Alfred Hospital, Sydney, NSW, Australia; ⁹Toranomon Hospital, Tokyo, Japan; ¹⁰Merck & Co., Inc., Kenilworth, NJ

GT1b is the most common HCV genotype globally, accounting for the largest proportion of infections in Europe, Latin America, Russia, Turkey, and East Asia. We report the efficacy of 12 weeks of once‐daily elbasvir/grazoprevir (50 mg/100 mg) (NS5A inhibitor/NS3/4 protease inhibitor) in HCV GT1b‐in‐ fected patients enrolled in the clinical development program. This analysis of treatment‐naive and treatment‐experienced GT1b‐infected patients used data pooled from 11 trials involving 30 countries and included 1070 patients with/without cirrhosis, chronic kidney disease (CKD), and HIV co‐infection. Cirrhosis (F4, compensated) was confirmed by either liver biopsy or noninvasive tests. Patients with Stage 4 or Stage 5 CKD on hemodialysis were included. HIV/HCV co‐infected patients were required to be on a stable antiretroviral regimen (ARV) (tenofovir or abacavir, emtricitabine or lamivudine, and either raltegrevir, dolutegravir, or rilpivirine) with CD4 >200/μL and HIV viral load undetectable, or if not on ARVs, have CD4 >500/μL and viral load <50,000 lU/mL. The primary endpoint was the proportion of patients with HCV RNA below the lower limit of quantitation 12 weeks after treatment (SVR12). Efficacy data are presented for the full analysis set (FAS), which includes all patients who received at least one dose of study medication, and for the per‐protocol (PP) population, which excludes nonvirologic failures. A total of 1,070 patients were included in the analysis. Mean patient age was 53.7 years (range, 19‐80); 50% were male; 47% were white, 43% were Asian, and 9% were black or African American; 20% were treatment‐experienced; 39% had a baseline viral load >2,000,000 lU/mL; and 18% had evidence of cirrhosis. SVR12 was 97% (1040/1070) in the FAS; 15 patients (1.4%) were categorized as virologic failures and 15 (1.4%)were categorized as nonvirologic failures (lost‐to‐follow‐up or withdrawal). Excluding the nonvirologic failures, SVR12 was 99% (1040/1055) in the PP analysis. There were no notable differences in subgroup analyses: SVR12 was 97% in both treatment‐naïve and treatment‐experienced patients; 99% in cirrhotics and 97% in noncirrhotics; 98% in patients with a baseline viral load <2,000,000 lU/mL and 97% in patients with a baseline viral >2,000,000 lU/mL; 94% in HIV/HCV co‐infected patients; and 100% and 95% in patients with Stage 4 or 5 CKD, respectively. High efficacy was achieved in the GT1b‐infected population treated with elbasvir/grazoprevir for 12 weeks, with comparable efficacy across subgroups, including those with cirrhosis, high baseline viral load, and prior treatment failures.

Disclosures:

Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

Lawrence Serfaty ‐ Advisory Committees or Review Panels: MSD, Janssen, Roche, Gilead, BMS, Abbvie; Speaking and Teaching: Aptalis

John M. Vierling ‐ Advisory Committees or Review Panels: Abbvie, Bristol‐Meyers‐Squibb, Gilead, Hyperion, Intercept, Janssen, Novartis, Merck, Sundise, HepQuant, Salix, Immuron, Exalenz, Chronic Liver Disease Foundation; Board Membership: Clinical Research Centers of America, LLC; Grant/Research Support: Abbvie, Bristol‐Meyers‐Squibb, Eisai, Gilead, Hyperion, Intercept, Janssen, Novartis, Merck, Sundise, Ocera, Mochida, Immuron, Exalenz, Conatus; Speaking and Teaching: GALA, Chronic Liver Disease Foundation, ViralEd, Chronic Liver Disease Foundation, Clinical Care Options

Jacob George ‐ Advisory Committees or Review Panels: Pharmaxis, BMS, MSD, Gilead, Janssen, Abbvie; Grant/Research Support: MSD

Jan Sperl ‐ Advisory Committees or Review Panels: MSD, Abbvie, Gilead, Janssen; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: MSD, BMS, Abbvie, Gilead, Janssen

Simone I. Strasser ‐ Advisory Committees or Review Panels: AbbVie, MSD, Bristol‐Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Roche Products Australia, Bayer Healthcare, Bristol‐Myers Squibb, MSD, Gilead, Abbvie

Hiromitsu Kumada ‐ Speaking and Teaching: Bristol‐Myers Squibb,Pharma International, MSD, Abbvie, Glaxosmithkline, Gilead Sciences, Diainippon Sumitomo Pharma

Peggy Hwang ‐ Employment: Merck, Merck

Michael Robertson ‐ Employment: Merck; Stock Shareholder: Merck Janice Wahl ‐ Employment: Merck & Co,

Eliav Barr ‐ Employment: Merck; Stock Shareholder: Merck

Rohit Talwani ‐ Employment: Merck

Heather L. Platt ‐ Employment: Merck

The following people have nothing to disclose: Wendy Cheng

¹Peking University Peoples Hospital, Beijing, China; ²Peking University First Hospital, Beijing, China; ³AbbVie Inc., North Chicago, IL; ⁴Taipei Veterans General Hospital, Taipei City, Taiwan; ⁵Samsung Medical Center, Seoul, Korea (the Republic of); ⁶Nanfang Hospital of Southern Medical University, Guangzhou, China; ⁷Beijing Di Tan Hospital, Capital Medical University, Beijing, China; ⁸Ruijin Hospital Shanghai Jiaotong, University School of Medicine, Shanghai, China; ⁹Beijing Youan Hospital Capital Medical University, Beijing, China; ¹⁰National Taiwan University Hospital, Zhongzheng District, Taiwan; ¹¹Department of Internal Medicine, College of Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea (the Republic of)

BACKGROUND: Previous multinational Phase 3 studies have demonstrated that treatment with the direct‐acting antiviral agents (DAAs) ombitasvir/paritaprevir (identified by AbbVie and Enanta)/ritonavir (OBV/PTV/r) and dasabuvir (DSV) ± ribavirin (RBV) was well tolerated and achieved sustained virologic response at post‐treatment week 12 (SVR12) in 100% of patients infected with genotype 1b (GT1 b) hepatitis C virus (HCV) and with compensated cirrhosis. Despite these findings, interferon (IFN)/peglated IFN (pegIFN) and ribavirin (RBV) are still the current standard of care in some Asian countries where GT1b HCV infection has high prevalence. The present study is evaluating the safety and efficacy of OBV/PTV/r plus DSV coadministered with RBV in adults with chronic GT1b HCV infection and compensated cirrhosis in Mainland China, South Korea and Taiwan. METHODS: In this phase 3, open‐label, multi‐center study, the safety and efficacy of OBV/PTV/r plus DSV and RBV administered for 12 weeks were evaluated in treatment‐naïve and treatment experienced (IFN/pegIFN and RBV) adults with GT1b HCV Infection and compensated cirrhosis (fibrosis stage = F4). Efficacy was assessed by sustained virologic response at post treatment week 12 (SVR12) compared with the historical SVR rates of telaprevir plus pegIFN and RBV. Safety and efficacy were assessed in all patients receiving at least 1 dose of study drugs. RESULTS: A total of 104 patients (62% female, 100% Asian, 58% treatment‐experienced) were enrolled from Mainland China (n=63), South Korea (n=21) and Taiwan (n=20). All patients had chronic GT1 b HCV infection and compensated cirrhosis. As of the data cut‐off date (May 5, 2016), post‐treatment week 4 data were available for 102 patients achieving an SVR4 rate of 100%. Most Treatment Emergent Adverse Events (TEAEs) were mild in severity. The most common TEAEs (>10%) were increased blood bilirubin levels (23%), pruritus (15%), anemia (12%), asthenia (12%) and dizziness (11%). Four patients had serious TEAEs and all were assessed as not being related to the DAA regimen (one was assessed as being possibly related to RBV) One patient who achieved SVR4 discontinued treatment due to drug‐related TEAEs after 22 days of dosing (due to elevations in alanine aminotransferase, aspartate aminotransferase and blood bilirubin). CONCLUSIONS: High SVR4 rates (100%) were achieved in HCV GT1b‐infected Asian patients with compensated cirrhosis who were treated with OBV/PTV/r plus DSV and RBV for 12 weeks. The regimen was well tolerated with mostly mild TEAEs reported. SVR12 rates from the entire study will be reported at the conference.

Disclosures:

Yan Luo ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Chi‐Jen Chu ‐ Advisory Committees or Review Panels: Gilead; Speaking and Teaching: BMS, Merck, Abbvie, Roche

Jinlin Hou ‐ Consulting: Roche, Novartis, GSK, BMS, Abbovir; Grant/Research Support: Roche, Novartis, GSK

Bo Fu ‐ Employment: AbbVie

Niloufar Mobashery ‐ Employment: Abbvie; Stock Shareholder: abbvie

Jeong Heo ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/ Research Support: BMS, Roche, GSK, Sillajen

The following people have nothing to disclose: Lai Wei, Qui‐Qiang Wang, Seung Woon Paik, Jun Cheng, Qing Xie, Zhongping Duan, Jia‐Horng Kao

¹University of Pennsylvania, Philadelphia, NJ; ²Hôpital Cochin, Paris, France; ³Mercy Medical Center, Baltimore, MD; ⁴Toranomon Hospital, Tokyo, Japan; ⁵Sapporo‐Kosei General Hospital, Sapporo, Japan; ⁶Hiroshima University, Hiroshima, Japan; ⁷Dean Foundation for Health, Research and Education, Madison, WI; ⁸Texas Liver Institute and the University of Texas Health Science Center, San Antonio, TX; ⁹Hospital Italiano de Buenos Aires‐Argentina, Buenos Aires, Argentina; ¹⁰Vancouver Island Health Authority and University of British Columbia, Victoria, BC, Canada; ¹¹University of Duisburg‐Essen, Essen, Germany; ¹²University Hospital, Pisa, Italy; ¹³School of Medicine, China Medical University, Taichung, Taiwan; ¹⁴Hospital Universitario Austral, Buenos Aires, Argentina; ¹⁵Royal Prince Alfred Hospital, Sydney, NSW, Australia; ¹⁶College of Medicine, Pusan National University and Medical Research Instittue, Pusan National University Hospital, Busan, Korea (the Republic of); ¹⁷Bristol‐Myers Squibb, Wallingford, CT; ¹⁸Bristol‐Myers Squibb, Hopewell, NJ; ¹⁹Bristol‐Myers Squibb, Princeton, NJ

Background: Combinations of daclatasvir (DCV), a pangenotypic NS5A inhibitor, with other antivirals and/or peginter‐ feron/ribavirin (pegIFN/RBV) were assessed in multiple phase 2 and 3 clinical studies Here we report interim long‐term follow‐up analyses of these studies (study AI444‐046), including response durability, safety, and resistance Methods: This ongoing observational study is monitoring patients for 3 years after receiving treatment in parent studies with DCV+sofosbuvir (SOF) ±RBV, DCV+asunaprevir (ASV), DCV+ASV+beclabuvir (BCV) ±RBV, DCV+pegIFN/RBV, or DCV+ASV+pegIFN/RBV. Patients were enrolled within 6 months of parent study completion or protocol availability, and evaluated at annual to semi‐annual visits for HCV RNA levels, hepatic disease progression and decompensation events, and persistence of NS5A and NS3 resistance variants. Results: This analysis includes 893 patients treated with pegIFN‐free DCV regimens and 610 treated with pegIFN‐containing regimens. Patients were 60% male, 18% aged ≥65 years, 87% HCV genotype‐1, and 18% cirrhotic. Overall, 1329/1489 evaluable patients achieved SVR12 in parent studies; 1316/1329 (99%) maintained SVR at their most recent long‐term follow‐up visit Twelve patients relapsed after achieving SVR12 (9 on/before and 3 after posttreatment week 24); 1 patient was reinfected. Relapses after SVR12 were less frequent after treatment with all‐oral regimens (3/842, 0.4%) vs pegIFN‐based regimens (9/487, 2%). 34/1503 patients (2%) reported hepatic disease progression events during long‐term follow‐up; HCC (n=15), cirrhosis (n=8), and HCC+cirrhosis (n=2) were most common. 13 of these 34 patients did not achieve SVR12 in the parent study; 21/34 achieved and maintained SVR12. Among patients with virologic failure being monitored for up to 42 months posttreatment, replacement of NS5A and NS3 variants by wildtype sequences was observed in 27/157 (17%) and 29/41 (71%) patients, respectively. Conclusions: This interim analysis indicates that SVR12 achieved with DCV‐based regimens is durable during long‐term posttreatment follow‐up, with infrequent liver disease progression or HCC development. Further follow‐up of patients treated with DCV‐containing regimens is ongoing.

Disclosures:

K. Rajender Reddy ‐ Advisory Committees or Review Panels: Merck, Janssen, BMS, Abbvie, Gilead; Grant/Research Support: Merck, BMS, Gilead, Janssen, Abbvie

Stanislas Pol ‐ Board Membership: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/ Research Support: Gilead, Roche, MSD; Speaking and Teaching: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Roche, MSD, Novartis

Paul J. Thuluvath ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/Research Support: Gilead, AbbVie, BMS, Isai, Salix; Speaking and Teaching: AbbVie, Bayer/Onyx, Gilead

Hiromitsu Kumada ‐ Speaking and Teaching: Bristol‐Myers Squibb,Pharma International, MSD, Abbvie, Glaxosmithkline, Gilead Sciences, Diainippon Sumitomo Pharma

Kazuaki Chayama ‐ Grant/Research Support: Ajinomoto, Astellas, Asuka, MSD, Bayer, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Nihon Kayaku, Nihon Shinyaku, Kowa, Mitsubishi Tanabe, Nippon Eli Lily, Roche, Otsuka, Takeda, Toray, Torii, Tsumura, Zeria; Speaking and Teaching: Bristol‐Myers Squibb, Abbvie, Ajinomoto, Abbott, Astellas, AstraZeneca, Asuka, Chugai, Dainippon Sumitomo, Johnson and Johnson, Jimuro, Miyarisan, Nihon Kayaku, Nihon Shinyaku, Olympus, MSD

James Levin ‐ Advisory Committees or Review Panels: Gilead, Merck; Grant/ Research Support: Gilead, Merck, BMS, Abbvie; Speaking and Teaching: BMS, Gilead, Merck, Abbvie

Eric Lawitz ‐ Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals, Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol‐Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead, Janssen, AbbVie, Bristol Meyers Squibb, Merck, intercept

Maurizia R. Brunetto ‐ Advisory Committees or Review Panels: Schering‐Plough, Gilead, Janssen, AbbVie; Speaking and Teaching: Roche, Gilead, Bristol‐Myers Squibb, Abbott, Roche, Janssen

Cheng‐Yuan Peng ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, MSD, Roche

Marcelo O. Silva ‐ Advisory Committees or Review Panels: MSD, AbbVie; Grant/ Research Support: BMS, MSD, Bayer; Speaking and Teaching: BMS, AbbVie

Simone I. Strasser ‐ Advisory Committees or Review Panels: AbbVie, MSD, Bristol‐Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Roche Products Australia, Bayer Healthcare, Bristol‐Myers Squibb, MSD, Gilead, Abbvie

Jeong Heo ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/ Research Support: BMS, Roche, GSK, Sillajen

Fiona McPhee ‐ Employment: Bristol‐Myers Squibb Rong Yang ‐ Employment: BMS; Stock Shareholder: BMS Misti Linaberry ‐ Employment: BMS

Stephanie Noviello ‐ Consulting: Merck/Schering‐Plough; Employment: Bristol‐Myers Squibb, Merck/Schering‐Plough; Stock Shareholder: Merck/Schering‐Plough, J&J, Bristol‐Myers Squibb

The following people have nothing to disclose: Joji Toyota, Adrian Gadano, Wayne Ghesquiere, Guido Gerken, Zhaohui Liu

¹Mapi, Nanterre, France; ²Mapi, Uxbridge, United Kingdom; ³Chelsea and Westminster Hospital, London, United Kingdom; ⁴Royal Free Hospital, London, United Kingdom

Purpose: The aim of this study is to assess the cost‐effectiveness of treating chronic hepatitis C (HCV) infected patients at a non‐cirrhotic stage compared to treating these patients when they develop cirrhosis. Methods: A Markov model was developed to follow a cohort of 10,000 treatment‐naïve patients for a lifetime (100 years of age). Two strategies were compared: treating all patients independently of their fibrosis stage versus only treating cirrhotic patients The analysis was performed on the general patient population Age, the distribution of patients between the different fibrosis stages and costs were reflective of the UK setting. Patients were treated with ledipasvir/sofos‐ buvir (LDV/SOF) for 8 weeks in the non‐cirrhotic stages (F0 to F3) and with LDV/SOF for 12 weeks in the cirrhotic stage. The model structure is based on the models submitted to the National Institute for Health and Care Excellence (NICE) for HCV during previous health technology appraisals. Sustained virological response rates, transition probabilities, costs and utilities were obtained from the literature and the clinical trials of LDV/SOF. Costs and outcomes were discounted at 3.5% as recommended by NICE. Re‐infection was included in sensitivity analysis, as well as the proportion of patients re‐treated after re‐infection. Both deterministic and probabilistic sensitivity analyses were conducted, investigating different ranges of the parameters and alternative values collected from the literature. Onward transmission was not considered in the analysis. Results: Long‐term costs are lower and quality‐adjusted life years (QALYs) gained are higher if treatment starts at earlier stages of the disease. The results of the analysis therefore show that treating all fibrosis stages is cost‐saving (‐£1,396/QALY). The cost per cure for treating all patients is £34,164 versus £32,568 for F4. Furthermore, treating patients earlier generates fewer cases of decompensated cirrhosis, hepatocellular carcinoma, liver transplants and saves lives All results are robust to sensitivity analysis. Conclusion: This analysis demonstrates that treating HCV in early fibrosis stages, including F0 and F1, is cost‐saving in the UK. Therefore, treating patients as soon as they are diagnosed with HCV will not only generates savings, but will also reduce the burden on HCV.

Disclosures:

Lucile Marié ‐ Employment: Mapi

Ines Guerra ‐ Consulting: Gilead

Mark Nelson ‐ Advisory Committees or Review Panels: Janssen, MSD, BMS, ABBVIE, Viiv, Gilead; Consulting: Janssen, MSD, BMS, ABBVIE, Viiv, Gilead; Grant/Research Support: Boehringer Ingelheim, Janssen, MSD, BMS, ABBVIE, Viiv, Gilead, Roche; Speaking and Teaching: GSK, Janssen, MSD, BMS, Abbott, Viiv, Gilead

Sanjay Bhagani ‐ Advisory Committees or Review Panels: BMS, MSD, Abbvie, Jannsen, Gilead Sciences; Speaking and Teaching: BMS, Gilead Sciences, MSD, Jannsen, Abbvie

¹Gilead Sciences, Inc., Foster City, CA; ²University of Florida, Gainesville, FL; ³Seattle Children's Hospital, Seattle, WA; ⁴Children's Hospital Los Angeles, Los Angeles, CA; ⁵Cook Children's Health Care System, Fort Worth, TX; ⁶The Children's Hospital of Philadelphia, Philadelphia, PA; ⁷Johns Hopkins University School of Medicine, Baltimore, MD; ⁸Cincinnati Children's Hospital Medical Center, Cincinnati, OH

Background Sofosbuvir (SOF) and ledipasvir/sofosbuvir (LDV/ SOF) are approved for treatment of chronic HCV infection in adults. The safety and efficacy of SOF + ribavirin (RBV) and LDV/SOF are being assessed in adolescents receiving the adult dose. The pharmacokinetics (PK) of lower doses of SOF and LDV/SOF were evaluated in HCV‐infected children (6 to <12 y) to confirm the appropriateness of predicted doses in this population. Methods HCV‐infected children (6 to <12 y, weight ≥17 to <45 kg at screening) received SOF 200 mg QD +RBV for 7 days (N=10) or LDV/SOF 45 mg/200 mg QD for 10 days (N=10) with intensive PK assessments done on Day 7 or 10, respectively (PK lead‐in); 2 additional patients in each cohort inadvertently received adult doses SOF 400 mg or LDV/ SOF 90 mg/400 mg for 3 to 46 days. Upon completing the PK lead‐in, patients continued SOF+RBV for 12 or 24 weeks (GT‐2 or GT‐3, respectively) or LDV/SOF for 12 wks (GT‐1). SOF, GS‐331007 (major circulating metabolite) and LDV PK parameters were compared via ANOVA to exposures in Phase 2/3 SOF or LDV/SOF adult clinical programs with predefined equivalence bounds of 50‐200%. Safety was assessed throughout the study. Results All patients completed PK assessments. At screening, median (range) age (y) for patients (4 male, 8 female) on SOF+RBV was 8.5 (6, 11), weight (kg) was 31 (18, 45). Median (range) age and weight for LDV/SOF patients (8 male, 4 female) were 9 (6, 11) and 33 (20, 41), respectively Study treatments were well tolerated SOF and LDV/ SOF exposures were similar between pediatric and Phase 2/3 populations (Table 1) Conclusion Study treatments were well tolerated. SOF 200 mg +RBV or LDV/SOF 45 mg/200 mg provided comparable exposures to those observed in adults, and these data support the ongoing evaluation of these doses in children 6 to <12 y.

Disclosures:

Kimberly L. Garrison ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

Anita Mathias ‐ Employment: Gilead Sciences Inc.,

Kathryn Kersey ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

Bittoo Kanwar ‐ Employment: Gilead Sciences

Regino P. Gonzalez‐Peralta ‐ Advisory Committees or Review Panels: Shire; Consulting: Roche; Grant/Research Support: Abbvie, Gilead, Bristol Myers‐Squibb, Schering‐Plough (Merck), Sucampo

Karen F. Murray ‐ Grant/Research Support: Gilead; Stock Shareholder: Merck

Jessica Wen ‐ Grant/Research Support: Gilead, BMS, Abbvie, Novartis

Kathleen B. Schwarz ‐ Advisory Committees or Review Panels: Alexion; Grant/ Research Support: Bristol‐Myers Squibb, Gilead, Roche/Genentech, Roche

William Balistreri ‐ Grant/Research Support: Gilead

The following people have nothing to disclose: Liyun Ni, Anant Jain, John Ling, C‐H Lin, Mary Suzanne Whitworth

¹Egyptian Liver Research Institute and Hospital, Mansoura, Egypt; ²National Liver Institute, Menoufiya, Egypt; ³National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; ⁴Cairo University, Cairo, Egypt; ⁵Gilead Sciences, Inc., Foster City, CA

Background: Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection in the world, and more than 90% of patients are infected with genotype (GT) 4 virus. Ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks resulted in a SVR12 rate of 93% (41/44) in a phase 2 study conducted in France. The aims of this ongoing study are to evaluate the safety and efficacy of LDV/SOF ± ribavirin (RBV) in treatment‐naïve (TN) and ‐experienced (TE) patients in Egypt with chronic genotype (GT) 4 HCV infection. Methods: TN patients were randomized to 8 or 12 weeks of LDV/SOF± RBV and IFN‐experienced patients were randomized to 12 weeks of LDV/SOF±RBV Randomization was stratified by cirrhosis status SOF‐experienced patients receive 12 weeks LDV/SOF+RBV. The primary endpoint is SVR12. Secondary endpoints include SVR4, safety and, tolerability. Results: 170 GT4 TN Egyptian patients were enrolled and treated; 54% were male, mean (range) age 42 (21, 74), mean (range) BMI 30.4 (21.0, 50.0) kg/m², 18% had compensated cirrhosis, and 78% had IL28B non‐CC genotype. 74 IFN‐experienced and 10 SOF‐experienced patients have been enrolled to date; 76% were male, mean (range) age 50 (23, 74), mean (range) BMI kg/m² 29.3 (19.1,50.0), 27% had compensated cirrhosis, and 84% had IL28B non‐CC genotype. SVR4 rates are summarized below. In total, 6 TN patients did not achieve SVR4 due to relapse (4), rebound (n=1 ), and early study discontinuation (n=1); all TE patients to date have achieved SVR4. SVR12 data for all groups will be presented. The most common AEs (>10% of patients in any treatment group) are headache and fatigue Serious AEs have been reported for 4 patients: 3 with injuries (2 road traffic accidents, 1 arm fracture), and 1 with atypical chest pain None of the SAEs was considered related to study drug and 1 (road traffic accident) led to treatment discontinuation. Conclusions: These preliminary results support the use of LDV/SOF for 12 weeks in patients with genotype 4 HCV and the potential utility of LDV/SOF for 8 weeks in those who are treatment‐naïve.

Preliminary SVR4 rates (%; n/N) in patients with GT4 HCV who have reached 4 weeks post‐treatment

*18 IFN‐experienced and 6 SOF‐experienced patients;

NA=not applicable

Disclosures:

Imam Waked ‐ Advisory Committees or Review Panels: Janssen; Speaking and Teaching: Hoffman L Roche, BMS, Gilead, AbbVie

Mohamed Hassany ‐ Grant/Research Support: Gilead Sc, Abbvie, Janssen ; Speaking and Teaching: Abbvie

Talaat Zakareya ‐ Grant/Research Support: Gilead sciences, Inc.

Radi Hammad ‐ Grant/Research Support: Gilead Sciences,Inc, Janssen Pharmaceuticals, Inc

Kathryn Kersey ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

Benedetta Massetto ‐ Employment: Gilead Sciences, Inc. ; Stock Shareholder: Gilead Sciences, Inc

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

John G. McHutchison ‐ Employment: gilead; Stock Shareholder: gilead

Gamal E. Esmat ‐ Advisory Committees or Review Panels: MSD &BMS companies, MSD &BMS companies, Abbvie; Grant/Research Support: Gilead Sc, Abbvie ; Speaking and Teaching: Roche & GSK companies, Roche & GSK companies, Gilead Sc, Abbvie

The following people have nothing to disclose: Gamal Shiha, Reham Soliman, Wael Abdelrazek, Rabab F. Omar, Waleed Samir, Sherief Musa, Sophia Lu, Wahid H. Doss

¹Duke University, Durham, NC; ²Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain; ³ID CARE, Hillsborough, NJ; ⁴Kings College Hospital, London, United Kingdom; ⁵Auckland Clinical Studies Ltd, Auckland, New Zealand; ⁶Royal Prince Alfred Hospital, Camperdown, NSW, Australia; ⁷Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; ⁸Hospital Puerta de Hierro Majadahonda, Madrid, Spain; ⁹Gilead Sciences, Inc., Foster City, CA; ¹⁰PharPoint, Durham, NC; ¹¹London Health Sciences Centre, London, ON, Canada; ¹²Hôpital‐Saint Joseph, Marseille, France; ¹³St Louis University Hospital, St Louis, MO; ¹⁴Kansas City Research Institute, Kansas City, MO; ¹⁵Beth Israel Deaconess Medical Center, Boston, MA

Background and Aims: Significant advances in the treatment of chronic hepatitis C have been made with direct acting antiviral (DAA) regimens. While sustained virologic response (SVR) rates may now be achieved in most patients, data on long term virologic and clinical outcomes with these regimens are needed. A recent report suggested HCC incidence may not be reduced after successful DAA therapy. The objective of this ongoing registry study is to evaluate long term outcomes in patients with cirrhosis who achieved SVR following treatment with a sofosbuvir‐ (SOF) based regimen. Methods: Patients with compensated or decompensated cirrhosis who achieved SVR after receiving a SOF‐based regimen are eligible for enrollment. Patients may enroll within 60 weeks of completing a treatment study or transfer from another SVR registry study, or within 2 years of achieving SVR following treatment in a clinical practice setting. Patients return for visits every 24 weeks for 5 years. Durability of SVR and clinical outcomes (decompensation, HCC, transplantation, and liver‐related death) and laboratory parameters relating to disease progression/regression are followed in all patients. Results: 859 patients have been enrolled as of 17 May 2016. Mean age (range) is 59 (33, 83), 68% are male, and mean (range) MELD score at baseline was 8 (6, 21) and 12 (6, 24) in those with CPT A and CPT B or C cirrhosis, respectively. Median (range) time since end of treatment for clinical study patients was 373 (15, 1215) days. At baseline, SVR was maintained in 99.9% of patients (838/839); 1% (9/845) had HCC Table 1 shows changes in pretreatment CPT class to start of the registry study for those who had decompensated cirrhosis pre‐treatment Change in laboratory parameters and time to event for clinical signs through Week 72 of the registry study will be presented. Conclusions: At baseline of this registry study, SVR was maintained in 99.9% of patients with cirrhosis post‐treatment with a SOF‐based regimen. In patients with decompensated cirrhosis pretreatment, CPT class improved at entry into the registry study (from CPT B to A or from CPT C to B or A) in 65% and was unchanged in 35%. This ongoing study will provide information on whether achieving SVR following treatment with an HCV DAA regimen will improve longer term liver function and reduce the rate of liver‐related complications, including HCC.

Table 1. Number (%) of patients with CPT B or C cirrhosis prior to treatment with SOF‐based regimen by CPT class at baseline of registry study

Disclosures:

Andrew J. Muir ‐ Advisory Committees or Review Panels: Abbvie, BMS, Gilead, Janssen, Merck; Consulting: Shire, Inovia Pharmaceuticals, Intercept, Portola Pharmaceuticals; Grant/Research Support: Abbvie, BMS, Gilead, Janssen, Merck, Hologic, Intercept, NGM Biopharm, Roche

Maria Buti ‐ Advisory Committees or Review Panels: Gilead, Janssen, MSD; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, BMS

Ronald Nahass ‐ Advisory Committees or Review Panels: Gilead, Merck, Janssen, BMS; Grant/Research Support: Gilead, Merck, Janssen, BMS

Kosh Agarwal ‐ Advisory Committees or Review Panels: Gilead, BMS, Novartis, Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead, BMS, GSK

Edward J. Gane ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead Sciences, Achillion, Merck; Speaking and Teaching: AbbVie, Gilead Sciences, Merck, Alnylam

Simone I. Strasser ‐ Advisory Committees or Review Panels: AbbVie, MSD, Bristol‐Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Roche Products Australia, Bayer Healthcare, Bristol‐Myers Squibb, MSD, Gilead, Abbvie

Alessandra Mangia ‐ Advisory Committees or Review Panels: Gilead Sciences, BMS, Shering‐Plough, MSD, Boheringer, BMS; Board Membership: MSD; Grant/ Research Support: Janssen, Janssen, Gilead; Speaking and Teaching: ROCHE

Jose L. Calleja ‐ Advisory Committees or Review Panels: Gilead, Abbvie ; Speaking and Teaching: Abbvie, Gilead, Janssen, BMS

Kathryn Kersey ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Marc Bourlière ‐ Advisory Committees or Review Panels: Schering‐Plough, Bohringer inghelmein, Schering‐Plough, Bohringer inghelmein, Transgene; Board Membership: Bristol‐Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis, Tibotec, Abott, glaxo smith kline, Merck, Bristol‐Myers Squibb, Novartis, Tibotec, Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol‐Myers Squibb

Bruce Bacon ‐ Advisory Committees or Review Panels: Gilead, Bristol‐Meyers Squibb, ISIS, Abbvie, Janssen; Consulting: Merck; Grant/Research Support: Merck, Gilead, Bristol‐Meyers Squibb, Abbvie; Speaking and Teaching: Merck, Gilead, Abbvie, Salix, Janssen

Bradley Freilich ‐ Grant/Research Support: schering plough, vertex, roche, abbott, pharmaset, anadys, abbott, schering plough, vertex, roche, abbott, pharmaset, anadys, abbott, schering plough, vertex, roche, abbott, pharmaset, anadys, abbott, schering plough, vertex, roche, abbott, pharmaset, anadys, abbott, connatus, bristol myers, jansen, gilead; Speaking and Teaching: onyx, onyx, onyx, onyx, gilead, jansen, abbott

Michael P. Curry ‐ Consulting: Alexion, Bristol Meyers Squib, Abbvie; Grant/ Research Support: Gilead Sciences, Conatus

The following people have nothing to disclose: Stephanie Moody, Paul Marotta

¹Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; ²Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hanover, Germany; ³Dept.of Gastroenterology and Rheumatology, University Hospital Leipzig, Leipzig, Germany; ⁴J.W. Goethe University Frankfurt, Frankfurt, Germany; ⁵ifi‐institute for interdisciplinary medicine, Hamburg, Germany; ⁶e.factum GmbH, Butzbach, Germany; ⁷Center of Hepatology, Hanover, Germany; ⁸Universitätsklinikum Schleswig‐Holstein (UKSH), Campus Kiel, Kiel, Germany; ⁹University Hospital Würzburg, Wuerzburg, Germany; ¹⁰Charite Campus Virchow‐Klinikum (CVK), Berlin, Germany; ¹¹Center of Gastroenterology, Herne, Germany; ¹²Leberstiftungs‐GmbH Deutschland, Hanover, Germany

Introduction: In pivotal studies with modern direct acting antivirals (DAA) SVR rates in HCV genotype 1 (GT1) are >90%. However these data have to be replicated in less well controlled settings including patients more difficult to treat Methods: The German Hepatitis C Registry is a national multicentre real‐world cohort Patients are treated at the discretion of the physician Data are collected by a web‐based system. Data quality is analyzed by plausibility checks and on site monitoring. This data analysis is based on 6,034 patients who were observed for at least 40 weeks after initiation of antiviral treatment. Results: Between 2/2014 and 5/2015, 5,110 patients with GT1 have been enrolled. SVR12 data are available for 3,439 patients at the time of analysis Demographics: 56% male, median age 55 years, 98% Caucasian, 52% treatment experienced, 30% liver cirrhosis, 10% HCV‐RNA >6 Mio lU/mL. Comorbidities were reported for 75% of the patients in the cohort: cardiovascular 27%, psychiatric 15%, drug abuse 13%, diabetes 10%, thyroid dysfunction 10% being the most frequent. Patients treated with one of the approved regimens for GT1 were analysed (table 1). SVR12 overall in GT1a was 91% and in GT1b 93%. In multivariate analysis adjusting for age, sex, platelets, cirrhosis, HCV RNA, GT1a/1b and treatment regime, SVR12 was associated with the choice of antiviral regimen (OR 1.48 (1.37‐1.60); p<0.001), cirrhosis (OR 0.60 (0.45‐0.80); p<0.001) and higher age (OR 1.49 (1.08‐2.07); p<0.05). HIV‐coinfected patients (n=247) had an overall SVR12 of 93% not substantially different from HCV‐monoinfected patients Adverse events were reported by 53% of patients with fatigue (23%), headache (16%), nausea (7%) and insomnia (6%) being the most frequent Serious adverse event were observed in 3% and 16 patients (0.3%) died. Conclusions: Data from this real life cohort show SVR 12 rates close to those obtained in clinical studies. Choice of antiviral therapy was associated with treatment outcome. In addition higher age was a positive factor and presence of cirrhosis a negative factor for achieving SVR12. Dropout rates were low confirming good adherence of patients with these regimens.

Table 1. Treatment regimens and SVR12 data of patients with HCV GT1 (ITT)

Disclosures:

Stefan Mauss ‐ Advisory Committees or Review Panels: BMS, AbbVie, ViiV, Gilead; Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD

Peter Buggisch ‐ Advisory Committees or Review Panels: Janssen, AbbVie, BMS; Speaking and Teaching: Falk, MSD, Gilead, Merz Pharma

Klaus H. Boeker ‐ Consulting: Janssen; Speaking and Teaching: MSD, Roche, Gilead, BMS, Falk Foundation, Novartis, AbbVie

Eckart Schott ‐ Advisory Committees or Review Panels: Gilead, Roche, Bayer, BMS, Abbvie, Janssen, MSD; Speaking and Teaching: Gilead, Novartis, Roche, MSD, Bayer, Falk, BMS, Janssen, Abbvie

Hartwig H. Klinker ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, Hexal, Janssen, MSD; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, MSD, Arrowhead, Novartis; Speaking and Teaching: AbbVIe, BMS, Gilead, Janssen, MSD

Rainer Günther ‐ Speaking and Teaching: Roche Pharma AG, Gilead, AbbVie

Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Thomas Berg ‐ Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis, Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Merck/MSD, Novartis, Merck, Bayer, Abbvie

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

Dietrich Hueppe ‐ Advisory Committees or Review Panels: Roche, MSD, Novatis, Gilead, BMS, Janssen, AbbVie

Michael P. Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie Deutschland GmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

Virginia Commonwealth University, Richmond, VA

Chronic HCV is prevalent in the DOC. Although SVR with DAA treatment (tx) is high, feasibility and SVR of patients (pt) in the DOC are unknown. We compared SVR12 in the Virginia DOC with DAAs through telemedicine to HCV pts in our privately‐insured and indigent clinics treated with Ledipasvir/Sofosbuvir. Methods: DOC pts were evaluated via telemedicine for disease severity and appropriateness for tx following AASLD‐IDSA Guidelines. Those with decompensated cirrhosis, significant co‐morbidities, or those with less than 9 months on their sen‐tence we excluded. Demographic, baseline labs, HIV and prior tx status (naïve (TN) or experienced (TE)), % advanced fibrosis (AF, bridging fibrosis/cirrhosis), duration of tx, use of ribavirin (RBV), and SVR12 (the primary outcome) were recorded. We compared SVR12 in our DOC pts to 2 control groups: our privately‐insured and indigent tx clinics during the same time period by the same providers We excluded those with non‐genotype (GT)1 (n= 45) and those GT1 treated with other DAAs (n=16). Results: 255 consecutive pts were included: 50 DOC pts were compared to 161 private and 44 indigent pts who had SVR12 data available. The characteristics of our populations and SVR12 are shown in the table. Those in the DOC were younger, male, TN, had AF, received RBV and 12 weeks of tx. SVR12 was 98% in the DOC and similar to our indigent (98%) compared to our private clinics (89%; p=.02) even when those who were lost to follow up were excluded (SVR12 91%). Multiple logistic regression identified treatment clinic (p=.02) and FIB‐4 (.0002) as predictors of lack of SVR12 with no impact of race, gender, age, duration or prior tx history, RBV use, or HIV. Conclusions: Tx of HCV in the DOC by telemedicine with DAA is not only feasible, but has a very high SVR12. The higher SVR12 in the DOC compared to our private clinic may be due to directly observed therapy or differences in pt characteristics (lower FIB‐4, a marker of disease severity). Additional data with longer follow up in the DOC are needed.

Disclosures:

Richard K. Sterling ‐ Advisory Committees or Review Panels: Merck, Baxter, Salix, Bayer, BMS, AbbVie, Gilead, GSK, Jansen; Grant/Research Support: Merck, Roche/Genentech, Pfizer, Gilead, Bayer, BMS, AbbVie

Velimir A. Luketic ‐ Advisory Committees or Review Panels: GSK; Grant/Research Support: INTERCEPT, LUMENA/SHIRE, MERCK, GILEAD, GENFIT, BMS, ABVIE, NGM

Arun J. Sanyal ‐ Advisory Committees or Review Panels: Bristol Myers, Gilead, Genfit, Abbott, Ikaria, Exhalenz, Pfizer, Novartis; Consulting: Salix, Immuron, Exhalenz, Nimbus, Genentech, Echosens, Takeda, Merck, Enanta, Zafgen, JD Pharma, Islet Sciences, Hemoshear; Grant/Research Support: Salix, Genentech, Intercept, Ikaria, Takeda, GalMed, Novartis, Gilead, Tobira; Independent Contractor: UpToDate, Elsevier; Management Position: Sanyal Biotechnology

The following people have nothing to disclose: Reena Cherian, Lewis Shawn, Ravi Chhatrala, Anas Alsaleh, Kathleen Genther, Carloyn Driscoll, Kelly Martin, Scott C. Matherly, Mohammad Siddiqui, R. Todd Stravitz, Puneet Puri, Hannah Lee, Paula G. Smith

¹ifi‐institute for interdisciplinary medicine, Hamburg, Germany; ²Center of Hepatology, Hannover, Germany; ³Department of Internal Medicine I, UK S‐H, Campus Kiel, Kiel, Germany; ⁴Center of Hepatology, Frankfurt, Germany; ⁵University Hospital Würzburg, Würzburg, Germany; ⁶Internal Medicine IV, Gastroenterology and Hepatology, University Clinic of Heidelberg, Heidelberg, Germany; ⁷Center for interdisciplinary Medicine (CIM), Muenster, Germany; ⁸e.factum GmbH, Butzbach, Germany; ⁹MVZ Dr.Eisenbach Dr.Simon Dr.Schwarz GbR, Leverkusen, Germany; ¹⁰St. Josef‐Hospital, Katholisches Klinikum Oberhausen, Oberhausen, Germany; ¹¹Gastroenterology,Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; ¹²Department of Internal Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany; ¹³Leberstiftungs‐GmbH Deutschland, Hannover, Germany

Introduction: Ledipasvir/Sofosbuvir (LDV/SOF) for 8‐24 weeks is approved for the treatment of chronic hepatitis C. In the ION‐3 study 8 weeks of LDV/SOF was non‐inferior to 12 wks in previously untreated GT1 patients without cirrhosis. Although the number of patients eligible for 8 weeks according to the summary of product characteristics (SmPC) is high, a large proportion of patients still receives a longer treatment duration. One of the reasons might be the uncertainty whether 8 weeks treatment duration is sufficient in harder to cure populations as HIV co‐infected patients, patients on opioid substitution treatment (OST) or older patients (> 70 yrs.). Aim of this analysis was to evaluate the virologic response rates of 8 wks treatment under real world conditions in these patients. Methods: The German Hepatitis C registry is a national multicenter cohort. Patients are treated at the discretion of the physician Data are collected by a web‐based data system and confirmed by plausibility checks and on site monitoring. In this analysis data of patients with 8 or 12 wks treatment with LDV/SOF and available SVR12 data (data cut 2/2016) were included. Baseline characteristics, prior treatment history, safety and effectiveness were investigated. Results: 831 (433 female) pts were treated for 8 weeks. The mean (SD) age was 50.2 (12.9) yrs. In 37% the fibrosis stage was evaluated by elastography (Fibroscan®), the mean (SD) stiffness value was 6.5 kPa (2.4). 674 pts reached the SVR 12 time point and were included in the analysis. Genotype distribution was 99.1% for GT1 and 0.9% for GT4. Baseline viral load was > 6 Mio IU/mL in 2,7%, 8,6% were treatment experienced and 2.5% had liver cirrhosis and were treated for 8 weeks despite these characteristics. The overall SVR 12 rate was 93% (ITT) and 98% (PP). 59 (8.8%) pts had HIV co‐infection. SVR 12 in this group was 93.2% (ITT) and 96.6% (PP), only 2 viral relapses occurred. 72 pts received OST, only 1 pt developed viral relapse. 5 pts discontinued therapy and 5 were lost to follow up, thus, SVR12 was 84.7% (ITT) and 98.6% (PP) compared to 94.5% (ITT) and 97.9% (PP) without OST. 48 pts were >70 yrs. with SVR12 rates of 95.8% (ITT) and 97.9% (PP). 65 pts who were pretreated achieved SVR12 rates of 90.8% (ITT) and 95.2% (PP). Conclusions: Under real world conditions, 8 wks LDV/SOF achieves very high SVR rates in heterogeneous groups like HIV co‐infected pts and in other so called harder to cure populations

Disclosures:

Peter Buggisch ‐ Advisory Committees or Review Panels: Janssen, AbbVie, BMS; Speaking and Teaching: Falk, MSD, Gilead, Merz Pharma Klaus H. Boeker ‐ Consulting: Janssen; Speaking and Teaching: MSD, Roche, Gilead, BMS, Falk Foundation, Novartis, AbbVie

Rainer Günther ‐ Speaking and Teaching: Roche Pharma AG, Gilead, AbbVie Gerlinde Teuber ‐ Advisory Committees or Review Panels: MSD, Gilead, Abbvie; Grant/Research Support: Gilead, Abbvie, Falk; Speaking and Teaching: MSD, Gilead, BMS, Abbvie, Janssen

Hartwig H. Klinker ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, Hexal, Janssen, MSD; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, MSD, Arrowhead, Novartis; Speaking and Teaching: AbbVIe, BMS, Gilead, Janssen, MSD

Anita Pathil ‐ Speaking and Teaching: AbbVie, BMS, Gilead

Stefan Christensen ‐ Advisory Committees or Review Panels: BMS, Abbvie, Janssen, ViiV, Gilead, MSD; Speaking and Teaching: Gilead, MSD, Abbvie, BMS, Janssen

Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Karl‐Georg Simon ‐ Advisory Committees or Review Panels: AbbVie, BMS, JANSSEN, MSD; Speaking and Teaching: AbbVie, BMS, FALK, GILEAD, JANSSEN, NORGINE, MERZ, MSD

Claus Niederau ‐ Advisory Committees or Review Panels: MSD, Abbvie, Jannsen, Gilead; Consulting: MSD; Grant/Research Support: MSD; Speaking and Teaching: MSD, Abbvie, BMS, Roche, Gilead

Heiner Wedemeyer ‐ Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics, Eiger; Consulting: MyrGmbH; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics; Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead

Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie Deutschland GmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

¹University of Alberta, Edmonton, AB, Canada; ²Kings College Hospital, London, United Kingdom; ³Barts Health, Queen Mary University of London, London, United Kingdom; ⁴Liver Unit, Auckland City Hospital, Auckland, New Zealand; ⁵AbbVie, Inc., North Chicago, IL; ⁶Royal Adelaide Hospital, Adelaide, SA, Australia

Background Hepatitis C virus (HCV) genotypes (GT) 2 and 3 account for an estimated 40% of global HCV infections. GT3 is the most difficult to cure with direct‐acting antiviral (DAA) therapy, especially in patients with cirrhosis or prior treatment failure. We previously presented safety and efficacy of ombit‐ asvir (NS5A inhibitor) co‐formulated with the protease inhibitor paritaprevir (identified by Abbvie and Enanta) and ritonavir (OBV/PTV/r; 2D) plus sofosbuvir (SOF) ± ribavirin (RBV) in 20 GT3‐infected patients (QUARTZ‐II/III Arms A and B). Here we investigate the safety and efficacy of 6‐ and 8‐week treatment durations of 2D+SOF+RBV in 18 GT2‐infected patients, and assess 12‐week 2D+SOF± RBV in 20 additional GT3‐infected patients, including those with cirrhosis. Methods QUARTZ II‐III (NCT02292719) is an open‐label, multicenter study. GT2‐in‐ fected patients received OBV/PTV/r 50/150/100mg + SOF 400mg ± weight‐based RBV for 8 (Arm C) or 6 (Arm D) weeks. GT3‐infected patients with cirrhosis (Arm E) received 2D+SOF+RBV for 12 weeks; GT3‐infected patients without cirrhosis received 2D+SOF with (Arm B) or without (Arms A+F) RBV for 12 weeks. The primary efficacy endpoint is the percentage of patients achieving SVR12. Results The study enrolled 70 patients. Table 1 shows select baseline demographics, efficacy, & safety data for 54 patients. As of post‐treatment week 4 (PTW4), 35/37 (95%) patients with available data had HCV RNA<LLOQ. Two GT2‐infected patients, one each in Arm C (8 weeks) and Arm D (6 weeks), experienced relapse at PTW4. To date, there have been no virologic failures in patients with GT3 infection, regardless of cirrhosis status The most common AEs were fatigue (42%), headache (36%), nausea (24%), and diarrhea (20%). No serious AEs were related to DAAs and no DAA‐related AEs led to discontinuation of study drug. Conclusions 2D+SOF±RBV was well tolerated in patients with GT2 or 3 infection, and most patients achieved SVR4 Complete SVR12, resistance, and safety data will be presented.

Table 1. Baseline Demographics, Safety and SVR4

Disclosures:

Stephen Shafran ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead Sciences, Merck; Grant/Research Support: AbbVie, Bristol‐Myers Squibb, Gilead Sciences, Janssen, Merck; Speaking and Teaching: Pfizer

Mariem Charafeddine ‐ Employment: AbbVie Ltd; Stock Shareholder: AbbVie Ltd

Kosh Agarwal ‐ Advisory Committees or Review Panels: Gilead, BMS, Novartis, Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead, BMS, GSK

Graham R. Foster ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS, Alnylam; Board Membership: Boehringer Ingelheim; Grant/Research Support: Roche, Chughai, Springbank; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen

Manal Abunimeh ‐ Employment: AbbVie

Bo Fu ‐ Employment: AbbVie

Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott

Daniel E. Cohen ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Edward J. Gane ‐ Advisory Committees or Review Panels: AbbVie, Janssen, Gilead Sciences, Achillion, Merck; Speaking and Teaching: AbbVie, Gilead Sciences, Merck, Alnylam

The following people have nothing to disclose: David Shaw, Rajvineeth K. Pothacamury, Eric Cohen

¹Baylor‐St. Luke's Medical Center/St. Luke's Advanced Liver Therapies, Houston, TX; ²The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; ³University of Pennsylvania, Philadelphia, PA; ⁴AbbVie Inc., North Chicago, IL; ⁵Tampa General Medical Group, Tampa, FL; ⁶University of Florida Health Science Center, Gainesville, FL; ⁷Carolinas Medical Center, Charlotte, NC; ⁸Medical Associates Research Group, San Diego, CA; ⁹North Shore University Hospital, Manhasset, NY; ¹⁰Swedish Medical Center, Seattle, WA; ¹¹ The Liver Institute at Methodist Dallas, Dallas, TX; ¹²Scripps Clinic, Scripps Clinic, LaJolla, CA; ¹³University of California San Diego, LaJolla, CA; ¹⁴Weill Cornell Medical College, New York, NY; ¹⁵University of Miami, Miami, FL; ¹⁶Southern California GI and Liver Centers and Southern California Research Center, Coronado, CA

BACKGROUND: Combinations of direct acting antiviral agents (DAAs) have demonstrated high rates of sustained virologie response (SVR) in patients with chronic hepatitis C virus (HCV) infection in compensated cirrhotics and non‐cirrhotics. However, clinical data are limited for DAAs in patients with comorbid renal dysfunction. RUBY‐I is a phase 3b, open‐label, multi‐center study assessing the safety and efficacy of OBV/ PTV/r + DSV ± RBV in GT1 HCV‐infected patients with severe renal impairment or end‐stage renal disease, including dialysis Results from the first cohort were previously presented; here we present safety and efficacy data from the second cohort (Arms C‐E), including patients with compensated cirrhosis. METHODS: Participants were either treatment naïve (TN) or treatment experienced (TE) with IFN/pegIFN and RBV. Patients with GT1a HCV infection and fibrosis stages <F4 were assigned to Arm C and received the 3‐DAA regimen with RBV 200 mg QD for 12 weeks, while those with fibrosis stage F4 were assigned to Arm D and treated with the same regimen for 24 weeks. Patients with GT1b HCV infection with fibrosis stages F0‐F4 were assigned to Arm E and treated with the 3‐DAA regimen without RBV for 12 weeks. Efficacy is assessed by SVR at post‐treatment week 12 (SVR12). Safety is assessed in all patients who received at least 1 dose of the study drugs. RESULTS: A total of 48 patients with chronic HCV infection (31% with and 69% without cirrhosis) and with severe renal impairment or end stage renal disease were enrolled in this cohort: 28 in Arm C, 9 in Arm D and 11 in Arm E. Among them, 83% were male and 54% were black. All patients had either stage 4 (17%) or 5 chronic kidney disease, including 69% on hemodialysis. As of the data cut‐off date (May 5, 2016), SVR4 was achieved in 29/31 (94%) patients (16/17, 2/3 and 11/11 in Arms C, D and E, respectively) in the intent‐to‐treat population. Both patients not achieving SVR4 prematurely discontinued treatment. Most treatment emergent adverse events (AEs) were mild or moderate in severity, with anemia (27%), decreased hemoglobin (23%) and fatigue (21%) the most frequently reported. Ten patients experienced serious AEs and one patient discontinued treatment in each of Arms C and D. CONCLUSIONS: Preliminary data from this ongoing study demonstrated an SVR4 rate of 94% Most AEs were mild or moderate in severity These results support the use of this regimen in patients with advanced renal disease, for whom treatment options are limited.

Disclosures:

John M. Vierling ‐ Advisory Committees or Review Panels: Abbvie, Bristol‐Meyers‐Squibb, Gilead, Hyperion, Intercept, Janssen, Novartis, Merck, Sundise, HepQuant, Salix, Immuron, Exalenz, Chronic Liver Disease Foundation; Board Membership: Clinical Research Centers of America, LLC; Grant/Research Support: Abbvie, Bristol‐Meyers‐Squibb, Eisai, Gilead, Hyperion, Intercept, Janssen, Novartis, Merck, Sundise, Ocera, Mochida, Immuron, Exalenz, Conatus; Speaking and Teaching: GALA, Chronic Liver Disease Foundation, ViralEd, Chronic Liver Disease Foundation, Clinical Care Options

Eric Lawitz ‐ Advisory Committees or Review Panels: AbbVie, Achillion Pharmaceuticals, Regulus, Theravance, Enanta, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Gilead; Grant/Research Support: AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol‐Myers Squibb, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Nitto Denko, Theravance, Salix, Enanta; Speaking and Teaching: Gilead, Janssen, AbbVie, Bristol Meyers Squibb, Merck, intercept

K. Rajender Reddy ‐ Advisory Committees or Review Panels: Merck, Janssen, BMS, Abbvie, Gilead; Grant/Research Support: Merck, BMS, Gilead, Janssen, Abbvie

Philippe J. Zamor ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead; Grant/Research Support: Gilead, AbbVie, Merck; Speaking and Teaching: Bristol Myers Squibb, Gilead, AbbVie

David E. Bernstein ‐ Consulting: abbvie, Merck, Janssen; Grant/Research Support: GIlead, abbvie, BMS, Janssen; Speaking and Teaching: Gilead

Kris V. Kowdley ‐ Advisory Committees or Review Panels: Abbvie, Enanta, Gilead, Intercept, Merck, Novartis, Trio Health, Verylx; Grant/Research Support: Abbvie, Evidera, Galectin, Gilead, Immuron, Intercept, Merck, NGM Biopharma, Novartis, Tobira, Trio Health; Speaking and Teaching: Gilead, Intercept

Parvez S. Mantry ‐ Consulting: Salix, Gilead, Janssen, Abbvie, BMS; Grant/ Research Support: Salix, Merck, Gilead, Boehringer‐Ingelheim, Mass Biologics, Vital Therapies, Santaris, mass biologics, Bristol‐Myers Squibb, Abbive, Bayer‐Onyx, Shinogi, Tacere, Intercept; Speaking and Teaching: Gilead, Janssen, Salix

Paul J. Pockros ‐ Advisory Committees or Review Panels: Janssen, Merck, BMS, Gilead, AbbVie; Consulting: Lumena, Beckman Coulter; Grant/Research Support: Intercept, Janssen, BMS, Gilead, Lumena, Beckman Coulter, AbbVie, RMS, Merck; Speaking and Teaching: AbbVie, Janssen, Gilead

David L. Wyles ‐ Advisory Committees or Review Panels: Bristol Myers Squibb, Gilead, Merck, AbbVie; Grant/Research Support: Gilead, Merck, Bristol Myers Squibb, AbbVie, Tacere

Sonal Kumar ‐ Advisory Committees or Review Panels: Gilead, Intercept, Abbvie; Speaking and Teaching: Intercept, Gilead

Kalyan R. Bhamidimarri ‐ Advisory Committees or Review Panels: Gilead, Bristol Myers Squibb, Salix; Speaking and Teaching: Alexion

Daniel E. Cohen ‐ Employment: AbbVie; Stock Shareholder: AbbVie Tami Pilot‐Matias ‐ Employment: AbbVie; Stock Shareholder: Abbott Wangang Xie ‐ Employment: AbbVie

Thomas Podsadecki ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Tarek I. Hassanein ‐ Advisory Committees or Review Panels: AbbVie Pharmaceuticals, Bristol‐Myers Squibb, Trek Therapeutics; Grant/Research Support: AbbVie Pharmaceuticals, Obalon, Bristol‐Myers Squibb, Eiasi Pharmaceuticals, Gilead Sciences, Merck Sharp & Dohme, NGM BioPharmaceuticals, Ocera Therapeutics, Salix Pharmaceuticals, Sundise, TaiGen Biotechnology, Vital Therapies, Tobria, Shinoghi & Co Ltd, La Jolla Pharmaceuticals, Trek Therapeutics, Novo Nordisk, Intercept; Speaking and Teaching: Baxter, Bristol‐Myers Squibb, Gilead Sciences, Salix Pharmaceuticals, AbbVie Pharmaceuticals

The following people have nothing to disclose: Eric Cohen, Nyingi Kemmer, Giuseppe Morelli, Michael Bennett

¹Gastroenterology and Hepatology, Eastern Health, Melbourne, VIC, Australia; ²Gastroenterology, Alfred Health, Melbourne, VIC, Australia; ³Gastroenterology, Monash Health, Melbourne, VIC, Australia; ⁴Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia; ⁵University of Melbourne, Melbourne, VIC, Australia; ⁶Eastern Health Clinical School, Monash University, Melbourne, VIC, Australia; ⁷AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia; ⁸HIV, Immunology, Infectious Diseases Department, St Vincent's Hospital, Sydney, NSW, Australia; ⁹Gastroenterology, Princess Alexandra Hospital, Brisbane, QLD, Australia; ¹⁰Storr Liver Centre, Westmead Institute for Medical Research, Sydney, NSW, Australia; ¹¹University of Sydney, Sydney, NSW, Australia; ¹²Gastroenterology, Royal Adelaide Hospital, Adelaide, VIC, Australia; ¹³Gastroenterology, St Georges Hospital, Sydney, NSW, Australia; ¹⁴Gastroenterology, Liverpool Hospital, Sydney, NSW, Australia; ¹⁵Gastroenterology, Sir Charles Gairdner Hospital, Perth, WA, Australia; ¹⁶Gastroenterology, Nepean Hospital, Sydney, NSW, Australia; ¹⁷Victorian Liver Transplant Unit, Austin Health, Melbourne, VIC, Australia; ¹⁸VIDS and Peter Doherty Institute, Royal Melbourne Hospital, Melbourne, VIC, Australia; ¹⁹Gastroenterology, Royal Perth Hospital, Perth, WA, Australia; ²⁰Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia; ²¹Infectious Diseases, Barwon Health, Geelong, VIC, Australia

Background and Aims In October 2015 the FDA released a warning on the use of ritonavir‐boosted paritaprevir, with ombitasvir and dasabuvir (PrOD) +/‐ ribavirin in patients with cirrhosis. Consequently PrOD is now contraindicated in patients with Child‐Turcotte Pugh class B/C hepatic impairment. Both hyperbilirubinemia and elevated ALT concentrations have been observed during therapy but the severity and clinical significance of these abnormalities in a real‐world setting have not been reported. The aims of this study were to characterize the bilirubin and ALT changes observed during PrOD therapy in a large real‐world population and to determine the impact of these changes on outcome (SVR12 and early discontinuation of therapy). Methods Patients who participated in an Australian compassionate access program to treat hepatitis C between October 2014 and July 2015 were included in the analysis if they received at least one dose of PrOD. Elevations in bilirubin were characterized in accordance with the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Results There were 461 patients included in this analysis. The majority had cirrhosis (74%). In the 88% of cirrhotic patients with complete response data, the SVR12 was 95.5%. Hyperbilirubinemia on PrOD was very common with elevated values ≥ 2mg/dL (34pmol/L) occurring in 45.1 % of subjects (Table 1). A small proportion of patients had mild elevation (≥2mg/dL in 6.5%) prior to comemncing. In the 9 patients that experienced elevations in bilirubin >10 mg/dL, all were cirrhotic, 89% developed hyperbilirubinemia within the first 4 weeks of therapy and 78% ceased therapy early (mean 4.79 weeks ± 1.5). In most instances the ALT diminished on PrOD (88%, mean 58 IU/L ±4.4), however in 11 patients (2.4%) there was an increase in ALT of at least 100 IU/L from baseline. This was not associated with hyperbilirubinemia and 73% were cirrhotic with SVR12 of 80%. Conclusions In this real‐world study of HCV genotype 1 patients mostly with cirrhosis, SVR12 rates were excellent. Hyperbilirubinemia occurred commonly but in most instances the abnormality was only mild‐moderate and did not lead to discontinuation or significantly impact upon SVR 12.In a small proportion of patients the bilirubin exceeded 10mg/dL and this frequently resulted in early discontinuation.

Maximum bilirubin increase on PrOD

Disclosures:

John Lubel ‐ Advisory Committees or Review Panels: Gilead, Abbvie, Bayer; Grant/Research Support: BMS, MSD, Abbvie; Speaking and Teaching: Gilead, Abbvie, BMS, Jansen, Roche

Stephen Pianko ‐ Advisory Committees or Review Panels: Roche, Novartis, GILEAD, Roche, Novartis; Consulting: GILEAD; Speaking and Teaching: JANSSEN, BMS

Alex J. Thompson ‐ Advisory Committees or Review Panels: Gilead, Abbvie, BMS, Merck, Spring Bank Pharmaceuticals, Arrowhead, Roche; Grant/Research Support: Gilead, Abbvie, BMS, Merck; Speaking and Teaching: Roche, Gilead, Abbvie, BMS

David M. Iser ‐ Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck, Roche

Simone I. Strasser ‐ Advisory Committees or Review Panels: AbbVie, MSD, Bristol‐Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Roche Products Australia, Bayer Healthcare, Bristol‐Myers Squibb, MSD, Gilead, Abbvie

Gregory Dore ‐ Board Membership: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Grant/Research Support: Gilead, Merck, Abbvie, Bristol‐Myers Squibb; Speaking and Teaching: Gilead, Merck, Abbvie, Bristol‐Myers Squibb

Katherine A. Stuart ‐ Advisory Committees or Review Panels: Gilead, Bayer, AbbVie; Grant/Research Support: Roche

Jacob George ‐ Advisory Committees or Review Panels: Pharmaxis, BMS, MSD, Gilead, Janssen, Abbvie; Grant/Research Support: MSD

Amany Zekry ‐ Advisory Committees or Review Panels: GILEAD, BMS, MSD, Abbvie

Miriam Levy ‐ Advisory Committees or Review Panels: Bayer; Grant/Research Support: Gilead

Vince Fragomeli ‐ Advisory Committees or Review Panels: Roche, MSD, Jansen

Brenda Morales ‐ Advisory Committees or Review Panels: MSD, Jansen, Roche, Abbvie, BMS

Joe Sasadeusz ‐ Advisory Committees or Review Panels: Merck, Gilead, BMS; Grant/Research Support: Roche, Gilead, Avvbie; Speaking and Teaching: Gilaed, Merck, BMS, Merck

Amanda J. Wade ‐ Grant/Research Support: AbbVie

Stuart K. Roberts ‐ Board Membership: AbbVie, Gilead

The following people have nothing to disclose: Joanne Mitchell, Alessia Gazzola, Sarah Chivers, Gauri Mishra, John Gough, Edmund Tse, Gerry C. MacQuillan, Paul Gow, Saroj Nazareth, Steven J. Bollipo, Tracey L. Jones

¹Pharmacogenetics and Pharmacogenomics, AbbVie, North Chicago, IL; ²AbbVie, North Chicago, IL; ³Division of Infectious Disease, Univ. Gothenberg, Gothenburg, Sweden

Background: Genetic variants of the inosine triphosphatase (I7PA) gene that confer reduced ITPase activity have been associated with protection against ribavirin‐induced hemolytic anemia in peginterferon (IFN)/ribavirin‐based treatment of hepatitis C virus (HCV). Studies in patients treated with IFN/ ribavirin have shown improved treatment efficacy in patients with reduced ITPase activity. Ribavirin has been an important component of IFN‐containing regimens, and is currently recommended in combination with several IFN‐free regimens for treatment of HCV infections. In the present study, genetic analyses were conducted to interrogate the effect of these ITPA variants on anemia, platelet counts, and virologic response in HCV genotype la‐infected subjects treated with the direct‐acting antiviral (DAA) regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin. Methods: DNA samples were obtained from appropriately consented subjects enrolled in the PEARL‐IV study (NCT01833533) and analyzed for ITPA variants rs7270101 and rsl 127354 using pyrosequencing. Results: Reduction in ITPase activity protected against ribavirin‐induced anemia, an effect that was more significant when gender was added as a covariate in the analyses. Male subjects with lower ITPase activity were protected against ribavirin‐induced anemia (Hb change ‐0.92 g/dL in low ITPase vs. ‐2.65 g/dL in high ITPase; p=0.0013), whereas no such significant association was noted among female subjects (‐0.92 g/dL in low ITPase vs. ‐1.7 g/dL in high ITPase; NS). ITPase activity did not have a significant impact on platelet counts overall; however female subjects with lower ITPase activity had a significantly higher incidence of thrombocytosis (32.63 ×10⁹/L in low ITPase vs 1.46 ×10⁹/L in high ITPase; p=0.016). No association was noted between ITPase activity reduction and Hb levels or platelet counts in patients treated without ribavirin. Reduction in ITPase activity had no impact on virologic response to DAA treatment, viral kinetics, or baseline IP‐10 levels. Conclusions: Our study demonstrates that genetic variants in ITPA that associate with reduced activity may help predict anemia in chronic hepatitis C patients treated with IFN‐free regimens containing ribavirin. This may be particularly helpful in the contexts of subjects with difficult to treat HCV infection, such as patients with cirrhosis for who ribavirin‐containing regimens are recommended. In contrast to some of the studies that analyzed IFN‐containing regimens, our study showed no impact of ITPase activity reduction on treatment outcome or relapse rates in DAA‐based regimens.

Disclosures:

Manal Abunimeh ‐ Employment: AbbVie

Jonas Soderholm ‐ Employment: AbbVie

Justin W. Davis ‐ Employment: abbvie

Emily O. Dumas ‐ Employment: AbbVie; Stock Shareholder: AbbVie Daniel E. Cohen ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Jeffrey F. Waring ‐ Employment: AbbVie; Patent Held/Filed: AbbVie; Stock Shareholder: AbbVie

Martin Lagging ‐ Advisory Committees or Review Panels: MSD, AbbVie, Gilead, Medivir, BMS; Speaking and Teaching: MSD, AbbVie, Gilead, Medivir, BMS

The following people have nothing to disclose: Aparna Vasanthakumar

¹University of Pennsylvania Hospital, Philadelphia, PA; ²University of Miami Miller School of Medicine, Miami, FL; ³Karolinska Institute, Stockholm, Sweden; ⁴Merck & Co., Inc., Kenilworth, NJ

Decreased estimated glomerular filtration rate (eGFR) has been reported in patients with HCV infection receiving direct‐acting antiviral agents. EBR/GZR was safe and efficacious in patients with chronic kidney disease stage 4/5 (CKD 4/5) in the C‐SURFER study. The aim of this analysis was to evaluate the impact of EBR/GZR on eGFR in patients with less severe CKD. We analyzed a pooled dataset of 1689 patients who received EBR/GZR (50 mg/100 mg) with or without ribavirin (RBV) for 8 (n=91, 5%), 12 (n=1238, 73%), 16 (n=211, 12%), or 18 (n=149, 9%) weeks (656 patients [39%] received RBV). Patients were treatment‐naïve or treatment‐experienced, and included cirrhotics and those with HIV co‐infection. Creatinine values were assessed at baseline and ≥1 post‐baseline timepoint. eGFR was calculated using the Modified Diet in Renal Disease equation at baseline, end of treatment, and 12 weeks post‐therapy. Of the 1689 patients evaluated, 32 had CKD 3 (eGFR <60 mL/min/1.73 m² to ≥30 mL/min/1.73 m²) and 1657 had eGFR ≥60 mL/min/1.73 m² (Table). Demographics were similar in both groups except for a higher proportion of HIV‐co‐infected patients in the CKD 3 group (41% vs. 17%). Patients with CKD 3 and those with eGFR >60 mL/ min/1.73 m² at baseline did not show any decrease in eGFR during treatment or follow‐up. EBR/GZR did not affect eGFR in patients with pre‐existing eGFR ≥60 mL/min/1.73 m² or those with CKD3. Treatment duration, RBV co‐administration, cirrhosis, or HIV coinfection did not adversely affect renal outcome.

Patient Demographics and On‐Treatment Change in eGFR

Disclosures:

K. Rajender Reddy ‐ Advisory Committees or Review Panels: Merck, Janssen, BMS, Abbvie, Gilead; Grant/Research Support: Merck, BMS, Gilead, Janssen, Abbvie

David Roth ‐ Advisory Committees or Review Panels: Merck, Sharp and Dome; Consulting: Merck, Sharp and Dome

Peggy Hwang ‐ Employment: Merck, Merck Barbara Haber ‐ Employment: Merck & Co., Inc.

Bach‐Yen T. Nguyen ‐ Employment: Merck

Eliav Barr ‐ Employment: Merck; Stock Shareholder: Merck

Janice Wahl ‐ Employment: Merck & Co,

Wayne Greaves ‐ Employment: Merck

The following people have nothing to disclose: Annette Bruchfeld

¹Pharmacology, University of Liverpool, Liverpool, United Kingdom; ²FixHepC, GP2U Telehealth, Hobart, TAS, Australia; ³Hepatology, Nedlands Medical Centre, Nedlands, WA, Australia; ⁴Kingswood Pharmacy, Kingswood, NSW, Australia; ⁵University of Tasmania, Hobart, TAS, Australia; ⁶Faculty of Medicine, Imperial College, London, United Kingdom

Introduction: High prices of Direct Acting Antivirals (DAAs) can prevent access to treatment. Generic versions of sofosbuvir, daclatasvir and ledipasvir are being mass produced for prices under 1% of the current US retail price. Patients have the legal right to import 3 months of treatment into Australia, UK, New Zealand and many other countries provided it is for their personal use Worldwide, several thousand patients are being treated with legally imported Direct Acting Antivirals. There are Hepatitis C Buyers Clubs established in Russia, USA, Australia, SE Asia and the UK This analysis assessed the efficacy and safety of generic DAAs accessed via these personal importation rules, through the FixHepC Buyers Club. Methods: Sofosbuvir (SOF), ledipasvir (LDV) and daclatasvir (DCV) were imported from generic companies in India, China and Bangladesh Selection of DAAs and treatment duration depended on baseline HCV Genotype and fibrosis stage To provision patient safety, these generic DAAs were evaluated for quality using High Precision Liquid Chromatograhy (HPLC) and Nuclear Magnetic Resonance (NMR). Patients were evaluated pre‐treatment, during treatment and then for SVR 4 and 12. Adverse events were recorded. This analysis includes data from 481 patients from two clinics. Through the FixHepC Buyers Club, patients were treated in the USA, Europe, Australia, New Zealand and SE Asia. Summary SVR rates were compared with equivalent data from the original Phase 3 trials of SOF/LDV and SOF/DCV. Results: Of the 481 patients treated, 252 received SOF/LDV, 226 SOF/DCV and 3 SOF/ RBV. Overall, the patients were 55% male with a mean age of 55 years; 30% had cirrhosis; 65% were Genotype 1 and the aseline HCV RNA was 6.48 log10 lU/mL. During

the first four weeks of treatment, the viral decay kinetics of HCV RNA in the first weeks of treatment were similar to results from the original Phase 2 studies of SOF/DCV and SOF/LDV Based on currently available data, the percentage with HCV RNA <LLOQ was 320/322 (99.4%) at end of treatment (EOT), 141/152 (92.8%) at SVR 4 and 102/112 (91.1%) at SVR12. In Genotype 1 the SVR4 rates were 93.2% (69/74) with SOF/ LDV and 97.5% (39/40) with SOF/DCV. These SVR rates were consistent with results from the original trials of these DAA combinations. Conclusions: In this analysis, treatment with legally imported generic DAAs achieved overall SVR12 rates of 91.1% and these rates are comparable to those seen in Phase 3 trials of the branded treatments Mass treatment with the current generic DAAs is a feasible, low‐cost option where high prices prevent access to branded treatment.

Disclosures:

The following people have nothing to disclose: James A. Freeman, Richard Sallie, Adam Kennedy, Greg Jeffreys, Anna Savage, Andrew M. Hill

Molecular & Clinical Cancer Medicine, University of Liverpool, UK, Liverpool, United Kingdom; ²University of St. Andrews, St. Andrews, United Kingdom; ³Ogaki Municipal Hospital, Gifu, Japan

Purpose:. Among patients with chronic HCV, there is little information on the benefit of achieving SVR in terms of liver function in comparison to non‐responders. Here we assess liver function by the recently devised ALBI score¹. Methods: 1118 patients were followed‐up for a median 8.9 years (95% CI 8.5 ‐ 9.2) and classified as achieving SVR (59%), relapse (24%) or no response (NR 17%) having received interferon based therapy. Results. Differences in liver function in each group was evident by the end of treatment improving in all, but falling off rapidly in NR and relapse cohorts (figure). Survival was better in those with SVR (92% for SVR and 76% for non‐SVR respectively at 15 years, p<0.0001). Fibrosis, as assessed by the FIB‐4 index, progressed significantly in the R and NR groups. HCC was the major cause of death (47%), the great majority (90%) occurring among the non‐SVR group. Overall 5.4% from those who died (or 0.6% overall) were recorded as dying from liver failure. Conclusions. Within the timeframe of this study SVR is associated with improved liver function and less progression of fibrosis but any improvement in survival appears to be largely as a result of reduction in HCC development. Reference:¹ Johnson PJ et al., J. Clin. Oncol. 2014.

Changes in ALBI score according to treatment response. Lower scores on the vertical axis indicate better liver function

Disclosures:

The following people have nothing to disclose: Philip J. Johnson, Emily de Groot, Sarah Berhane, Toshifumi Tada, Takashi Kumada, Hidenori Toyoda

¹Duke University, Durham, NC; ²University Hospital Archet, Nice, France; ³NIH, Rockville, MD; ⁴University of Southern California, Los Angeles, CA; ⁵Gilead Sciences, Foster City, CA; ⁶Ottawa Hospital, Ottawa, ON, Canada; ⁷Mt Sinai School of Medicine, New York, NY; ⁸Johns Hopkins University, Baltimore, MD

BACKGROUND and AIMS: In clinical trials, SOF‐based regimens have performed similarly in patients with HIV/HCV co‐infection and HCV mono‐infection. Recent reports suggest HCV monoinfected patients achieve similar SVR rates with SOF‐ based regimens in real world cohorts (RWC) as those observed in clinical trials, however this has not yet been demonstrated in HIV/HCV co‐infected patients. The aim of this study was to compare the efficacy of the single tablet regimen of ledipasvir/ sofosbuvir (LDV/SOF) in HCV genotype 1 patients with HIV/ HCV co‐infection in clinical trials to the effectiveness in RWC. METHODS: In this analysis, data from three clinical trials of LDV/SOF in HIV/HCV co‐infected patients is compared to four RWC. RWC were selected based on willingness to participate and had at least 50 HIV/HCV co‐infected patients. The clinical trials include data from ERADICATE, ION‐4, and ANRS HC31 SOFTRIH study. The RWC include HCV‐TRIO, ASCEND, Portugal, and Veterans Affairs (USC) and represent diverse patient populations from Europe and U S including academic centers, urban primary care settings and the Veterans Health Administration Baseline characteristics and efficacy were analyzed. RESULTS: The clinical trials enrolled 445 patients with the following baseline characteristics: male (79%), black (40%), and cirrhosis (20%). The RWC studies enrolled 733 patients with the following overall baseline characteristics: male (79%), black (41%), and cirrhosis (30%) in those that reported demographics Patients enrolled in the clinical trials were treated with 12 or 24 weeks of LDV/SOF with an overall SVR12 rate of 97%. In the RWC, patients were treated with 8, 12, or 24 weeks of LDV/SOF ± RBV and the overall SVR12 was 95% The individual study results are presented in Table 1. CONCLUSIONS: Real world data in HIV/HCV co‐infected patients correlates closely with data seen in the clinical trials SVR rates were high across all populations including black race and treatment experienced patients with cirrhosis. This analysis demonstrates that SVR rates from RWC are generalizable from clinical trials.

Table 1. Clinical trials and RWC with LDV/SOF ± RBV in HIV/ HCV co‐infection

† 65 patients were evaluable for virological efficacy.

*Contains patients treated for 8 weeks.

Disclosures:

Susanna Naggie ‐ Advisory Committees or Review Panels: Merck; Grant/ Research Support: Tacere, Gilead, AbbVie, BMS, Jenssen, Merck

Eric Rosenthal ‐ Board Membership: gilead, msd, Abbvie

Justin McGinnis ‐ Consulting: Gilead; Grant/Research Support: AbbVie Sarjita Naik ‐ Employment: Gilead Sciences

Macky Natha ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Joseph Llewellyn ‐ Employment: Gilead Sciences Richard Haubrich ‐ Employment: Gilead

Anu O. Osinusi ‐ Employment: Gilead Sciences Inc; Stock Shareholder: Gilead Sciences Inc

Luisa M. Stamm ‐ Employment: Gilead Sciences

Curtis Cooper ‐ Advisory Committees or Review Panels: Gilead, Abbvie, MERCK; Grant/Research Support: MERCK, Gilead, Abbvie; Speaking and Teaching: MERCK, Abbvie, Gilead

Douglas T. Dieterich ‐ Advisory Committees or Review Panels: Gilead, BMS, Abbvie, Janssen, Merck, Achillion

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

The following people have nothing to disclose: Sarah Kattakuzhy

Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

OBJECTIVES: In Japan, dual oral therapy with daclatasvir (DCV) and asunaprevir (ASV) is the first interferon (IFN) ‐free therapy approved for patients with hepatitis C virus (HCV) genotype 1b infection in July 2014. Combination therapy with DCV and ASV has been primarily used in patients without NS5A L31 or Y93 resistance‐associated variants (RAVs) prior to treatment. In this study, we examined the characteristics of patients without baseline L31 or Y93 RAVs who failed to achieve HCV eradication with DCV+ASV therapy and identified new baseline NS5A RAVs that are closely associated with failure of combination therapy. METHODS: A total of 335 patients with HCV genotype 1b infection with no NS5A L31, NS5A Y93, or NS3 D168 RAVs prior to DCV+ASV therapy were enrolled. RAVs were evaluated using the direct sequence method. RESULTS: Patient age ranged from 34 to 86 years (median, 70), 216 patients (65%) were female, and 107 (32%) patients had cirrhosis. One hundred eighty patients (54%) had prior IFN‐based therapy, of whom 101 (56%) received pegylated‐IFN+ribavirin treatment. Sustained virologic response at 12 weeks (SVR12) was achieved in 297 patients (89%). The rate of SVR12 in patients with cirrhosis or HCV RNA ≥6.2 logIU/mL was lower than in patients with chronic hepatitis or HCV RNA <6.2 logIU/ mL (83% vs 91%, and 86% vs 92%, respectively). Patients with NS5A Q24, L28, and/or R30 RAVs had a significantly lower SVR12 rate compared with patients without these RAVs (67% vs 92%, p<0.001). The coexistence of NS5A F37 and Q54 RAVs was closely associated with treatment failure (with both RAVs, 80%; without both RAV, 92%, p=0.004). Although 43 patients had adverse events resulting in cessation of DCV+ASV therapy, all patients receiving DCV+ASV for more than six weeks, and those with ALT elevation, achieved SVR12. Multivariate analysis showed that NS5A Q24, L28, and/or R30 RAVs (odds ratios, 8.021; 95% confidence interval, 3.193‐20.150), coexistence of F37 and Q54 (4.429; 1.936–10.132), discontinuation of therapy as a result of adverse events (5.403;1.799–16.227), and grade 2 or higher ALT elevation (0.104; 0.012–0.913) were significantly associated with virologic failure. Pretreatment coexistence of NS5A Q24, L28, R30, F37, or Q54 RAVs was present in 28 of 29 (96.6%) patients with virologic failure. CONCLUSION: In patients without NS5A L31 or Y93 RAVs, the virological effect of DCV+ASV therapy was associated with baseline NS5A Q24, L28, and/or R30 RAVs and coexistence of F37 and Q54 RAVs. These results indicate that coexistence of baseline RAVs other than NS5A L31 and Y93 affects the antiviral effect of DCV+ASV therapy

Disclosures:

The following people have nothing to disclose: Seiichi Mawatari, Akihiro Moriuchi, Sho Ijuin, Haruka Sakae, Oki Taniyama, Kazuaki Tabu, Akihiko Oshige, Kohei Oda, Tsutomu Tamai, Akio Ido

¹Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany; ²Medizinische Hochschule Hannover, Hannover, Germany; ³ifi‐Institut für Interdisziplinäre Medizin, Hamburg, Germany; ⁴Gastroenterologische Gemeinschaftspraxis, Kiel, Germany; ⁵Universitätsklinikum Bonn, Bonn, Germany; ⁶Medizinisches Versorgungszentrum, Düsseldorf, Germany; ⁷Universitätsklinikum Tübingen, Tübingen, Germany

Background Treatment with direct antiviral agents (DAAs) achieved high sustained virologic response (SVR) rates across a broad range of patients with chronic hepatitis C virus (HCV) infection. Presence of baseline resistance‐associated variants (RAVs) has been associated with reduced SVR rates depending on the DAA regimen There are few data on retreatment after DAA failure. However, AASLD guidelines recommend a switch to another DAA drug class, the addition of ribavirin and treatment extension to 24 weeks In addition, testing for RAVs is recommended prior to initiating retreatment. Methods Patients with failure to currently approved DAA combination therapies were drawn from a large resistance database comprising more than 3900 patients. Post failure serum samples were analyzed for the presence of RAVs by direct sequencing of the NS3, NS5A and NS4B genes. Patients with urgent reasons were retreated based on the RAV analysis and guideline recommendations. Results In total, 456 patients with failure to different DAA combinations were analyzed All currently approved DAA therapies were affected by treatment failure These include ledipasvir/sofosbuvir ±ribavirin (RBV) (n=178), simeprevir/sofosbuvir ±RBV (n=63), daclatasvir/sofosbuvir ±RBV (n=70), sofosbuvir/RBV (n=93; genotypes 2/3 only), and paritaprevir/ombitasvir and dasabuvir ±RBV (3D; n=52). RAVs were detected in 90% of genotype (GT) 1 failures and 39% of patients with GT3, including 3 patients with the NS5B RAV S282T (GT1b: n=1; GT3: n=2). Retreatment was initiated in 73 (16%) of GT1/3 patients of whom 74% had cirrhosis. The majority of retreated patients had failed simeprevir/sofosbuvir. For retreatment, either ledipasvir/sofosbuvir or the 3D regimen were chosen. So far, 43 of GT1/ GT3 patients have completed follow‐up and 89% of these patients achieved SVR. Conclusion Retreatment was started in only a small subgroup of DAA failures, mainly due to the lack of approved regimens By using an individualized treatment approach based on post‐failure RAV analysis and switching to another regimen with a different DAA target, SVR can be achieved in the majority of DAA failures.

Disclosures:

Johannes Vermehren ‐ Advisory Committees or Review Panels: AbbVie, Abbott; Speaking and Teaching: AbbVie, Bristol‐Myers Squibb, Gilead, Medtronic

Joerg Petersen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead, Novartis, Merck, Bristol‐Myers Squibb, Gilead, Novartis, Merck; Grant/ Research Support: Roche, GlaxoSmithKline, Roche, GlaxoSmithKline; Speaking and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck

Holger Hinrichsen ‐ Advisory Committees or Review Panels: BMS, Janssen, Gilead, Abbvie; Speaking and Teaching: MSD

Stefan Mauss ‐ Advisory Committees or Review Panels: BMS, AbbVie, ViiV, Gilead; Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD Stefan Zeuzem ‐ Consulting: Abbvie, Bristol‐Myers Squibb Co., Gilead, Merck & Co., Janssen

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

The following people have nothing to disclose: Julia Dietz, Simone Susser, Thomas von Hahn, Ulrich Spengler, Christoph P. Berg

¹Victorian Liver Transplant Unit, Melbourne, VIC, Australia; ²Australian National Liver Transplant Unit, Sydney, NSW, Australia; ³Alfred Health, Melbourne, VIC, Australia; ⁴South Australian Liver Transplant Unit, Adelaide, SA, Australia; ⁵St Vincent's Hospital, Melbourne, VIC, Australia; ⁶Westmead Hospital, Sydney, NSW, Australia; ⁷Western Australian Liver Transplant Unit, Perth, WA, Australia; ⁸Queensland Liver Transplant Unit, Brisbane, QLD, Australia

Introduction: Antiviral therapy for hepatitis C (HCV) has the potential to improve liver function in patients with decompensated HCV cirrhosis who are candidates for liver transplant However, data on treatment outcomes in this population are limited. Methods: We prospectively collected data on all patients who satisfied the current minimum criterion for transplantation in decompensated cirrhosis in Australia (MELD ≥15) who commenced combination therapy with sofosbuvir and daclatasvir (sof/dac) with or without ribavirin (riba) for 24 weeks under the Australian Patient Supply Program (TOSCAR) and analysed outcomes including SVR12, death and transplant. Results: The study included 110 patients (M/F, 80/30; mean ± standard deviation (SD) age, 55.9 ± 7.7 years; mean ± SD Child Pugh Score (CPS), 10.0 ± 1.5) whom were followed for at least 36 weeks from commencement of treatment. Genotypes were predominantly 1 and 3.108 patients received sof/dac and two received sof/dac/riba. Forty‐three patients (39%) had failed previous therapy. Seventy‐eight patients completed 24 weeks of therapy, of whom three were transplanted during follow up. SVR12 was achieved in 60 patients (76.9%) (genotype 1 (n=34), SVR12=79.4%; genotype 2 (n=2), SVR12 = 100%; genotype 3 (n=38), SVR12 = 63.2%; genotype 4 (n=4), SVR12 = 100%), while 17 patients relapsed (21.8%) and one patient was lost to follow up Thirty‐two patients failed to complete therapy due to death (n=11, 10%), transplant (n=18, 16%) or adverse events (n=3, 3%). Overall, the mean MELD and CP scores of the 110 patients in the study fell from 17.0 to 15.7 (p=0.03) and 10.0 to 8.5 (p<0.01), respectively from baseline. In those patients who completed treatment, mean MELD and CPS fell from 16.8 to 14.3 (p<0.01) and 9.7 to 8.1 (p<0.01), respectively. In those who died or were transplanted (due to liver failure), mean MELD increased from 18.0 to 21.0 at death or transplant (p=0.045) while mean CPS remained unchanged (10.7 to l0.3, p=0.27). Overall, 59 (76%) patients achieved an improvement in both MELD and CP scores with treatment. In patients with MELD ≥ 20 at entry (n=16), 69% died or required rescue liver transplantation whilst on treatment compared to 16% in patients with MELD < 20 (p<0.0001). Conclusions: SVR12 rates in HCV positive patients with advanced liver disease treated with sofosbuvir and daclatasvir (with/without ribavirin) are reduced compared to other patient groups. Although treatment improves MELD and CP scores in most patients, a significant proportion will die or require rescue transplantation and in those with MELD ≥ 20 it may be better to delay treatment until the post‐transplant period.

Disclosures:

Geoff McCaughan ‐ Advisory Committees or Review Panels: Gilead, ABBVIE Stuart K. Roberts ‐ Board Membership: AbbVie, Gilead

Simone I. Strasser ‐ Advisory Committees or Review Panels: AbbVie, MSD, Bristol‐Myers Squibb, Gilead, Norgine, Bayer Healthcare; Speaking and Teaching: Roche Products Australia, Bayer Healthcare, Bristol‐Myers Squibb, MSD, Gilead, Abbvie

Caroline Tallis ‐ Advisory Committees or Review Panels: BMS; Speaking and Teaching: Gilead

Jacob George ‐ Advisory Committees or Review Panels: Pharmaxis, BMS, MSD, Gilead, Janssen, Abbvie; Grant/Research Support: MSD

Alex J. Thompson ‐ Advisory Committees or Review Panels: Gilead, Abbvie, BMS, Merck, Spring Bank Pharmaceuticals, Arrowhead, Roche; Grant/Research Support: Gilead, Abbvie, BMS, Merck; Speaking and Teaching: Roche, Gilead, Abbvie, BMS

Susan Mason ‐ Advisory Committees or Review Panels: Janssen, MSD, BMS, Gilead Sciences; Grant/Research Support: Janssen, MSD; Speaking and Teaching: ASHM

Brenda Morales ‐ Advisory Committees or Review Panels: MSD, Jansen, Roche, Abbvie, BMS

Peter W. Angus ‐ Advisory Committees or Review Panels: Gilead Sciences, BMS, Bayer; Grant/Research Support: Gilead sciences

The following people have nothing to disclose: Phoebe A. Thwaites, Paul Gow, Alan J. Wigg, Gary P. Jeffrey, Joanne Mitchell

¹Internal Medicine III, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; ²Internal Medicine IV, Gastroenterology and Hepatology, Wilhelminenspital, Vienna, Austria; ³Internal Medicine IV, Elisabethinen Krankenhaus Linz, Linz, Austria; ⁴Internal Medicine II, Medical University Innsbruck, Innsbruck, Austria; ⁵Internal Medicine, Medical University of Graz, Graz, Austria; ⁶4th Med. Dpt. of Infectious Diseases and Tropical Medicine, Kaiser Franz Joseph Spital, Vienna, Austria; ⁷Internal Medicine I, Paracelsus Medical University, Salzburg, Austria; ⁸Department for Internal Medicine, Landeskrankenhaus Hall in Tirol, Hall in Tirol, Austria

Background and aims: Interferon (IFN)‐free antiviral treatment with DAAs is very effective to cure HCV infection, but the long‐term outcome of patients is unknown. AURIC (Austrian Ribavirin [RBV]/Interferon free Cohort; ClinicalTrials. gov, NCT02628717) is a “real world” study including patients with advanced liver disease (F3/F4) without evidence of hepatocellular carcinoma (HCC) treated with IFN/RBV free DAA combinations. In this study patients' outcomes were evaluated after at least 48 weeks of treatment free follow up Methods: Of the 484 patients in AURIC 456 (94.2%) had a sustained virological response after 12 weeks (SVR12) of follow up, 20 relapsed (4.1%) and 8 were lost to follow up. At the time of abstract submission, 191 SVR12 patients completed at least 48 weeks of treatment free follow up (m/f=112/79; mean age 57.8± 10.4yrs; genotype [GT]‐1:170, GT‐3:7; GT‐4:14; F3:41 F4:150; Child Pugh Score[CPS] A:117, B:27, C:6; treatment: sofosbuvir[SOF]+daclatasvir[DCV]:85, DCV+sime‐ previr[SMV]:83, SOF+ledipasvir: 19, SMV+DCV: 1, 3D:3). Results: SVR was durable during follow up. CPS improved in 22 patients (CPS‐B to A: 19, C to A:1, C to B: 2) and worsened in 6 (A to B: 3, A to C:1 B to C: 2). Eleven patients (5.5%) had liver related events: 7 ascites, 3 hepatic encephalopathy and one had a variceal hemorrhage. Five patients were transplanted after end of therapy (EoT) due to decompensated liver cirrhosis or occurrence of a de novo HCC, one them died due to thrombotic complications. Three patients were delisted due to clinical improvement. Seven additional patients died: five related to liver disease, three due to nonhepatic diseases. As reported previously, HCC was diagnosed in 13 (6.8%) patients during follow‐up (m/f=9/4, mean age 65.4±6.5yrs, GT‐1:12; GT‐4:1; CPS at baseline:A:7, B:3, C:1, F3:2). Overall, platelet count (plts) and serum albumin (alb) improved from baseline (BL) to EoT, and furthermore from EoT to FUP48 (plts: BL: 133 vs. EoT:142G/L, vs. SVR 48: 152G/L; alb: 39.4 vs. 41.0 g/L, vs. 42.7g/L, all: p<0.005). Conclusion: Clinical condition and laboratory markers of liver function improved in most patients with cirrhosis after successful DAA therapy; however morbidity and mortality rate remains substantial. Furthermore, an unexpectedly high rate of HCC was observed shortly after EoT implicating the need of vigorous surveillance after achieving SVR in patients with cirrhosis.

Disclosures:

Rudolf E. Stauber ‐ Advisory Committees or Review Panels: Gilead, MSD, BMS; Grant/Research Support: AbbVie

Hermann Laferl ‐ Advisory Committees or Review Panels: Janssen; Grant/ Research Support: Gilead, AbbVie, Roche; Speaking and Teaching: Gilead

Andreas Maieron ‐ Advisory Committees or Review Panels: MSD, Jannsen, BMS, B√∂hringer Ingelheim, Gilead, Abbvie ; Grant/Research Support: Roche; Speaking and Teaching: Roche, MSD, Jannsen, Gilead, Abbvie

Markus Peck‐Radosavljevic ‐ Advisory Committees or Review Panels: Bayer, Intercept, Gilead, Janssen, BMS, AbbVie; Consulting: Bayer, Shionogi, Boehringer‐Ingelheim, ONO Pharma, Eli Lilly, AbbVie; Grant/Research Support: Bayer, Gilead, MSD, AbbVie; Speaking and Teaching: Bayer, Gilead, MSD, AbbVie

Ivo Graziadei ‐ Advisory Committees or Review Panels: Gilead, AbbVie, MSD, Janssen, BMS; Speaking and Teaching: Gilead, AbbVie, MSD, BMS

Michael H. Trauner ‐ Consulting: Albireo, Falk, Phenex, Gilead, Novartis, MSD; Grant/Research Support: Falk, Albireo, Intercept

Harald Hofer ‐ Advisory Committees or Review Panels: Gilead, Abbvie; Speaking and Teaching: Janssen, BMS, Gilead, Abbvie

Peter Ferenci ‐ Advisory Committees or Review Panels: Idenix, Gilead, MSD, Janssen, Salix, AbbVie, BMS, Wilson Therapeutics; Patent Held/Filed: Madaus Rottapharm; Speaking and Teaching: Gilead, Roche

The following people have nothing to disclose: Karin Kozbial, Stephan Moser, Remy Schwarzer, Ramona Al Zoairy, Heinz M. Zoller, Sandra Beinhardt, Albert Stattermayer, Rafael Stern, Petra E. Steindl‐Munda, Michael P. Strasser

¹Cattedra ed U.O.C. di Gastroenterologia ed Epatologia, Palermo, Italy; ²Clinic of Gastroenterology and Hepatology, Université Politecnica delle Marche, Ancona, Italy, Ancona, Italy; ³Italian Medicines Agency, Roma, Italy; ⁴UO Gastroenterologia ed Epatologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Italy, Milan, Italy; ⁵Department of Molecular Medicine, University of Padova, Padova, Italy, Padova, Italy; ⁶Centro per le malattie del Fegato‐ Ospedale Fatebenefratelli ‐ Napoli, Italy, Napoli, Italy; ⁷National Institute for Infectious Diseases “Lazzaro Spallanzani” IRCCS, Roma, Italy., Roma, Italy; ⁸Dipartimento Malattie infettive ‐ Fondazione IRCCS Policlinico San Matteo Pavia Italia ‐ Université degli studi di Pavia, Italy, Pavia, Italy; ⁹Humanitas University and Humanitas Research Hospital Rozzano, Milano, Milano, Italy; ¹⁰U.O.C. Infezioni sistemiche e dell'immunodepresso. A.O. Ospedali dei Colli Napoli, Italy, Napoli, Italy; ¹¹Infectious Diseases and Viral Hepatitis, Second University of Naples, Italy, Napoli, Italy; ¹²Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy, Genova, Italy; ¹³Gastroenterology Department of Clinical Medicine, Sapienza University of Rome, Italy, Roma, Italy; ¹⁴Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy, Caserta, Italy; ¹⁵Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Italy, Roma, Italy; ¹⁶Department of Infectious Diseases, AO Niguarda Ca' Granda, Milano, Italy, Milano, Italy; ¹⁷Division of Clinical and Molecular Hepatology, Department of Clinical and Experimental Medicine, University Hospital of Messina, Italy, Messina, Italy; ¹⁸Gastroenterology and digestive Endoscopy, University Hospital Policlinico Bari, Italy, Bari, Italy; ¹⁹Division of Gastroenterology, Azienda Ospedaliero‐Universitaria Policlinico di Modena, Italy Université degli Studi di Modena e Reggio Emilia, Via del Pozzo 71, 41124 Modena, Italy, Modena, Italy; ²⁰Anna Linda Zignego, Interdepartmental Centre MASVE, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, Firenze, Italy

Background Compassionate‐use programs for direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection provide access to DAAs pending approval and provide real‐world data on the effectiveness and safety of these regimens. We collected data from a compassionate‐use nationwide program (promoted by the Italian Medicines Agency) to provide access to the 3‐DAA regimen of ombitasvir, paritaprevir, with the pharmacokinetic enhancer ritonavir, and dasabuvir (OBV/PTV/r + DSV), with ribavirin (RBV) for GT1 infection and the 2‐DAA regimen of OBV/PTV/r + RBV for GT4 infection in patients with cirrhosis at high risk of decompensation. Methods HCV GT1‐infected patients with cirrhosis at high risk of decompensation received once‐daily co‐formulated OBV/PTV/r (25/150/100 mg) and twice‐daily dasabuvir (250 mg) for 12 (GT1b) or 24 (GT1a) weeks; GT4‐infected patients received co‐formulated OBV/pTV/r (25/150/100 mg) for 24 weeks. The primary efficacy endpoint was sustained virologic response at week 12 post‐treatment. Univariate and multivariate logistic regression were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Results The overall SVR12 rate was 95.5% (728/762) among cirrhotic patients who received OBV/PTV/r ± DSV + RBV therapy for 12 or 24 weeks. Logistic regression analyses identified that bilirubin <2 mg/d (OR: 4.76; 95% CI: 1.83‐12.3; p=0.001) and marginally albumin ≥3.5 g/dL (OR: 2.36; 95% CI: 0.96‐6.16; p=0.07) were associated with SVR12. 3.4% of patients discontinued treatment due to adverse events. Conclusions Our findings suggest that the safety and effectiveness of OBV/PTV/r ± DSV + RBV in real‐life use in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation are similar to those reported in clinical trials.

Disclosures:

Alessio Aghemo ‐ Advisory Committees or Review Panels: Abbvie, Gilead; Grant/Research Support: Gilead; Speaking and Teaching: Abbvie, Gilead, MSD, Janssen, BMS

Alfredo Alberti ‐ Advisory Committees or Review Panels: Merck, roche, Gilead, Merck, roche, Gilead, Merck, roche, Gilead, Merck, roche, Gilead, Abbvie, Janssen; Grant/Research Support: Merck, gilead, Merck, gilead, Merck, gilead, Merck, gilead, Abbvie, Janssen; Speaking and Teaching: novartis, BMS, novartis, BMS, novartis, BMS, novartis, BMS

Andrea Antinori ‐ Consulting: Bristol Myers Squibb, Gilead, Merck, Janssen‐Cilag, Abbie, ViiV; Grant/Research Support: Gilead, Bristol Myers Squibb, Janssen‐Cilag, ViiV

Giovanni B. Gaeta ‐ Advisory Committees or Review Panels: Janssen, Merck, Abbvie, Roche; Speaking and Teaching: BMS, Gilead, merck

Edoardo G. Giannini ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Gilead; Consulting: 4‐SC; Grant/Research Support: GlaxoSmithKline, 4‐SC; Speaking and Teaching: GlaxoSmithKline, MSD, Roche, Gilead, Bayer, BMS, Janssen, Novartis

Massimo Puoti ‐ Advisory Committees or Review Panels: GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis, GSK, Abbott, Janssen, MSD, Roche, Gilead Sciences, Novartis; Speaking and Teaching: BMS, BMS, BMS, BMS

Giovanni Raimondo ‐ Speaking and Teaching: BMS, Gilead, Roche, Merck, Janssen, Bayer, MSD

Francesca Ceccherini‐Silberstein ‐ Speaking and Teaching: Merck Sharp & Dohme, Gilead, Janssen, Abbvie, ViiV, Roche diagnosticis, BMS

Erica Villa ‐ Advisory Committees or Review Panels: MSD, Abbvie, GSK, Gilead; Speaking and Teaching: Novartis

The following people have nothing to disclose: Salvatore Petta, Marco Marzioni, Pierluigi Russo, Antonio Ascione, Raffaele Bruno, Savino Bruno, Antonio Chirianni, Manuela Merli, Vincenzo Messina, Simona Montilla, Carlo F Perno, Maria Rendina, Anna Linda Zignego, Luca Pani, Antonio Craxì

¹ Department of Hepatologie, Institut Arnault Tzanck, Saint‐Laurent‐du‐Var, France; ²Laboratoire Alphabio, Marseille, France; ³Hôpital Saint‐Joseph, Marseille, France; ⁴Hôpital d'Hyères, Hyères, France; ⁵Private Practice, Orange, France; ⁶Clinique du Palais, Grasse, France; ⁷Private Practice, Bourgoin‐Jallieu, France; ⁸Private Practice, Nîmes, France; ⁹Private Practice, Toulouse, France; ¹⁰Private Practice, Lyon, France; ¹¹Private Practice, Nanterre, France; ¹²Private Practice, Montpellier, France; ¹³Hôpital Européen, Marseille, France

Introduction: Retreatment options in experienced patients to new Direct Acting Antivirals (DAA) are not yet well defined. The aim of this study was to analyze the retreatment of patient who failed to a first course of regimen containing new DDA Patients & Methods: Two cohorts of patients treated with new DAA in real life for HCV infection (AVDLIB 1:186 patients and AVDLIB 2: 190 patients) were constituted since January 2014 to September 2015. Overall 376 patients were exposed to sofosbuvir (SOF) containing regimen (SOF+ Ribavirin (RBV), SOF+PE‐ GIFN +RBV, SOF +Simeprevir (SIM) ± RBV, SOF+Daclatasvir (DAC) ± RBV, SOF+ Ledipasvir (LDV) ± RBV) and 20 exposed to Viekirax± Exviera regimen. Results: Among these 376 patents, 20 (5%) relapsed (16 in AVDLIB1 and 4 in AVDLIB2 IFN free regimen). There were 18 males; fibrosis stage was F3 in 2 patients and F4 in 18 patients; HCV genotype repartition G1/ G2/G3/G4 was12/3/3/2, respectively. All relapsers but one received a second course of DDA recorded in 18/19 patients. The treatment of relapsers was as follow: one patient received a Viekirax+RBV 12 weeks course after SOF /PEGINF/RBV failure, 12 patients received SOF+DAC+RBV mostly during 24 weeks after SOF+PEGIFN+RBV n=8 and SOF+RBV n=4 failures, 2 patients received SOF+LED during 12 weeks after SOF+RBV and SOF+PEG+RBV failures, 2 patients received SOF+SIM +RBV during 24 weeks after SOF/PEG/RBV and SOF+LED failure and one patient received SOF+Elbasvir+Grazoprevir+RBV during 16 weeks after SOF+LED failure. NS5A RAVs with high level of cross‐resistance among NS5A inhibitors were found at the time of viral failure in two patients. SVR 12 was available in 14/18 patients and all of them achieved SVR 12. The results of the 4 remaining patients will be available at the time of the meeting Conclusion: This study showed that retreatment of patients who previously failed to DAA first course therapy is highly efficient: a SVR of 100% was observed in patients retreated with SOF or Viekirax based‐therapy, and for whom a post‐treatment follow‐up of at least 12 weeks is available. Second line DAA therapy, ideally with no cross‐resistance with the DAAs already administered, should be the solution to cure all HCV infected patients.

Disclosures:

Bertrand Hanslik ‐ Board Membership: MSD, Janssen, Mayoli, Gilead, Intercept; Speaking and Teaching: Roche, Aptalis, BMS, Echosens

Marc Bourlière ‐ Advisory Committees or Review Panels: Schering‐Plough, Bohringer inghelmein, Schering‐Plough, Bohringer inghelmein, Transgene; Board Membership: Bristol‐Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis, Tibotec, Abott, glaxo smith kline, Merck, Bristol‐Myers Squibb, Novartis, Tibotec, Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol‐Myers Squibb

The following people have nothing to disclose: Denis Ouzan, Guillaume Pénaranda, Gaelle Le Folgoc, Christophe Renou, Michel Antoni, Patrick Delasalle, Thierry Fontanges, Patricia Cerdan, Pierre Toulemonde, Sylvain Beorchia, Nathalie Boyer, Philippe Halfon

¹Gilead Sciences, Inc, Foster City, CA; ²Medizinische Klinik 1, Universitatsklinikum Frankfurt, Frankfurt, Germany; ³Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN; ⁴Toronto Center for Liver Disease, University Health Network, Toronto, ON, Canada; ⁵Johns Hopkins University, Boston, MA; ⁶Queen Mary University, London, United Kingdom; ⁷Mt. Sinai Beth Israel Hospital, New York, NY

Background: Normalization of ALT levels coincides with virologic suppression in most HCV‐infected patients treated with DAAs. The aim of this analysis was to characterize baseline (BL) factors of patients with persistently elevated ALT at the end of treatment (EOT). Methods: Patients from safety analysis sets of the LDV/SOF±RBV Phase 3 ION 1‐3 trials and SOF/ VEL ASTRAL1‐3 trials (n=3394) were included in this analysis if they were treated for at least 8 weeks and had both BL and EOT data available Elevated ALT was defined as ALT greater than upper limit of normal (ULN) as defined by the central laboratory. Results: Overall, 73% (2487/3394) of patients had received at least 8 weeks of treatment and had elevated ALT at BL. The majority had ALT normalization after initiation of LDV/ SOF±RBV or SOF/VEL, but 8% (200/2487) had elevated ALT at EOT. Compared to patients with ALT normalization, patients who continued to have elevated ALT at EOT had higher rates of cirrhosis and the co‐morbid conditions cholelithiasis, hepatic steatosis, diabetes mellitus, or hypertension; were more likely to be taking β blocking agents or diabetes medications; and had higher BMI and hemoglobin A1c values at baseline. A multivariate regression analysis will be presented, as well as analyses using AASLD thresholds for ALT values. Efficacy was similar between groups with nearly all patients with elevated BL ALT reaching HCV RNA < LLOQ by Week 4 of treatment. SVR12 was achieved in 96% (2193/2287) of patients with ALT normalization and 97% (193/200) for patients with elevated ALT at EOT. Conclusions LDV/SOF and SOF/VEL were highly efficacious in patients with elevated ALT at BL, regardless of whether ALT normalized by EOT. Patients with elevated ALT levels prior to HCV treatment, who do not have rapid and sustained normalization of transaminases, should be evaluated for other hepatobiliary or metabolic conditions that may contribute to liver inflammation which does not resolve with viral suppression.

Baseline Characteristics of Patients with Elevated Baseline ALT Treated with LDV/SOF or SOF/VEL

Disclosures:

Tania M. Welzel ‐ Advisory Committees or Review Panels: Novartis, Janssen, Gilead, Abbvie, Boehringer‐Ingelheim+, BMS

Paul Y. Kwo ‐ Advisory Committees or Review Panels: Abbott, Abbvie, BMS, Gilead, Janssen, Merck, Alnylam, Quest, CVS, Innovio; Grant/Research Support: Abbvie, BMS, Gilead, Merck, Janssen, Esai, Cepheid, Conatus

Ira M. Jacobson ‐ Consulting: AbbVie, Achillion, Bristol Myers Squibb, Intercept, Gilead, Janssen, Merck, Trek; Grant/Research Support: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck; Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen

Shampa De‐Oertel ‐ Employment: Gilead Sciences, Inc; Stock Shareholder: Gilead Sciences, Inc

John McNally ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

John G. McHutchison ‐ Employment: gilead; Stock Shareholder: gilead

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Graham R. Foster ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS, Alnylam; Board Membership: Boehringer Ingelheim; Grant/Research Support: Roche, Chughai, Springbank; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen

The following people have nothing to disclose: Jie Zhang, Keyur Patel

Southern California Research Center, Coronado, CA

BACKGROUND: HCV genotype 3 is still the challenging genotype. With current standard therapy the relapse rates are still considered high, particularly in patients with cirrhosis. The combination of Daclatasvir and Sofosbuvir with or without Ribavirin for 12 or 16 weeks have shown slightly improved SVR rates and lower relapse rates using weight‐based dosing of Ribavirin. The goal of our study is to explore the efficacy of 16 weeks versus 24 weeks of Daclatasvir/Sofosbuvir/Ribavi‐ rin in cirrhotic patients with HCV genotype 3, and to explore the importance of the initial Ribavirin dosing. METHODS: 49 subjects were screened into the study. 39 were randomized into two arms (16 weeks versus 24 weeks) in 1:1 ratio using IVRS. Baseline demographics and viral parameters were similar in both arms. The mean age was 55.4 ± 7 years; 22 males; 21 non‐Hispanics. 28 patients were treatment naive and 11 patients were experienced to Peg/RBV therapy. Cirrhosis was confirmed in all patients by Fibroscan. RESULTS: 39 patients were randomized into the study, and 32 patients completed the course of therapy 7 patients are still on treatment 100% of the patients who completed therapy achieved EOT viral negativity. In the 16‐week group, SVR¹² was 91.6% with only one patient relapse. This patient had over 90% adherence to the medication regimen and was recieving 1200 mg/ day RIbvirian. SVR¹² in the 24‐week group was 100% in the patients who finished the study (17/17). Ribavirin dose started at 800 mg/day in 25 patients and 1000‐1200 mg/day in 14 patients. Three patients in each group required a decrease in their Ribavirin dose due to anemia The starting dose of Ribavirin did not impact the SVR¹²CONCLUSION: The combination of Daclatasvir/Sofosbuvir/Ribavirin is recommended for HCV genotype 3 patients In cirrhotic patients our study shows 1) 16‐week treatment achieved 91.6% SVR¹² with only one relapse; 2) 24‐week treatment achieved 100% SVR¹²; 3) there was no significant difference in SVR between the two arms; 4) 800 mg/day of Ribavirin achieved the same viral response as weight‐based Ribavirin; 5) 16‐ and 24‐week treatment was well tolerated in patients with cirrhosis

Disclosures:

Tarek I. Hassanein ‐ Advisory Committees or Review Panels: AbbVie Pharmaceuticals, Bristol‐Myers Squibb, Trek Therapeutics; Grant/Research Support: AbbVie Pharmaceuticals, Obalon, Bristol‐Myers Squibb, Eiasi Pharmaceuticals, Gilead Sciences, Merck Sharp & Dohme, NGM BioPharmaceuticals, Ocera Therapeutics, Salix Pharmaceuticals, Sundise, TaiGen Biotechnology, Vital Therapies, Tobria, Shinoghi & Co. Ltd, La Jolla Pharmaceuticals, Trek Therapeutics, Novo Nordisk, Intercept; Speaking and Teaching: Baxter, Bristol‐Myers Squibb, Gilead Sciences, Salix Pharmaceuticals, AbbVie Pharmaceuticals

The following people have nothing to disclose: Yasmeen Esshaki, Catherine Hill, Renee Pozza, Jennifer Higham, B K. Luvisa, Anna Marie Hefner

¹St. Joseph's Hospital and Medical Center, Phoenix, AZ; ²Divison of Infectious Disease, Cherokee Nation W.W. Hastings Hospital, Tahlequah, OK; ³Division of Infectious Diseases, University of New Mexico, Albuquerque, NM; ⁴Division of Gastroenterology, University of Utah, Salt Lake City, UT; ⁵Infectious Diseases, University of Washington, Seattle, WA

Introduction: One quarter of HCV infected patients in the U.S. are not served by mainstream healthcare systems, including Native Americans, the incarcerated, and the homeless. Data on the efficacy of DAA therapies in these vulnerable populations is limited. Our aim was to determine the efficacy of DAA therapies and predictors of treatment response among Native Americans infected with chronic HCV. Methods: All Native American patients with chronic HCV treated at a specialty clinic or by primary care clinicians through the ECHO (Extension for Community Healthcare Outcomes) (ECHO) model who completed treatment with directly acting antiviral (DAA) therapies from 11/4/2011‐9/30/2015 were identified. Data on demographics, baseline laboratory values, treatment regimen, genotype, and viral load were systematically abstracted into a standardized database. In 191 patients (86%), data on psychiatric disease, HCV risk factors, and concomitant nonalcoholic fatty liver disease (NAFLD) was also collected. Results: 222 Native American patients were included and eligible for analysis. The majority of patients (n=163, 73%) were infected with HCV genotype 1; genotype 1a was the most common subtype (n=137, 62%), while genotype 2 and 3 represented 16% (n=26) and 10% (n=23) of the cohort 37% (n=83) of patients had cirrhosis Treatment regimens included sofosbuvir (SOF)/ledipasvir (LDV) (n=137), SOF/ribavirin (RBV) (n=63), simeprevir (SIM)/SOF (n=6), SIM/SOF/RBV (n=5), SOF/ pegylated‐interferon (PEG)/RBV (n=5), SOF/LDV/RBV (n=4), and paritaprevir/ritonavir/ombitasvir/dasabuvir ± RBV (n=2). Among patients with data, 35% (n=67) were actively using marijuana, opiates, benzodiazepines, amphetamines, and barbiturates and 26% (n=49) were diagnosed with nonalcoholic fatty liver disease (NAFLD). Overall, 84% (n=187) of patients achieved SVR12. When all missing patients (n=16) were excluded, SVR12 increased to 91%. Among the missing patients, 46% were active drug users, 69% had psychiatric disease, and 46% had cirrhosis Nineteen patients (9%) relapsed; of whom, 8 (42%) were cirrhotic and 16% (n=3) were previously treated. SVR12 was similar in cirrhotic (83%) vs. non‐cirrhotic patients (85%), active drug users (82%) vs. non/former users (87%), and concomitant NAFLD, HCV (90%) vs. non‐NA‐ FLD, HCV patients (84%). Conclusions: Overall, there was a high cure rate of HCV in Native Americans being treated with DAA regimens. Patients with cirrhosis, concomitant NAFLD, and even active drug use, all achieved high rates of SVR12. Given the efficacy of DAA treatment in this vulnerable, understudied population, more steps need to be taken to increase treatment availability.

Disclosures:

Jorge Mera ‐ Advisory Committees or Review Panels: gilead; Board Membership: CDC/HRSA; Grant/Research Support: AIDS AND EDUCATION TRAINING CENTER, Indian Health Services, Oklahoma University Health Science Center

Terry D. Box ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Salix, BMS; Grant/Research Support: Gilead, Merck, Intercept, BMS, AbbVie, Salix, Boehringer Ingelheim, ikaria; Speaking and Teaching: Gilead, Merck, AbbVie, Intercept, Salix

John D. Scott ‐ Advisory Committees or Review Panels: Tacere Therapeutics; Grant/Research Support: Merck

Robert Gish ‐ Advisory Committees or Review Panels: Gilead, AbbVie, Arrowhead, lonis, MERCK; Consulting: Eiger, Genentech, MERCK; Speaking and Teaching: Gilead, AbbVie, MERCk; Stock Shareholder: Arrowhead

Richard Manch ‐ Speaking and Teaching: Gilead, Abbvie, Merck, BMS, Salix, Bayer, Intercept

Anita Kohli ‐ Advisory Committees or Review Panels: Gilead, Alexion; Speaking and Teaching: Merck

The following people have nothing to disclose: Kartik Joshi, Karla A. Thornton, Paulina Deming, Miranda L. Sedillo, Crystal David, Whitney Essex, Jennifer Shade

¹Division of Infectious Diseases, Weill Cornell Medical College, Mars, PA; ²VA Pittsburgh Healthcare System, Pittsburgh, PA; ³University of Cincinnatti, Cincinnatti, OH

Background: DAA regimens have been associated with hepatic decompensation (HD), especially in patients with pre‐treatment cirrhosis, but large scale studies are not available to quantify the risk. Methods: In the ERCHIVES database, we analyzed those treated with a Paritaprevir/ritonavir, Ombitasvir, Dasabuvir (PrOD) regimen for hepatic decompensation (HD), and worsening renal function and compared them with those who received sofosbuvir/simeprevir (SOF/SIM) or sofosbuvir/ ledipasvir (SOF/LDV)regimen. Participants were followed up to 12 weeks post‐treatment. We excluded those with HIV, HBsAg+ and pre‐existing diagnosis of HD and hepatocellular carcinoma Results: Of 3,728 persons on PrOD, 1,578 on SOF/SIM and 10,440 on SOF/LDV, cirrhosis was present at baseline in 23%, 45% and 26% respectively. There were 15 HD events in the PrOD, 24 in the SOF/SIM and 52 in the SOF/LDV group. Incidence rates [95% CI] of HD/1,000 treatments initiated were 10.6[5.89,17.36] for the PrOD group, 32.4[20.74,48.16] for the SOF/SIM group and 13.0[9.74,17.10] for the SOF/LDV group Among those with baseline cirrhosis, these rates were 36.9[19.1,64.5], 61.8[38.2,94.5] and 41.1 [29.9,55.2] respectively, while among those without cirrhosis at baseline, these rates were 2.7[0.6,8.0], 7.5[1.5,21.8] and 2.7[1.2,5.4] respectively Advanced fibrosis was associated with increased risk of HD in all groups There were no deaths Proportion of persons with eGFR increase >30ml/min/1.73m² was higher among the PrOD group, but presence of cirrhosis did not appear to affect this. Conclusions: The overall incidence of HD in persons treated with PrOD regimen, on treatment and up to 12 weeks after completion of treatment, was comparable to those treated with SOF/LDV regimen, and was lower than among those treated with a SOF/SIM regimen Such risk was predominantly observed in those with cirrhosis at baseline.

Disclosures:

Adeel A. Butt‐Grant/Research Support: Gilead, AbbVie

Kristen M. Marks‐Grant/Research Support: Merck, Gilead

Obaid S. Shaikh ‐ Grant/Research Support: Gilead Sciences, Shinongi Pharmaceuticals,Merritt; Speaking and Teaching: Simply Speaking

Kenneth E. Sherman ‐ Advisory Committees or Review Panels: Janssen, Merck,Synteract; Grant/Research Support: MedImmune, Inovio, Merck, Gilead, Briston‐Myers Squibb

The following people have nothing to disclose: Yanjie Ren

¹Gastroenterology,Hepatology and Endocrinology, Hannover Medical School, Hannover,Germany; ²ifi‐institute for interdisciplinary medicine, Hamburg,Germany; ³Center of Hepatology, Göttingen, Germany;4Center for HIV and Hepatogastroenterology, Duesseldorf, Germany;⁵Center of Hepatology, Hannover, Germany; ⁶MVZ‐Offenburg,Offenburg, Germany; ⁷Center for interdisciplinary Medicine(CIM), Muenster, Germany; ⁸Center of Hepatology, Bottrop, Germany;⁹e.factum GmbH, Butzbach, Germany; ¹⁰J. W. Goethe‐University Hospital, Frankfurt, Germany; ¹¹Center of Gastroenterology,Herne, Germany; ¹²Department of Hepatology, University Hospital Leipzig, Leipzig, Germany; ¹³St. Josef‐Hospital, Katholisches Klinikum Oberhausen, Oberhausen, Germany; ¹⁴Leberstiftungs‐GmbH Deutschland, Hannover, Germany

Introduction: Treatment of HCV genotype 3 (GT3) is still more challenging compared to HCV genotype 1. Sustained virological response (SVR) rates for GT3 with the first approved IFN free regimen sofosbuvir (SOF)+ribavirin (RBV) are not satisfactory in patients with cirrhosis. Further treatment options include pegylated interferon (PegIFN)+SOF+RBV for 12 weeks, SOF+ledipasvir (LDV) or SOF+daclatasvir (DCV)±RBV for 12‐24 weeks. Data from large cohorts and the real‐world are still limited. Methods: The DHC‐R (Deutsches Hepatitis C‐Register, German Hepatitis C‐Registry) is a national multicenter real‐world cohort including >9,300 patients. Patients are treated at the discretion of the physician. Data are collected by a web‐based system. Data quality is analyzed by plausibility checks and on‐site monitoring. This analysis is based on 6,034 patients observed for at least 40 weeks after initiation of antiviral treatment. Results: Between 2/2014 and 5/2015, 1,074 patients with GT3 have been enrolled. Treatment has been initiated in 864 patients (70.3% male, median age 46.5 years, 34.7% treatment experienced, 33.2% with liver cirrhosis, 14.2% with platelets <90/nl, 11.6% with a HCV‐RNA >6 Mio IU/mL, 46.5% with a HCV‐RNA <0.8 Mio IU/mL). In 2/2016 a total of 591 patients reached the SVR12 follow‐up, but SVR12 data were missing from 31 patients and another 38 patients were not included in the per protocol analysis. Treatment regimens and SVR are shown in table 1. Conclusions: ITT‐SVR was <80% for SOF+RBV or SOF+LDV highlighting the need for better options in GT3 patients. PegIFN based therapy was still often used (>30%) and in combination with SOF+RBV associated with high SVR in compensated disease.However, side effects have to be considered. DCV+SOF±RBV have already been used in about 1/4 of patients with SVR around 90% even in difficult‐to‐treat patients.

Table 1. Overview of SVR in different treatment groups

Disclosures:

Markus Cornberg ‐ Advisory Committees or Review Panels: Merck (MSD Germamny), Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie

Joerg Petersen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead, Novartis, Merck, Bristol‐Myers Squibb, Gilead, Novartis, Merck; Grant/ Research Support: Roche, GlaxoSmithKline, Roche, Glaxo SmithKline; Speaking and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck

Klaus H. Boeker ‐ Consulting: Janssen; Speaking and Teaching: MSD, Roche, Gilead, BMS, Falk Foundation, Novartis, AbbVie

Stefan Christensen ‐ Advisory Committees or Review Panels: BMS, Abbvie, Janssen, ViiV, Gilead, MSD; Speaking and Teaching: Gilead, MSD, Abbvie, BMS, Janssen

Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Michael P. Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

Dietrich Hueppe ‐ Advisory Committees or Review Panels: Roche, MSD, Novatis, Gilead, BMS, Janssen, AbbVie

Thomas Berg ‐ Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis, Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Merck/MSD, Novartis, Merck, Bayer, Abbvie

Claus Niederau ‐ Advisory Committees or Review Panels: MSD, Abbvie, Jannsen, Gilead; Consulting: MSD; Grant/Research Support: MSD; Speaking and Teaching: MSD, Abbvie, BMS, Roche, Gilead

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie Deutschland GmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

The following people have nothing to disclose: Andreas Schober, Guenther Schmutz, Ralph Link, Karl‐Georg Buescher

¹Gastroenterology, Hepatology und Endocrinology, Hannover Medical School, Hannover, Germany; ²ifi‐institute for interdisciplinary medicine, Hamburg, Germany; ³University Hospital Würzburg, Würzburg, Germany; ⁴MVZDr.Eisenbach Dr.Simon Dr.Schwarz GbR, Leverkusen, Germany; ⁵Center of Hepatology, Hannover, Germany; ⁶Charité Campus Virchow‐Klinikum (CVK), Berlin, Germany; ⁷I. Dept. of Medicine, Johannes Gutenberg University Mainz, Mainz, Germany; ⁸Department of Internal Medicine I, UK S‐H, Campus Kiel, Kiel, Germany; ⁹e. factum GmbH, Butzbach, Germany; ¹⁰J. W. Goethe‐University Hospital, Frankfurt, Germany; ¹¹Center of Gastroenterology, Herne, Germany; ¹²Department of Hepatology, University Hospital Leipzig, Leipzig, Germany; ¹³Leberstiftungs‐GmbH Deutschland, Hannover, Germany

Introduction: Direct‐acting antiviral (DAA) regimens improved the efficacy of chronic HCV treatment. Phase 3 trials suggested lower response rates in patients with liver cirrhosis. However, there is limited information on the efficacy of DAA therapies in interferon‐ineligible patients with advanced cirrhosis. To what extent liver function improves in cirrhotic patients receiving interferon‐free therapies is unknown. Methods: The DHC‐R (Deutsches Hepatitis C‐Register, German Hepatitis C‐Registry) is a national multicenter real‐world cohort including approx. 9,300 patients. Patients are treated at the discretion of a physician Data are collected by a web‐based system Data quality is analyzed by plausibility checks and on site monitoring. This data analysis is based on 6,034 patients who were observed for at least 40 weeks after initiation of antiviral treatment Patients with advanced liver cirrhosis, defined by at least one of the following criteria: FibroScan >20kPa, thrombocytes <90,000/μl, albumin <35g/l or signs of liver decompensation, were analyzed. Results: 763 patients had advanced liver cirrhosis (median MELD‐Score 9; range 6‐32), 632 patients with FU week 12 were included. The majority of patients was infected with HCV‐genotype 1 (n=592); HCV‐gen‐ otypes 2, 3, 4 and 6 were present in 17, 124, 28 and 1 patient, respectively Patients received different treatment regimens. Overall, SVR was achieved in 88.0% of the patients (ITT). SVR rates according to the regimen ranged from 66 to 100%. DAA therapy lead to SVR rates (ITT) of 91.1%, 80.0%, 72.7% and 82.6% for HCV‐ genotype 1 (n =460), 2 (n =12), 3 (n=64) and 4 (n=19), respectively. Liver function parameters including albumin, bilirubin and prothrombin time improved in the majority of patients during antiviral therapy/follow‐up. The median platelet count, as a clinical marker of portal hypertension, increased from 88,000/^l at baseline to 111,000/ ^l during follow‐up (p<0.05). Creatinine levels were stable during antiviral treatment SAEs were reported in 8.1% and 6 patients died during the observation period. Conclusions: This real‐world cohort confirms that DAA treatment is feasible in patients with advanced liver cirrhosis leading to a restoration of liver function. A broad spectrum of individual treatment regimens was applied reflecting individualization of treatment in this difficult‐to‐treat cohort.

Disclosures:

Katja Deterding ‐ Speaking and Teaching: AbbVie, MSD/Merck, Gilead

Joerg Petersen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead, Novartis, Merck, Bristol‐Myers Squibb, Gilead, Novartis, Merck; Grant/ Research Support: Roche, GlaxoSmithKline, Roche, GlaxoSmithKline; Speaking and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck

Hartwig H. Klinker ‐ Advisory Committees or Review Panels: AbbVie, BMS, Gilead, Hexal, Janssen, MSD; Grant/Research Support: AbbVie, BMS, Gilead, Janssen, MSD, Arrowhead, Novartis; Speaking and Teaching: AbbVIe, BMS, Gilead, Janssen, MSD

Karl‐Georg Simon ‐ Advisory Committees or Review Panels: AbbVie, BMS, JANSSEN, MSD; Speaking and Teaching: AbbVie, BMS, FALK, GILEAD, JANSSEN, NORGINE, MERZ, MSD

Klaus H. Boeker ‐ Consulting: Janssen; Speaking and Teaching: MSD, Roche, Gilead, BMS, Falk Foundation, Novartis, AbbVie

Eckart Schott ‐ Advisory Committees or Review Panels: Gilead, Roche, Bayer, BMS, Abbvie, Janssen, MSD; Speaking and Teaching: Gilead, Novartis, Roche, MSD, Bayer, Falk, BMS, Janssen, Abbvie

Tim Zimmermann ‐ Advisory Committees or Review Panels: Abbvie; Speaking and Teaching: BMS

Markus Cornberg ‐ Advisory Committees or Review Panels: Merck (MSD Ger‐ mamny), Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie

Rainer Günther ‐ Speaking and Teaching: Roche Pharma AG, Gilead, AbbVie Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Christoph Sarrazin ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD; Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche, Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens, Falk, Abbvie, Bristol‐Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen

Michael P. Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest, AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

Dietrich Hueppe ‐ Advisory Committees or Review Panels: Roche, MSD, Novatis, Gilead, BMS, Janssen, AbbVie

Heiner Wedemeyer ‐ Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk, Abbvie, Novartis, GSK, Roche Diagnostics, Eiger; Consulting: MyrGmbH; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott, Roche Diagnostics; Speaking and Teaching: BMS, MSD, Novartis, ITF, Abbvie, Gilead

Thomas Berg ‐ Advisory Committees or Review Panels: Gilead, BMS, Roche, Tibotec, Vertex, Jannsen, Novartis, Abbott, Merck, Abbvie; Consulting: Gilead, BMS, Roche, Tibotec; Vertex, Janssen; Grant/Research Support: Gilead, BMS, Roche, Tibotec; Vertex, Jannssen, Merck/MSD, Boehringer Ingelheim, Novartis, Abbvie; Speaking and Teaching: Gilead, BMS, Roche, Tibotec; Vertex, Janssen, Merck/MSD, Novartis, Merck, Bayer, Abbvie

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie Deutschland GmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

¹Hop Cochin, Paris, France; ²Hop H Mondor, Creteil, France

Background Data on real‐life use of direct acting antivirals (DAAs) in the treatment of chronic hepatitis C are scarce. We report the real‐life results of the ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) ± dasabuvir (DSV) combination in HCV genotype‐1 or 4‐infected patients. Methods ANRS CO22 HEPATHER « Therapeutic options for hepatitis B and C: a French cohort » is a multicenter observational cohort which aims to include 15 000 HCV‐ and 10 000 HBV‐infected patients (http://ClinicalTrials.gov, NCT01953458). We selected all cohort participants (n=277) with a HCV genotype 1 (n=223/80.5%) or genotype 4 (n=54/19.5%) infection who initiated a combination of PTV/r 150/100 mg/d and OBV 25 mg/d with (GT1) or without (GT4) DSV 500 mg/d, with (n= 137) or without (n= 140) ribavirin (RBV) (1‐1.2 g/d) before October 1st, 2015. The mean age was 58 years, cirrhosis F4 and F3 fibrosis was present in 52/94 (18.8/33.9%) patients, respectively and the duration of therapy was mainly 12 weeks. The main endpoint criteria was sustained virological response (SVR12) defined by the undetectability of HCV RNA 12 weeks after the last treatment intake. Findings: Population characteristics and SVR4 and SVR12 are presented in the Table A SVR4 and a SVR12 was obtained in 96/101 (95 %) and 88/91 (96.7 %) of patients. Interpretation: In real life setting, the OBV/PTV/r+/‐DSV combination is associated with a high rate of SVR12, higher than 92 %, in patients infected by genotype 1 or 4 Results on all patients treated with OBV/PTV/r+/‐DSV and included in the cohort will be presented Failure associated factors will be analyzed.

Population description, SVR4, and SVR12

Disclosures:

Hélène Fontaine ‐ Board Membership: Abbvie, Gilead, BMS, Janssen; Independent Contractor: gilead, BMS, MSD, Roche, Janssen

Christophe Hezode ‐ Speaking and Teaching: Roche, BMS, MSD, Janssen, abbvie, Gilead

Françoise Roudot‐Thoraval ‐ Advisory Committees or Review Panels: Roche, gilead; Consulting: LFB biomedicaments; Speaking and Teaching: gilead, Janssen, BMS, Roche, Abbvie

Stanislas Pol ‐ Board Membership: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Glaxo Smith Kline, Roche, MSD, Novartis; Grant/ Research Support: Gilead, Roche, MSD; Speaking and Teaching: Bristol‐Myers‐Squibb, Boehringer Ingelheim, Tibotec Janssen Cilag, Gilead, Roche, MSD, Novartis

¹Intercentre Unit of Digestive Diseases, Virgen del Rocío ‐ Virgen Macarena University Hospitals, Sevilla, Spain; ²Ciberehd, Institute of Biomedicine of Sevilla, Sevilla, Spain; ³Valme University Hospital, Sevilla, Spain; ⁴Ciberehd, San Cecilio University Hospital, Granada, Spain; ⁵Ciberehd, Vall d'Hebron University Hospital, Barcelona, Spain; ⁶Agencia Sanitaria Costa del Sol Hospital, Marbella, Spain; ⁷Marqués de Valdecilla University Hospital, Santander, Spain; ⁸Reina Sofía University Hospital, Córdoba, Spain; ⁹Virgen de la Victoria University Hospital, Málaga, Spain; ¹⁰Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain; ¹¹IDIBAPS, Ciberehd, Clinic University Hospital, Barcelona, Spain; ¹²General University Hospital, Valencia, Spain

Background: The advent of new direct‐acting antivirals has dramatically increased the SVR rates in Hepatitis C (HCV), with fewer adverse effects. However, the eradication of the virus could not be associated with a better prognosis in all patients. Aim: To assess the impact of basal comorbidities on the overall benefit of HCV patients treated with IFN‐free therapies. Methods: Multicenter study including prospectively 1,038 HCV patients (cirrhosis 71%) treated with IFN‐free therapies. Basal comorbidities were evaluated by: a) Charlson Comorbidity Index (CCI) (Charlson, 1987); b) Modified Charlson Comorbidity Index (mCCI) (Berkman, l992); c) CirCom Index (Jepsen, 2014). Liver and non‐liver related life‐threatening and serious adverse events were collected within the first year of treatment. Results: Adverse events were found in 14.5% (150/1,038) of overall cohort, with 2% (21/1,038) of deaths, during 7.5±3.1 months of follow‐up. CCI (3.4±1.7 vs. 2.2±1.6; p=0.0001), mCCI (0.9±1 vs. 0.4±0.8; p=0.0001) and CirCom (0.7±0.9 vs. 0.3±0.6; p=0.0001) were higher in patients suffering from adverse events Age, platelet count, creatinine, albumin and total bilirubin, as well as the presence of cirrhosis were also related to adverse events. An algorithm to predict and identify low‐, moderate‐ and high‐risk groups was constructed using CRT growing method (Figure). These groups were subsequently introduced in Kaplan‐Meier curve for adverse events (logRank 135.318; p<0.0001) and mortality (logRank 72.134; p<0.0001). Conclusion: HCV patients showing higher basal comorbidities showed more risk of suffering poor prognosis. A rapid and objective algorithm, including Charlson Comorbidity Index, helps to identify patients with increased rates of mortality and adverse events within first months of antiviral therapy. Thus, we could determine the overall benefit of DAA therapy beyond of the eradication of the virus.

Disclosures:

Xavier Forns ‐ Consulting: Jansen, Abbvie; Grant/Research Support: Jansen, Abbvie

Jose L. Calleja ‐ Advisory Committees or Review Panels: Gilead, Abbvie ; Speaking and Teaching: Abbvie, Gilead, Janssen, BMS

Javier Crespo ‐ Advisory Committees or Review Panels: Abbvie, Janssen, BMS; Grant/Research Support: MSD, Gilead

Maria Buti ‐ Advisory Committees or Review Panels: Gilead, Janssen, MSD; Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead, Janssen, BMS

The following people have nothing to disclose: Javier Ampuero, Carlota Jimeno, Rosa Quiles, Nieves Palomo, Guillermo Ontanilla, Jose Miguel Rosales‐Zabal, Susana Llerena, Patricia Cordero, Francisco Javier Serrano, A. Ortega, Marta Hernandez, Martin S. Bonacci, Moises Diago, Blanca Figueruela, Raul J. Andrade, Manuel De la Mata, Isabel Carmona, J. M. Navarro, Juan Manuel Pascasio, Javier Salmeron, Manuel Romero‐Gomez

¹Department of Internal Medicine I, Bonn University, Bonn, Germany; ²Infektiologikum, Frankfurt, Germany; ³Center for HIV and Hepatogastroenterology, Duesseldorf, Germany; ⁴Practice for Infectiology, Berlin, Germany; ⁵PraxisCityOst, Berlin, Germany; ⁶Praxiszentrum Kaiserdamm, Berlin, Germany; ⁷e.factum GmbH, Butzbach, Germany; ⁸Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; ⁹Center for infectious diseases, Berlin, Germany; ¹⁰Leberstiftungs‐GmbH Deutschland, Hannover, Germany

Introduction: More recently, cohort analyses have claimed that HIV co‐infection independently impairs the response to direct‐acting antiviral (DAA)‐based therapy against chronic hepatitis C (HCV) in real life cohorts (1). The aim of this study was therefore to compare SVR12 rates between HIV/HCV co‐infected and HCV mono‐infected subjects from the National German HCV cohort. Methods: The DHC‐R (Deutsches Hepatitis C‐Register, German Hepatitis C‐Registry) is a national multicenter real‐world cohort including approx. 9,300 patients. Patients are treated at the discretion of the physician. Data are collected by a web‐based system. Data quality is analyzed by plausibility checks and on site monitoring. This data analysis is based on 6,034 patients who were observed for at least 40 weeks after initiation of antiviral HCV treatment. Results: Overall, 459 HIV/HCV co‐infected and 5,411 HCV mono‐infected subjects were included into this analysis. Baseline characteristics for both groups are shown in Table 1. Overall, SVR12 rates across all genotypes in the ITT analysis were comparable between HCV mono‐ and HIV/HCV co‐infected individuals with 90.9% and 91.9% (SVR12 92.3% vs 92.6% for GT1 and 83.7% vs 88.9% for GT3), respectively. Neither treatment duration nor ribavirin use were different between both groups Also no difference in HCV SVR12 rate was observed between cirrhotic patients with and without HIV co‐infection (89.7% vs 87.9%). Also in the subset of GT1 patients receiving 8 weeks of Ledipasvir/sofosbuvir no difference in SVR12 rates was noted between HIV‐ and HIV+ HCV patients (93,7% (n=478) vs. 95,8% (n=46)). Number of treatment discontinuations was low for both groups with 2.3 and 1.6%, accordingly. Conclusions: This analysis from a large national real‐life patient cohort finds no difference in HCV cure rates between HIV/HCV and HCV mono‐infected patients and therefore supports current HCV guidelines which no longer see a need to consider HIV co‐infected individuals as a special patient population. Neukam K et al., HIV coinfection impairs response to DAA‐based HCV therapy. EASL 2016; Abstract: LBP513

Disclosures:

Jürgen K. Rockstroh ‐ Advisory Committees or Review Panels: Abbvie, Cipla,BMS, Merck, Roche, Tibotec, Abbvie, Bionor, Tobira, ViiV, Abbott, Gilead, Janssen; Consulting: Novartis; Grant/Research Support: Gilead, Merck; Speaking and Teaching: BMS, Merck, Siemens, Tibotec, Gilead, Janssen, ViiV

Stefan Mauss ‐ Advisory Committees or Review Panels: BMS, AbbVie, ViiV, Gilead;Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD

Heike Pfeiffer‐Vornkahl ‐ Employment: efactum GmbH

Markus Cornberg ‐ Advisory Committees or Review Panels: Merck (MSD Germamny),Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie

Michael P. Manns ‐ Consulting: Roche, BMS, Gilead, Boehringer Ingelheim,Novartis, Enyo Pharma, Eiger, GSK, Merck/MSD, Janssen, Medgenics, Biotest,AbbVie; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS, AbbVie, Janssen; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis, AbbVie

German Hepatitis C‐Registry ‐ Grant/Research Support: AbbVie DeutschlandGmbH & Co. KG, Bristol‐Myers Squibb GmbH & Co. KGaA, Gilead Sciences GmbH, Janssen‐Cilag GmbH, MSD Sharp & Dohme GmbH, Roche Pharma AG

The following people have nothing to disclose: Thomas Lutz, Christiane Cordes,Heribert Hillenbrand, Arend Moll, Axel Baumgarten

¹King's College Hospital, London, UnitedKingdom; ²Dunedin Hospital, Dunedin, New Zealand; ³Monash Medical Centre, Melbourne, VIC, Australia; ⁴Gastreontorology Department, Binghmanton, NY; ⁵John Radcliffe Hospital, Radcliffe,United Kingdom; ⁶Storr Liver Centre, Westmead Millennium Institute for Medical Research, University of Sydney and Westmead Hospital, Sydney, NSW, Australia; ⁷Gartnavel General Hospital, Glasgow, United Kingdom; ⁸Nottingham University Hospitals NHS Trust and NIHR Biomedical Research Unit, Nottingham, United Kingdom; ⁹Virginia Mason Medical Center, Seattle, WA; ¹⁰Frimley Park Hospital, Frimley, United Kingdom; ¹¹South West Liver Unit, Derriford Hospital, Plymouth, United Kingdom; ¹²St George's Hospital University of London, London, United Kingdom; ¹³Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia; ¹⁴Sir Charles Gairdner Hospital, Nedlands, WA, Australia; ¹⁵Gastroenterology Research Institute, Vancouver, BC, Canada; ¹⁶Royal Liverpool Hospital, Liverpool, United Kingdom; ¹⁷Digestive and Liver Disease Center, Norfolk, VA; ¹⁸Wellington Hospital, Wellington, New Zealand; ¹⁹St George Hospital, Sydney, NSW, Australia; ²⁰Minnesota Gastroenterology, Saint Paul, MN; ²¹Nuffield Department of Medicine, Oxford NHIR BRC, Oxford, United Kingdom; ²²Gilead Sciences, Foster City, CA; ²³University of British Columbia, Division of Gastroenterology, Vancouver, BC, Canada; ²⁴Queen Mary University of London, Barts Health, London, United Kingdom

Background and Aims: Retreatment options for direct‐acting antiviral (DAA)‐experienced genotype 2 or 3 HCV‐infected patients are limited. Treatment‐experienced (TE) patients with genotype (GT) 2 HCV and cirrhosis, and treatment‐naïve (TN) and TE patientswith GT3 HCV with and without cirrhosis who relapsed following SOF+RBV treatment in the hase 3 Boson study were offered retreatment with SOF+PegIFN+RBV for 12 weeks. Methods: Thirty patients received open‐label SOF 400mg+PegIFN+RBV for 12 weeks. PegIFN was administered as 180 mg s.c weekly injection, and RBV was administered orally 1000‐1200 mg in a divided daily dose. The primaryendpoint was SVR12. Results: Of these 30 patients, 90% were male, all but one (97%) had GT3 HCV infection, 43% had cirrhosis. All patients completed the treatment period per protocol. Overall, SVR12 was achieved by 80% (24/30). Among patients with GT3 HCV infection, 83% (24/29) achieved SVR12, SVR12 rates were higher among those without cirrhosis (88%) than those with cirrhosis (75%), and among those previously treated for 24 weeks (100%) than 16 weeks (74%) (Table).The single GT2 patient relapsed at post‐treatment Week 4 visit. Prior to retreatment, 4 of the 30 patients had NS5B nucleoside inhibitor RASs (N142T n=1, L159F n=2, V321n=1) and all achieved SVR12 after retreatment.The most common adverse events were fatigue, headache, nausea, myalgia,pyrexia, influenza‐like illness, pruritus, and rash. No patient experienced an AE leading to study drug discontinuation. One patient experienced an SAE of shoulder pain one day after treatment completion that was assessed as not related to study drug by the investigator. Conclusions: SOF+PegIFN+RBV provided a high rate of SVR12 in non‐cirrhotic patients with GT3 HCV infection who relapsed following SOF+RBV therapy. However, PegIFN based regimens are not favored by patients and highly effective and well tolerated IFN free regimens for treatment of GT3 HCV are needed.

SVR12 rates in GT3 patients, by cirrhosis status and prior regimen

Kosh Agarwal ‐ Advisory Committees or Review Panels: Gilead, BMS, Novartis, Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead, BMS, GSK

Stephen Pianko ‐ Advisory Committees or Review Panels: Roche, Novartis, GILEAD, Roche, Novartis; Consulting: GILEAD; Speaking and Teaching: JANSSEN, BMS

Leslie Bank ‐ Grant/Research Support: AbbVie Virology, Gilead, Merck, BMS; Speaking and Teaching: AbbVie Immunology, Gilead, Merck, BMS

Jacob George ‐ Advisory Committees or Review Panels: Pharmaxis, BMS, MSD, Gilead, Janssen, Abbvie; Grant/Research Support: MSD

Stephen D. Ryder ‐ Advisory Committees or Review Panels: Abbvie, Gilead, MSD, MBS, Norgine

Matthew Cramp ‐ Advisory Committees or Review Panels: Gilead, AbbVie, BMS, Merck, Janssen; Grant/Research Support: Gilead, AbbVie, BMS, Merck, Janssen; Speaking and Teaching: Gilead, AbbVie, BMS, Merck, Janssen

Daniel M. Forton ‐ Advisory Committees or Review Panels: Gilead, Merck, Abbvie; Speaking and Teaching: Janssen, BMS

Barbara A. Leggett ‐ Advisory Committees or Review Panels: MSD, MSD, MSD, MSD, BMS, Abbvie; Speaking and Teaching: Roche, Roche, Roche, Roche, Gilead

Alnoor Ramji ‐ Advisory Committees or Review Panels: BMS, Merck, Gilead, Janssen, Lupin, Boehringer Ingelheim; Grant/Research Support: BMS, Abbvie, Merck, Gilead, Vertex, Novartis, Boehringer Ingelheim

Michael J. Ryan ‐ Advisory Committees or Review Panels: gilead; Speaking and Teaching: gilead

Amany Zekry ‐ Advisory Committees or Review Panels: GILEAD, BMS, MSD, Abbvie

Diana M. Brainard ‐ Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences

Benedetta Massetto ‐ Employment: Gilead Sciences, Inc. ; Stock Shareholder: Gilead Sciences, Inc

John G. McHutchison ‐ Employment: gilead; Stock Shareholder: gilead

Eric M. Yoshida ‐ Advisory Committees or Review Panels: Gilead Sciences Inc; Grant/Research Support: Abbvie, Merck Inc, Springbank, Jannsen Inc, Gilead Sciences Inc, Intercept; Speaking and Teaching: Gilead Sciences Inc, Merck Canada, Celgene Canada, Merck Inc

Graham R. Foster ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS, Alnylam; Board Membership: Boehringer Ingelheim; Grant/Research Support: Roche, Chughai, Springbank; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen

The following people have nothing to disclose: Michael Schultz, Jane Collier, Matthew Priest, Blaire E. Burman, Kuldeep Cheent, Gerry C. MacQuillan, Paul Richardson, Nigel Stace, Donald L. Zogg, Eleanor Barnes, Frances Chen, Mani Subramanian

¹Department of Medicine, Hofstra Northwell School of Medicine, Manhasset, NY; ²University Hospital of Nice, Digestive Centre, Nice, France; ³Division of Hepatology, School of Medicine, University of Miami, Miami, FL; ⁴Swedish Medical Centre, Seattle, WA; ⁵Hopital Saint Joseph, Marseilles, France; ⁶Viral Hepatitis Center, Johns Hopkins University, Baltimore, MD; ⁷Scripps Clinic and Scripps Translational Science Institute, La Jolla, CA; ⁸AbbVie Inc., North Chicago, IL; ⁹Mount Sinai Beth Israel, New York, NY

Introduction: HCV infection is associated with an increased risk of chronic kidney disease (CKD), and management of HCV in patients with advanced CKD remains a challenge. We previously reported that treatment of HCV GTl‐infected patients with ombitasvir, paritaprevir (identified by AbbVie and Enanta) with the pharmacokinetic enhancer ritonavir, and dasabuvir (OBV/PTV/r + DSV) ± RBV was not associated with overall changes in renal function However we observed a mean gain in eGFR following treatment in patients with baseline (BL) eGFR 60‐≤ 90 (+1.3 mL) or ≤ 60 mL/min/1.73 m² (+6.0 mL). This analysis investigated BL patient characteristics and laboratory predictors for eGFR improvement with OBV/PTV/r + DSV ± RBV. Methods: Renal function was categorized by eGFR using the MDRD equation and patients were grouped according to BL eGFR: > 90, 60‐90, or < 60 mL/min/1.73 m². Analysis included patients treated with OBV/PTV/r + DSV ± RBV in 9 trials: SAPPHIRE‐I/II; TURQUOISE‐II/III; TOPAZ‐II; PEARL‐II/III/ IV; and RUBY‐I (excluding patients on dialysis). BL factors associated with a ≥ 10 mL/min/1.73 m² increase in eGFR were examined by stepwise logistic regression The primary model excluded two studies (RUBY‐I and TURQUOISE‐III) that did not include BL urinalysis Additional models included these studies and explored other degrees of change in eGFR. Results: BL characteristics are shown in Table 1. In the primary model, a > 10 mL/min/1.73 m² increase in eGFR was associated with BL proteinuria (OR 1.647; 95% CI 1.320‐2.054; p<0.001), history of diabetes (OR 1.512; 95% CI 1.059‐2.161; p=0.023), BMI (OR 0.948; 95% CI 0.926‐0.971; p<0.001), and Black race (OR 0.596; 95% CI 0.384‐0.923; p=0.021). Conclusion: BL proteinuria, history of diabetes, lower BMI, and nonBlack race were identified as predictors of an eGFR increase of ≥10 mL/min/1.73 m² after OBV/PTV/r + DSV ± RBV treatment. Longer follow‐up is needed to confirm any beneficial effect on renal function or possible clinical outcomes associated with eradication of HCV with this treatment.

Baseline characteristics

* Excludes RUBY‐I and TURQUOISE‐III.

Disclosures:

David E. Bernstein ‐ Consulting: abbvie, Merck, Janssen; Grant/Research Support: GIlead, abbvie, BMS, Janssen; Speaking and Teaching: Gilead

Paul Martin ‐ Advisory Committees or Review Panels: BMS; Grant/Research Support: Merck, Gilead, Janssen, Abbvie

Kris V. Kowdley ‐ Advisory Committees or Review Panels: Abbvie, Enanta, Gilead, Intercept, Merck, Novartis, Trio Health, Verylx; Grant/Research Support: Abbvie, Evidera, Galectin, Gilead, Immuron, Intercept, Merck, NGM Biopharma, Novartis, Tobira, Trio Health; Speaking and Teaching: Gilead, Intercept

Marc Bourlière ‐ Advisory Committees or Review Panels: Schering‐Plough, Bohringer inghelmein, Schering‐Plough, Bohringer inghelmein, Transgene; Board Membership: Bristol‐Myers Squibb, Gilead, Idenix; Consulting: Roche, Novartis, Tibotec, Abott, glaxo smith kline, Merck, Bristol‐Myers Squibb, Novartis, Tibotec, Abott, glaxo smith kline; Speaking and Teaching: Gilead, Roche, Merck, Bristol‐Myers Squibb

Mark S. Sulkowski ‐ Advisory Committees or Review Panels: Merck, AbbVie, Janssen, Gilead, Trek, Cocrystal; Grant/Research Support: Merck, AbbVie, Janssen, Gilead

Paul J. Pockros ‐ Advisory Committees or Review Panels: Janssen, Merck, BMS, Gilead, AbbVie; Consulting: Lumena, Beckman Coulter; Grant/Research Support: Intercept, Janssen, BMS, Gilead, Lumena, Beckman Coulter, AbbVie, RMS, Merck; Speaking and Teaching: AbbVie, Janssen, Gilead

Lois M. Larsen ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Diana L. Shuster ‐ Employment: AbbVie

Daniel E. Cohen ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Boris Renjifo ‐ Employment: AbbVie; Stock Shareholder: AbbVie

Ira M. Jacobson ‐ Consulting: AbbVie, Achillion, Bristol Myers Squibb, Intercept, Gilead, Janssen, Merck, Trek; Grant/Research Support: AbbVie, Bristol Myers Squibb, Gilead, Janssen, Merck; Speaking and Teaching: AbbVie, Bristol Myers Squibb, Gilead, Janssen

The following people have nothing to disclose: Albert Tran

¹Faculty of Medicine and Life sciences, Hasselt University, Tongeren, Belgium; ²Department of Hepatology and Gastro‐Enterology, University Hospitals Gent, Gent, Belgium; ³Department of Gastro‐Enterology and Hepatology, ZNA Stuivenberg, Antwerp, Belgium; ⁴Department of Gastro‐Enterology and Hepatopancreatology, Erasme Hospital, Brussels, Belgium; ⁵Department of Gastro‐Enterology and Hepatology, University Hospitals UZAntwerpen, Antwerp, Belgium; ⁶Department of Gastro‐Enterology and Hepatology, Hôpital Saint‐Pierre, Brussels, Belgium; ⁷Department of Gastro‐Enterology and Hepatology, AZ Delta, Roeselare, Belgium; ⁸Department of Gastro‐Enterology and Hepatology, AZ Damiaan, Oostende, Belgium; ⁹Department of Gastro‐Enterology and Hepatology, University Hospitals KULeuven, Leuven, Belgium; ¹⁰Department of Gastro‐Enterology and Hepatology, Hôpital HIS Bracops, Brussels, Belgium; ¹¹Department of Gastro‐Enterology and Hepatology, AZ Sint Maarten, Mechelen, Belgium; ¹²Department of Gastro‐Enterology and Hepatology, Jessa Hospital, Hasselt, Belgium; ¹³Department of Gastro‐Enterology and Hepatology, AZ Maria Middelares, Gent, Belgium; ¹⁴Department of Gastro‐Enterology and Hepatology, AZ Groe‐ ninge, Kortrijk, Belgium; ¹⁵Faculty of Sciences, Mathematics and Statistics, Centre for Statistics, Hasselt Universlty, Hasselt, Belgium; ¹⁶Department of Gastro‐Enterology and Hepatology, Ziekenhuis Oost‐Limburg, Genk, Belgium

Introduction Hepatitis C viral infection (HCV) remains one of the main causes of chronic liver disease worldwide. It has now become a curable disease due to the development of direct acting antivirals (DAA). Therefore, the WHO has set a target to eliminate HCV completely. To reach this target, people who inject drugs (PWID) need to be treated as they are the largest risk group for HCV in the Western world. Furthermore, treatment of HCV in PWID is recommended by the treatment guidelines. The aim was to study the uptake and outcome of treatment for HCV in PWID and the general population. Method We performed a Belgian, nation‐wide, retrospective cohort study in 12 hospitals. All patients who were treated in these hospitals with simeprevir‐sofosbuvir, daclatasvir‐sofosbuvir, or ombitasvir/paritaprevir ritonavir ‐ dasabuvir between December 2013 and November 2015 were included. These regimens were chosen based on the Belgian reimbursement criteria All centers were experienced in treating HCV infected PWID. In case antiviral treatment was started, data were collected in a central database. PWID were subdivided in active users, defined by drug use during therapy with DAA, and former PWID. A PWID was defined by someone who used intravenous drugs at least once. Results The study population consisted of 419 patients: 111 PWID, subdivided in 23 active users and 88 former PWID, and 308 non‐PWID treated with one of the above DAA regimens ± ribavirin. PWID (active and former) were younger (p=0.001), predominantly male (p=0.001), had a lower BMI (p=0.006), abused more alcohol (p=0.001), used more benzodiazepines (p=0.001) and were more infected with genotype 1a, 3 and 4 (p=0.001). Active PWID were less treatment experienced (p=0.05) and used less comedications (p=0.043) There were no differences in fibrosis score (F3, F4) (p=0.454) between all groups. PWID had a similar rate of side‐effects (p=0.961). There was a trend towards more psychological complaints in PWID (p=0.051). Similar rates of treatment completion (p=0.095) and SVR (p=0.372) were achieved irrespective of active substance abuse. Conclusion Although DAA are safe and effective also in (active) drug users, PWID are still highly underrepresented in a Belgian treatment cohort, even the era of new DAA therapy. As this risk‐group is at the heart of the HCV epidemic, more efforts are necessary to reach this group

Disclosures:

Christophe Moreno ‐ Consulting: Abbvie, Janssen, Gilead, BMS, MSD; Grant/ Research Support: Janssen, Gilead, Roche, Astellas, Abbvie

Thomas Vanwollegem ‐ Advisory Committees or Review Panels: Gilead, Abbvie, BMS; Grant/Research Support: BMS, Gilead, Roche

Wim Verlinden ‐ Grant/Research Support: Gilead, Bristol‐Myers Squibb

Jean‐Pierre Mulkay ‐ Grant/Research Support: GILEAD, BMS

Frederik Nevens ‐ Consulting: MSD, CAF, Intercept, Gore, BMS, Abbvie, Novartis, Durect, Janssens‐Cilag, Ono Pharma, Promethera Biosciences; Grant/ Research Support: Ferring, Roche, Astellas, Novartis, Janssen‐Cilag, Abbvie

Geert Robaeys ‐ Advisory Committees or Review Panels: MSD, Janssens, Gilead, Abbvie, BMS

The following people have nothing to disclose: Rob Bielen, Hans Van Vlierberghe, Stefan Bourgeois, Jochen Decaestecker, Mike Cool, Chantal de Galocsy, Lode Van Overbeke, Filip Janssens, Christophe Van Steenkiste, Francois D'heygere, Wilfried Cools

¹University of Washington, Seattle, WA; ²Veterans Affairs Puget Sound Healthcare System, Seattle, WA

Background: Whether alcohol use negatively impacts hepatitis C virus (HCV) treatment outcomes in the era of direct antiviral agents (DAAs) is unknown. Alcohol Use Disorders Identification Test Consumption (AUDIT‐C) questionnaires have been recommended to be administered annually in the VA since 2008 to screen for unhealthy alcohol use. This study examined associations between levels of drinking ascertained by screening AUDIT‐C questionnaires administered within one year prior to DAAs and response to DAAs in the national Veterans Affairs (VA) healthcare system. Methods: Out of 17,487 patients who initiated HCV DAAs during the 18‐month period from January 1, 2014 to June 30, 2015, 15,151 (87%) had completed an AUDIT‐C questionnaire within one year prior to initiating therapy and comprised the final study sample DAAs included: sofosbuvir (SOF), ledipasvir/sofosbuvir (LDV/SOF) or ombit‐ asvir‐paritaprevir‐ritonavir, and dasabuvir (PrOD) Sustained virologic response (SVR) was defined as a viral load below the limit of quantification performed ≥12 weeks after the end of treatment. AUDIT‐C scores were categorized as 0 (abstinence), 1‐3 (low‐level drinking) and 4‐12 (unhealthy drinking) in men or 0, 1‐2 and 3‐12 in women. Rates of SVR and 95% confidence intervals were calculated and we performed multiple logistic regression models, with and without imputing missing SVR data. Results: The sample was mostly male (96.7%), 28.9% were black, 30% had cirrhosis, mean age was 61 ±7 years and the distribution of HCV genotypes was 1 (79.8%), 2 (12.5%), 3 (7.0%) and 4 (0.8%). Alcohol abstinence was reported in 10,387 (68.5%), low‐level drinking in 3422 (22.6%) and unhealthy drinking in 1342 (8.9%). There were no significant differences in SVR rates between abstinent (SVR 91%, 95% CI 91‐92%), low‐level drinking (SVR 93%, 95% CI 92‐94%) or unhealthy drinking (SVR 91%, 95% 89‐92) categories in the entire sample, or among subgroups defined by HCV genotype, cirrhosis, or HIV status AUDIT‐C categories were not significantly associated with SVR after adjustment for most important predictors of SVR in multivariable logistic regres‐sion models. Conclusions: A substantial proportion (31.5%) of HCV‐infected patients treated with DAAs in 2014‐15 reported not being abstinent from alcohol based on a screening AUDIT‐C questionnaire performed within a year prior to initiating DAAs. However, rates of SVR were high, even among persons with low‐level and unhealthy alcohol use and AUDIT‐C score was not associated with SVR.

Disclosures:

The following people have nothing to disclose: Judith Tsui, Emily Williams, Pamela Green, Kristin Berry, Feng Su, George N. loannou

Hepatology, National Liver Institute, Menoufiya, Egypt

Introduction: Insulin resistance (IR) is a common complication in patients with chronic HCV. The change in IR after treatment with direct acting antivirals (DAAs) is not known. Aim: To assess the impact of response to DAAs on the IR status in patients with chronic HCV. Methods: Five hundred and eighteen patients (366 treatment‐naïve and 152 pegylated interferon (PEG) and ribavirin (RBV) experienced) with positive HCV RNA for more than 6 months were enrolled. Patients with uncontrolled diabetes or other comorbidities, hepatic or extrahepatic malignancy, decompensated liver disease, or prior non‐response to DAAs were excluded. The Homeostatic Model Assessment (HOMA) was calculated before and 12 weeks after treatment and IR was defined as HOMA>1.9. Patients were treated according the treating physician's choice, and received one of the following DAAs protocols; 12 weeks of ombitasvir/ritonavir/ paritaprevir/RBV (n=28), sofosbuvir (SOF)/simeprevir (n=37), SOF/ravidasvir (n=101), SOF/PEG/RBV (n=195) or 24 weeks of SOF/RBV (n=157). Results: Patients' age was 50.7±10.4 years. They were mostly males (n=395, 76.3%), non‐diabetics (n=390, 75.3%), non‐F4 fibrosis (n=274, 52.9%) and most with pre‐treatment IR (n=415, 80.4%). Sustained virological response at 12 weeks post‐treatment (SVR12) was achieved in 471 patients (90.9%). There was no significant difference in pre‐treatment HOMA between responders and non‐responders (3.8±2.6 vs.4.5±3.3 respectively, p=0.122). HOMA improved significantly more in patients with SVR than in non‐responders (median decrease (IQR) = ‐1.09 (1.8) vs. ‐0.08 (2.26), p=0.002). The number of patients with IR decreased significantly in patients who achieved SVR (table) much more than in non‐responders (p<0.0001). All treatment protocols were associated with comparable HOMA improvement (p=0.222). Significant predictors of SVR12 included age <50 years (p=0.038; OR: 2.1, 95% CI: 1.042‐4.226), serum albumin ≥3.5 g/dL (p=0.035; OR: 2.14, 95% CI: 1.057‐4.338) and liver stiffness <10 kPa (p=0.017; OR: 2.59, 95% CI: 1.1835.682) but not pre‐treatment IR (p=0.075; 95% CI: 0.838‐1.009) Conclusion: Insulin resistance improves significantly in patients who achieve an SVR with different DAA regimens.

Number of Patients with IR Before and After Therapy

IR, insulin resistance; SVR, sustained virological response.

Patients with IR in responders vs. non‐responders: pre treatment: p=0.562, post treatment: p<0.0001

Disclosures:

Wael Abdel‐Razek ‐ Grant/Research Support: Gilead Sciences, Inc.

Imam Waked ‐ Advisory Committees or Review Panels: Janssen; Speaking and Teaching: Hoffman L Roche, BMS, Gilead, AbbVie

The following people have nothing to disclose: Mostafa G. Elhelbawy, Ayman Alsebaey, Mohammed Saad Hashem, Hassan A. El Shennawy

¹Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria; ²Ambulatorium Suchthilfe Wien, Suchthilfe Wien gGmbH, Vienna, Austria; ³Verein Dialog Wien, Vienna, Austria

Background: An important subgroup of people who inject drugs (PWID) receives opioid substitution therapy (OST) under direct observation of a physician or nurse at a low‐threshold drug treatment facility or pharmacy on a daily basis. Most of these patients suffer from psychiatric comorbidities and are reluctant or unable to go to specialized hepatitis centers. Our hypothesis was that chronic hepatitis C in these difficult‐to‐treat patients could be optimally managed if modern, interferon‐free regimens were applied together with OST under direct observation of a physician or nurse at a low‐threshold drug treatment facility. Methods: Fifty‐nine PWID with chronic hepatitis C and borderline compliance (male/female: 47/12; mean age: 39.1 ± 9.8 years; genotype (GT) 1/3/4: 46/12/1) started interferon‐free treatment of chronic hepatitis C at the “Ambulatorium Suchthilfe Wien” ‐ a low‐threshold drug treatment facility in Vienna, Austria Four patients were coinfected with HIV and 15 had liver cirrhosis. Patients received antiviral treatment together with OST under direct observation of a physician or nurse. Treatment‐naïve GT1‐patients without cirrhosis were treated with sofosbuvir/ledipasvir for eight weeks. For the other patients, the individual treatment regimen was selected according to GT, fibrosis stage, pretreatment, HIV‐status and current reimbursement policy of insurances. Results: Following this concept of directly observed therapy, adherence to antiviral therapy was excellent: Only two scheduled dates, out of 3.662 dates (0.06%), for ingestion of the antiviral therapy in combination with OST were missed by the 59 patients Till now, 29 patients (male/female: 24/5; mean age: 39.1 ± 7.0 years; GT1/3/4: 23/5/1; liver cirrhosis present in 8 patients) have completed treatment and a 12‐week follow‐up period Virologic healing of hepatitis C infection (sustained virologic response, SVR12) could be confirmed in all 29 patients (SVR12 rate: 100%). Conclusion: Directly observed therapy of chronic hepatitis C with interferon‐free all‐oral regimens at a low‐threshold drug treatment facility represents a promising new concept for treatment of patients with borderline compliance receiving OST By this concept chronic hepatitis C can be cured in a group of difficult‐to‐treat patients, who are unable to be treated at hepatologic centers. It should be stressed that successful treatment of these patients is not only beneficial for themselves but also for the general population because further transmission of the virus may be prevented.

Disclosures:

Michael Gschwantler ‐ Advisory Committees or Review Panels: Janssen, BMS, Gilead, AbbVie; Grant/Research Support: AbbVie, Gilead; Speaking and Teaching: Janssen, BMS, Gilead, AbbVie

The following people have nothing to disclose: Stephan Moser, Angelika Schütz, Katharina Marchart, Gerhard Rechberger, Doris Kalchbrenner, Sabrina Ambrosch, Julian Luhn, Enisa Gutic, Hans Haltmayer

¹Division of Gastroenterology,, Kurume University School of Medicine, Kurume, Japan; ²The Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyusyu, Japan; ³Hepatology, Saga Medical School, Saga, Japan

Purpose: In clinical trials, direct‐acting antivirals (DAA) display efficacy rates of 90‐99% against chronic hepatitis C (CHC), but it is unclear whether similar results are seen in routine practice. Our goal is to verify the efficacy and safety of DAAs treatment for CHC in a multicenter real‐world patients cohort from Japan. Methods: We prospectively enrolled 2,192 consecutive CHC patients in whom 24 weeks' daclatasvir and asunaprevir (DCV/ASV) (n=1,057), 12 weeks' sofosbuvir and ledipasvir (SOF/LDV) (n=701) for genotype 1 disease, or 12 weeks' sofosbuvir and ribavirin (SOF/RBV) (n=434) for genotype 2 disease was initiated during the period from September 2014 to April 2016. Results: 960 patients (43.8%) were male, and the patients' mean age was 66.8 (range: 19‐89) years. In addition, 766 patients (34.9%) had been pretreated with interferon‐based regimens. Liver cirrhosis was observed in 478 patients (21.8%), and 275 patients (12.5%) had a history of hepatocellular carcinoma Among the patients treated with DCV/ASV, the treatment discontinuation rate due to adverse events was 4.8% (40/834). The most common reason for discontinuation was increased alanine transaminase levels The 12‐week sustained viral response (SVR12) rate was 89.0% (738/872) The SVR rates of the patients with and without cirrhosis were 89.0% (235/264) and 90.1% (548/608) (p=0.6), respectively. The absence of NS5A‐Y93 variants and not having been treated with simeprevir were found to be significantly associated with a SVR (p<0.001). Among the patients treated with SOF/LDV, treatment discontinuation was only necessary in two patients (due to esophagitis and pneumonia, respectively), and the SVR4 or 12 rate was 99.1% (318/321). One patient with cirrhosis and NS5A‐L31 and Y93 variants relapsed after the therapy Among the patients treated with SOF/RBV, the treatment discontinuation rate was 1.7% (5/291), and the SVR4 or 12 rate was 96.2% (280/291). Of the 11 patients who did not achieve a SVR, 8 completed the treatment Of these 8 patients, 4 were cirrhotic, and the RBV dose was reduced in 3 patients Cirrhosis was found to be significantly associated with a non‐SVR (p=0.03). Conclusion: This cohort, which included a substantial proportion of cirrhotic patients, generally exhibited high response rates. HCV variants were associated with a non‐SVR among patients that were treated with DCV/ASV, and cirrhosis was associated with a reduction in the SVR rate among patients that were treated with SOF‐based regimens.

Disclosures:

The following people have nothing to disclose: Tatsuya Ide, Yuichiro Eguchi, Masaru Harada, Yuichi Honma, Shinji Iwane, Michiaki Okada, Teruko Arinaga‐Hino, Miyajima Ichiro, Ogata Kei, Reiichiro Kuwahara, Keisuke Amano, Takuji Torimura

¹Institute of Liver Studies, King's College Hospital, London, United Kingdom; ²The Blizard Institute, Queen Mary University of London, London, United Kingdom; ³NIHR Nottingham Digestive Diseases Biomedical Research Unit, University Hospital Nottingham, Nottingham, United Kingdom

Introduction DAA therapies in patients with advanced liver disease are effective and safe. However, impact on natural history and health economic benefits of treating this advanced, PT population remain unclear. This study assessed healthcare resource utilization from a clinical and cost perspective during, and 6 months (mths) post, DAA therapy compared to untreated HCV patients accepted onto the UK transplant waiting list. Methods The NHS England Expanded Access Program (EAP) enabled provision of 12 weeks therapy with Sofosbuvir (SOF) and an NS5A inhibitor, (Ledipasvir or Daclatasvir at clinicians discretion),+/‐ ribavirin (RBV) to a cohort of HCV positive patients with advanced, decompensated liver disease (Childs Pugh (CP) B7 and above). Of these, 178 patients fulfilled the NHSBT criteria for liver transplantation (LT), with 78 treated atKing's College Hospital (KCH) (median CP B7, range B7‐C13). Data collection on clinical interventions, support and ancillary therapies was prospective for the duration of therapy and 6 mths post Additionally, similar data were collected from a comparable retrospective ‘control’ cohort of 40 untreated HCV KCH patients meeting the NHSBT criteria with CP≥B7 (median B7, range B7‐C10) from inclusion onto the LT waiting list, until LT or death (majority within 9 mths) Results During DAA therapy minimal blood product and phone call support were needed (24 phone calls to nurse specialists and 44 to consultants, mean 11.5 and 11.6 mins respectively). Of the KCH EAP patients, 85% achieved SVR, with 27 patients at 6 mths follow‐up having complete resolution of the decompensation present at treatment initiation (ascites and encephalopathy) 13.6% with SVR were transplanted, 2.9% delisted and 3% died (due to overdose or progression) compared to 56% transplanted, 11% delisted and 33% deaths in the control cohort Clinical deterioration and worsening MELD necessitated more control cohort patients to be prioritized whilst on the waiting list This was reflected in the duration of emergency admissions (encephalopathy; sepsis/SBP and variceal bleed) to ITU (mean 0.45 days for patients with SVR vs 2.05 for control cohort) and to wards (mean 1.66 vs 19.82 days respectively). Overall a mean cost savingof £8473 per successfully treated patient was identified. Discussion This early analysis of health resource usage by PT patients treated with SOF and NS5A inhibitor +/‐ RBV demonstrates benefits in survival, quality of life and health resource utilization in this challenging cohort Full health resource usage data from 178 PT EAP patients will be presented The longer term impact of successful DAA therapy on natural history is still unclear.

Disclosures:

Graham R. Foster ‐ Advisory Committees or Review Panels: GlaxoSmithKline, Novartis, Boehringer Ingelheim, Tibotec, Gilead, Janssen, Idenix, GlaxoSmithKline, Novartis, Roche, Tibotec, Chughai, Gilead, Merck, Janssen, Idenix, BMS, Alnylam; Board Membership: Boehringer Ingelheim; Grant/Research Support: Roche, Chughai, Springbank; Speaking and Teaching: Roche, Gilead, Tibotec, Merck, BMS, Boehringer Ingelheim, Gilead, Janssen

Michael A. Heneghan ‐ Consulting: Novartis; Speaking and Teaching: Falk Pharma

William Irving ‐ Advisory Committees or Review Panels: Novartis, MSD, Janssen Cilag, Bristol Myers Squibb; Grant/Research Support: GSK, Pfizer, Janssen Cilag, Gilead Sciences, Abbvie; Speaking and Teaching: Janssen Cilag, Roche

Ivana Carey ‐ Grant/Research Support: Gilead, Roche; Speaking and Teaching: BMS

Kosh Agarwal ‐ Advisory Committees or Review Panels: Gilead, BMS, Novartis, Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead, BMS, GSK

The following people have nothing to disclose: Suman Verma, Matthew D. Sadler, Aisling B Considine, Kate Childs, Abid Suddle

¹Gastroenterology and Hepatology Unit., University Hospital Marqués de Valdecilla/Instituto de investigación Marqués de Valdecilla (IDIVAL), Santander, Spain; ²Department of Molecular Biology, Radiology and Medicine, University of Cantabria, Santander, Spain; ³Medical Service, El Dueso Penitentiary Centre, Santoña, Spain; ⁴Microbiology Unit, Complejo Hospitalario Universitario Granada‐Hospital San Cecilio, Instituto de Investigaciôn Biosanitaria IBS, Granada, Spain

Thanks to the National Strategy Plan for tackle Hepatitis C in Spain (2015/16), around 50,000 infected patients are to be cured, mainly F3‐F4 and as general population. However, that Plan also considers as a priority the infected patients in prisons. Accordingly we planned a project in a Northern region of Spain (Cantabria) with 600k inhabitants and focused to the regional long‐stay prison of El Dueso. Our objectives were to: 1) Perform a systematic screening and evaluation of infections related to blood‐borne viruses, 2) Evaluate the efficacy and safety of an IFN‐free antiviral regimen, including the impact on the rates of reinfections at short/long term. Methods: The project was planned to start in 1Q 2016 following 3 consecutive phases: 1) viral testing and characterization, 2) treatment of HCV infected inmates, 3) follow‐up of patients for 30 months. All new entries in the prison are to be tested immediately and treatment initiated in the first week if HCV‐positive The list of variables to be analyzed include: 1) Demographics, clinical, and virological variables, including NS5a baseline resistance and deep analysis of nucleotide sequence quasispecies complexity of HVR1 region, 2) Endothelial dysfunction and neurocognitive function tests before treatment and 6 months after, 3) Efficacy, safety and QoL throughout the study, and 4) Rates of persistent HCV infection, reinfection and super‐infection. Results: Up to now 436 inmates have been included being full tested for blood‐borne viruses The majority of inmates were male (98%) with a median age of 59 yrs. Seventy patients were anti‐HCV positive (16%), of these 52 (74%) were HCV RNA positive. HCV genotypes were GT3 (56%), GT1 (36%), and GT4 (8%). Seven patients were HIV‐coinfected (13%), and none HBV‐coinfected Fibrosis distribution was: F0‐1 51.9%; F2 11.5%; F3 13.4% and F4 23%. The mean MELD score was 8. All viremic patients have been treated with LDV/SOF+/‐ RBV 12 wks (49 patients) or 8 wks (3 patients). All patients achieved EOT response No serious AEs were reported and no patients discontinued due to AEs Baseline NS5A RAS were found in 19% of the patients and were more frequent in HCV GT3 (36%). Viral diversity of the HVR1 region was high, irrespective of the HCV genotype. In 4Q 2016 SVR12 will be available for all treated inmates, including the remaining variables of this long‐term study. Conclusions: In this Spanish prison the HCV prevalence is x15 times the described in the general population, showing a different profile of HCV genotypes and a high viral diversity in HVR1. An elimination program of this nature is intended as a pilot experience that could be extended to other prisons.

Disclosures:

Javier Crespo ‐ Advisory Committees or Review Panels: Abbvie, Janssen, BMS; Grant/Research Support: MSD, Gilead

The following people have nothing to disclose: Susana LLerena, Carmen Cobo, Silvia Alvarez, Angel Estebanez‐Gallo, Miguel M. Soler, Jose Ramon Pallas, Santiago Echevarria, Ana Saez, Jesus Aguero, Natalia Chueca, Raul Pellon, Juan Crespo, Antonio Cuadrado, Federico Garcia

¹Second University of Naples, Naples, Italy; ²Infectious Diseases, AO CAserta, Caserta, Italy; ³AO dei Colli, Naples, Italy; ⁴Internal Medicine, University of Salerno, Salerno, Italy; ⁵University Federico II of Naples, Naples, Italy

BACKGROUND: The aim of the present study was to investigate the association between theinosinetriphosphatase (ITPA) activity and the degree of anemia occurring during DAA/ RBV‐based therapy in patients with cirrhosis. METHODS:In a multicentric, prospective study we enrolled 227 patients with HCV‐related cirrhosis treated with DAA and RBV [median age 66 years (IQR 57‐71), 52.9% male, median BMl 26.4 (IQR 23.9‐28.4), 4.5% withChild B cirrhosis, 6.6% post‐liver transplants, 2.7% HIV]. HCV genotype 1a was identified in 10.2%,1bin 58.2%, 2 in 23.6%, 3 in 7.1% and 4 in 0.9%. The median of baseline hemoglobin levels were 14.1 g/dl (IQR 12.9‐15.0). Seventy‐two (32%) patients were treated with Sofosbuvir(SOF) plus RBV, 25.4% withOmbitasvir, Paritaprevir, Ritonavirand Dasabuvirplus RBV, 22.2% withSOF+Simepre‐ virplus RBV, 10.2% with SOF+Ledipasvir plus RBV, 8% with SOF+Daclatasvir plus RBV and 2.2% whit Ombitasvir, Paritaprevir, Ritonavir plus RBV. The median dose of RBV/mg/ kg was 12.9 (IQR 11.6‐14.6).All patients were screened for both the rs1127354 and rs7270101 ITPA single nucleotide polymorphisms using a direct sequencing. The predicted ITPA activity was based in according to previous study (Thompson 2010). RESULT. One‐hundred fifty (66.1%) patients (Group 1) had a normal (100%)ITPase activity, 48 (21.1%; Group 2) had moderate (60%)activityand 29 (12.8%; Group 3) minimal (≤30%)activity. In the three groups the decline of hemoglobin was evaluated from baseline to day 15 (delta 15) and to day 30 (delta 30) of treatment. In Group 1 the delta 15 and 30 were respectively ‐1.26 (SD ±0.97) and ‐1.9 (±1.2), decays more severe than those observed in group 2(‐0,7±0.99; p=0.006 and ‐1.5±1.4; p=0.10, respectively) and in group3(‐ 0.36±0.53;p=0.000; and ‐0.6±0.74;p=0.000). Also the prevalence ofanemia‐related events (reduction of RBV dose and/ oruse of erythropoietin and/or of blood transfusions)was more frequently observed in group 1 (12.7% at day 15 and 28.7% at day 30) than in group 2 (6.3% and 25%, respectively) and group 3(3.4% and 6.9%,p=0.047).A logistic regression analysis including the ITPA activity, age, sex, dose of Ribavirin andeGFRidentified the the ITPA activity and the dose of ribavirinas the only independent predictors of anemia‐related events (OR:4.66, IC 95%: 1.12‐19.31,p=0.03; OR:1.25, IC 95%: 1.11‐1.89,p<0.001; respectively) CONCLUSION. This study suggests that the polymorphisms in the ITPA gene influences the severity of anemia during the first month of a DAA‐based treatment in HCV‐related cirrhosis. Thus, ITPA polymorphism may drive the use of RBV in difficult‐to‐treat patients, such as cirrhotic and/or non responder patients

Disclosures:

Vincenzo Messina ‐ Advisory Committees or Review Panels: ABBVIE; Grant/ Research Support: JANSSEN, ROCHE

Marcello Persico ‐ Advisory Committees or Review Panels: abbvie; Grant/ Research Support: gilead

Giovanni B. Gaeta ‐ Advisory Committees or Review Panels: Janssen, Merck,

Abbvie, Roche; Speaking and Teaching: BMS, Gilead, merck

Ivan Gentile ‐ Consulting: Abbvie; Grant/Research Support: Gilead Sciences

The following people have nothing to disclose: Nicola Coppola, Stefania De Pascalis, Giovanni Di Caprio, Salvatore Martini, Giorgio de Stefano, Mario Starace, Gianfranca Stornaiuolo, Vincenzo Sangiovanni, Maria Stanzione, Rosa Zampino, Federica Calo, Luca Rinaldi, Alessandro Federico, Antonio Riccardo Buonomo, Guglielmo Borgia, Pietro Filippini

¹Division of Gastroenterology & Hepatology, Humanity & Health Medical Centre, Hong Kong, Hong Kong; ²State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; ³Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Hospital, Beijing, China; ⁴Department of Medicine, Xixi Hosipital, Hangzhou, China; ⁵Liver failure treatment and research centre, 302 Hospital, Beijing, China

Background and Aims: Hepatitis due to hepatitis B virus (HBV) reactivation has been reported in chronic hepatitis C (CHC) patients coinfected HBV, treated with either interferon‐based therapy or pan‐oral direct acting antivirals (DAAs). We compare the rate of hepatitis due to HBV reactivation and HCV sustained virologic response (SVR) in CHC patients co‐infected with HBV, treated with interferon‐based therapy versus DAAs. Methods: A systematic search of English literature from Jan 1^st 1990 to Dec 31^st 2015 in Pubmed, Embase, Ovid, and Cochrane databases was conducted in March 2016. Two independent reviewers systematically identified studies that examined the efficacy and safety of HCV antiviral therapies in HBV/HCV co‐infected patients A meta‐analysis was conducted using a random effects model to assess the primary outcome (HBV reactivation rate and incidence of hepatitis due to HBV reactivation) and secondary outcomes (HCV SVR rate for 24 weeks in patients treated with interferon and for 12 weeks in patients treated with DAAs) Case reports were included in the systematic review but excluded in the meta‐analysis. Meta‐analysis was done by Stata 13. Results: The search yielded 35 studies involving 1121 CHC patients. Majority of the studies (n=30) were using interferon. All studies reported SVR rates, 26 studies reported HBV reactivation, and 22 studies reported occurrence of hepatitis due to HBV reactivation. Excluding results from case reports, the overall SVR rate was 47% in HBV/HCV co‐infected patients, and the SVR rate was lower in patients treated with interferon (43%) than those treated with DAAs (100%, p<0.001). The overall HBV reactivation rate was 12.3% and no difference in HBV reactivation was observed in patients treated with interferon (12.4%) and those treated with DAAs (12.2%, p=0.90). Overall incidence of hepatitis due to HBV reactivation was 0.3% (0‐1.1% in patients treated with interferon vs. 0.2‐33.2% in those treated with DAAs, p=0.02). Most cases of HBV reactivation occurred during the follow‐up of interferon treatment (3 weeks to 72 months post‐treatment) while all cases were observed during DAAs treatment (4 to 11 weeks during treatment). Conclusions: In CHC patients co‐infected with HBV, HCV SVR rate was higher in those treated with DAAs than those treated with interferon Though there was no difference in HBV reactivation rates between DAAs and interferon based therapies, incidence of hepatitis due to HBV reactivation was higher in DAA treatment and HBV reactivation occurred much earlier in patients treated with DAAs than those treated with interferon.

Disclosures:

Jinlin Hou ‐ Consulting: Roche, Novartis, GSK, BMS, Abbovir; Grant/Research Support: Roche, Novartis, GSK

The following people have nothing to disclose: Cheng Wang, Bing Li, Jing Chen, Huiming Liu, Dong Ji, Qing Shao, Xiaoyong Zhang, Vanessa Wu, Yudong Wang, Lei Lu, Jian Sun, Guofeng Chen, George Lau

¹Translational research in liver and digestive diseases, Institute of Biomedicine of Seville‐ University Hospital Virgen del Rocio., Seville, Spain; ²Digestive disease, University Hospital Virgen del Valme, Seville, Spain; ³Neurology, University Hospital Virgen del Valme, Seville, Spain

Background: Associations have been found between HCV infection and systemic atherosclerosis, endothelial dysfunction and hypertension The carotid intima‐media thickness (CIMT) is currently one of the most widely used noninvasive measures of atherosclerosis. The ankle brachial index (ABI) is a sensitive tool for peripheral artery disease and can also be used to assess systemic atherosclerosis. Aim: To analyze the impact of IFN‐ free treatment on the cardiovascular risk in HCV mono‐infected patients. Methods: We recruited prospectively 82 consecutive patients eligible for direct‐acting antivirals. We measured the cardiovascular risk according to: a) carotid intima‐media thickness (CIMT), >0.9mm was considered pathological; b) ankle‐brachial index (ABI), <0.9 was considered pathological We classified patients in two groups accordingly: a) non‐ improvement/worsening CV risk group, showing pathological CIMT or ABI after the treatment; b) improvement/non‐worsening CV risk group, showing normal CIMT or ABI after the treatment. In addition, we obtained biochemical parameters at baseline and at 12 weeks after finishing the treatment. Results: We obtained 30 patients with paired CV risk assessment, before and after the treatment. At baseline, 45.5% (10/22) of patients showed pathological ABI, decreasing up to 27.3% (6/22) at week 12 (p=ns). We also found an improvement in CIMT; 12% (3/25) at baseline vs. 8% (2/25) at week 12 showed a pathological CIMT. Combining both tests, 60% (12/20) of patients showed pathological CIMT or ABI at baseline and this value decreased to 35% (7/20) at week 12 (p=ns) Patients who responded to the treatment, in terms of CV risk, had a worse baseline profile of soluble biomarkers (Table). Conclusion: These preliminary results (ongoing study) showed that patients with basal pro‐atherogenic conditions had a greater improvement in cardiovascular risk assessed by ankle‐brachial index and carotid intima‐media thickness.

Baseline Characteristics

Data are shown as mean ± SD. variables were analyzed with Mann‐Whitney U tests.

Disclosures:

The following people have nothing to disclose: Rocío Muñoz, Javier Ampuero, Raquel Millan, Maria del Carmen Rico, Mercedes Romera, Carlota Jimeno, Antonio Gil‐Gómez, Manuel Romero‐Gomez

Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University School of Medicine, Toyoake, Japan

Background and Aim: Liver stiffness (LS) by transient elastography (TE) and velocity of shear wave (Vs) by acoustic radiation force impulse (ARFI) have been reported to correlate with fibrosis stages in various liver diseases. The aim of the present study was to evaluate the effect of direct‐acting antivirals (DAAs) on LS and Vs in chronic hepatitis C (CHC). Methods: LS (kPa) and Vs (m/s) were measured in 582 patients with CHC. The changes of LS and Vs were assessed in 300 patients treated with DAAs. 125 patients were treated with daclatasvir (DCV) and asunaprevir (ASV), 115 with sofosbuvir (SOF) and ledipasvir (LDV) for HCV genotype 1, and 60 with SOF and ribavirin (RBV) for genotype 2. Results: DCV/ASV, SOF/LDV, SOF/RBV treatments achieved high rates of sustained virologic response (SVR) (89, 95, 97%, respectively). LS significantly decreased and Vs did not significantly decrease at end of treatment (EOT) (10.0, p=0.0005; 1.76, p=0.11), LS and Vs significantly decreased at 6 months after EOT (10.3, p<0.0001; 1.69, p<0.0001) and at 12 months after EOT (12.3, p=0.0034; 1.98, p=0.0062), compared with baseline (12.7, 1.86) in patients with DCV/ASV. LS decreased in tendency (10.2, p=0.081) but Vs did not significantly decrease (1.62) at EOT compared with baseline (12.0, 1.60) in patients with SOF/ LDV. LS significantly decreased (10.0, p=0.0097) but Vs did not significantly decrease (1.75) at 6 months after EOT compared with baseline (11.1, 1.63) in patients with SOF/RBV. Fibrosis stages were deduced from Vs values according to cut‐off values for fibrosis stages in patients with DCV/ASV The cutoff values determined by ROC analysis were 1.28 for F2, 1.44 for F3, and 1.73 for F4 in 108 patients who underwent liver biopsy Two points or greater reduction of deduced stage was observed in 19% of patients with DCV/ASV, whose pretreatment deduced stages were F3‐F4 Higher platelets counts, lower total bilirubin levels, and lower gamma globulin levels were significantly associated with a 2‐point or greater reduction of deduced fibrosis stage. LS and Vs at baseline did not predict SVR in each treatment. Conclusions: The reduction of LS was observed in patients with DAAs, and can be attributed to regression of liver fibrosis and inflammation. The reduction of Vs was slower than that of LS. This finding may be attributed to the stronger association of LS with inflammation compared with that of Vs. The significant reduction of deduced fibrosis stage was observed in those with milder fibrosis which was indicated by higher platelets counts, lower total bilirubin levels and gamma globulin levels. TE and ARFI were useful for evaluating the effect of DAAs in CHC.

Disclosures:

Kentaro Yoshioka ‐ Consulting: Sanwa Kagaku KK

The following people have nothing to disclose: Naoto Kawabe, Toshiki Kan, Tomoki Takamura, Sayuri Nomura, Senju Hashimoto, Michihito Murao, Takuji Nakano, Kazunori Nakaoka, Masashi Ohki, Ochi Yuka, Takamitsu Kurashita, Aiko Fukui, Toru Nishikawa, Keisuke Osakabe, Naohiro Ichino

¹Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; ²Odense Drug Treatment Center, Odense, Denmark; ³Department of Clinical Immunology, Odense University Hospital, Odense, Denmark; ⁴Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark

Background and aims People who inject drugs (PWID) are the driving force of chronic hepatitis C (CHC) in the western world, but treatment uptake has been low in. Direct acting antivirals (DAA's) cures more than 90% of patients. Outreach treatment programs at drug treatment centers (DTC's) are feasible but shorter treatment duration is desirable. Four week DAA trials have been disappointing so far. We hypothesise that maintaining ribavirin (RBV) in a 4 week DAA regimen and adding pegylated‐interferon 2 alpha(PEG 2a) could give high cure rates in drug users. Method The study was conducted at one DTC. Thirty two patients were randomized 1:1 to either LDV/SOF+RBV or LDV/SOF/RBV+PEG 2a for 4 weeks. RBV was dosed weight based and PEG 2a at 180 ug weekly. Main inclusion criteria: Treatment naïve patient with CHC (all genotypes), in opium substitution therapy(OST) p, age< 50 years, weight<100 kg, viral load<2mill lU/ml and liver stiffness measure(LSM)< 8 kPa. Subjects were allowed any kind of concomitant drug or alcohol use but should be compliant to their OST program. Primary endpoint was sustained virological response at week 12 after end of treatment (SVR 12) in the intention to treat (ITT) population. Results Forty seven persons were screened, and 32 initiated treatment. At date of submission SVR 12 in the ITT population was 92 % (12/13) in the interferon arm and 77% (10/13) in the interferon free arm. One virological relaps was detected. The remaining three failures were due to lost to follow‐up or premature withdrawel from therapy. The PP SVR12 is so far 100% in the interferon arm and 91% in the interferon free arm. Full SVR 12 data will be presented at the meeting. Conclusion 4 weeks of sofosbuvir, ledipasvir and ribavirin with or without interferon was highly effective in curing CHC in this hard to reach but easy to treat population of non‐cirrhotic drug users on OST with only one virological relapse detected in a PP patient. Delivering treatment at a DTC concurrently with OST was feasible and the SVR rates suggest this short regiment to be evaluated in larger trials.

Disclosures:

Anne L. Øvrehus ‐ Advisory Committees or Review Panels: Gilead Sciences, Abbvie; Grant/Research Support: Gilead Sciences; Speaking and Teaching: BMS

Peer B. Christensen ‐ Advisory Committees or Review Panels: Roche; Grant/ Research Support: Abbvie, Gilead, Merck Sharp & Dohme, Roche, Scheering, MSD

The following people have nothing to disclose: Inge Birkemose, Dorte Kinggaard Holm, Belinda K. Moessner, Henrik Krarup

¹Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA; ²San Jose Gastroenterology, San Jose, CA; ³Digestive Health Associates of Texas, Plano, TX; ⁴Liver and Digestive Consultants, Houston, TX

Background: HCV affects approximately 30 million persons in Southeast Asia where HCV‐6 is one of the most prevalent genotypes. Treatment data is limited for HCV‐6, especially with new direct acting antiviral (DAA) agents. LDV/SOF FDC for 12 weeks has been shown to be effective for multiple HCV genotypes including treatment‐naïve HCV‐6. Our goal is to examine treatment outcomes in a diverse HCV‐6 population. Methods: We prospectively enrolled 60 HCV‐6 patients at four medical centers in California and Texas, USA. All patients received LDV 90mg/SOF 400 mg in a single tablet regimen orally once a day for 8 weeks if they were treatment‐naive and did not have cirrhosis or for 12 weeks if they had cirrhosis (treatment‐naive and experienced) or treatment‐experienced (cirrhosis and noncirrhosis) Patients with prior solid organ transplantation were excluded Primary outcome was sustained virological response 12 weeks after therapy (SVR12). Secondary outcomes were adverse events (AE). All patients gave written consent. Results: Overall mean age was 58±10 and 58% were male. All patients were Asian and foreign‐born The 8‐week group included 20 patients (33.3%) and the 12‐week included 40 patients (66.7%). There were no statistically significant differences in baseline clinical and laboratory characteristics other than cirrhosis status and prior treatment history between the two groups. Baseline HCV RNA level was 6.43±0.73 log IU/ mL and the distribution of HCV‐6 subtypes were 23% HCV‐ 6a/b, 37% HCV‐6c, and 4% HCV‐6m. Baseline platelet count was 191±67 overall, 208±53 for 8‐week group and 182±73 for the 12‐week group (p=0.16). There were two patients with decompensation (5.0%), 3 patients with liver cancer (7.5%), and 14 with prior treatment (35.0%) in the 12‐week group Currently, SVR12 were available for 59 patients (of 60). SVR12 was 95.0% for the 8‐week group (19/20) and 94.9% for the 12‐week group (37/39). All patients completed the intended treatment duration. There were two treatment‐unrelated SAEs (H. pylori‐related bleeding gastric ulcer and leg fracture due to mechanical fall), and both patients achieved SVR12. AEs included fatigue (5%), insomnia (3%), headache (1.7%), and nausea (1.7%). Conclusion: In this largest clinical trial of HCV‐6 to date with LDV/SOF FDC orally once daily or with DAAs in general, LDV/SOF FDC for 8 weeks was safe and effective for patients without cirrhosis or prior treatment failure (SVR12=95.0%), and LDV/SOF FDC for 12 weeks was also safe and effective for patients with cirrhosis and/or prior treatment failure, including patients with hepatic decompensation and liver cancer (SVR 12=94.9%).

Disclosures:

Mindie H. Nguyen ‐ Advisory Committees or Review Panels: Bristol‐Myers Squibb, Gilead; Consulting: Gilead Sciences, Inc. ; Grant/Research Support: Gilead Sciences, Inc., Bristol‐Myers Squibb

Huy N. Trinh ‐ Grant/Research Support: Gilead, Intercept, Abbvie, merk; Speaking and Teaching: Gilead; Stock Shareholder: Gilead

Son T. Do ‐ Advisory Committees or Review Panels: gilead, Asian Health Foundation; Speaking and Teaching: gilead, Asian Health Foundation

Thuan Nguyen ‐ Speaking and Teaching: Gilead, Abbvie

Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, Queens, NY

Background New York City (NYC) Health Department has an established Care Coordination Protocol and Heath Promotion Manual for HIV‐infected persons. Infection with the Hepatitis C Virus (HCV) is a complex disease often occurring in patients with substance abuse, HIV, and mental illness, making treatment in a supported setting critical. Project INSPIRE, a Round II Healthcare Innovation Award from the Centers for Medicaid and Medicare Services, was designed by the Health Department to implement and test a comprehensive care coordination protocol and health promotion curriculum adapted from HIV and tailored for HCV Primary Aim To demonstrate a model of service delivery and payment that can reduce morbidity and death from chronic illnesses and reduce costs associated with its complications, using chronic HCV infection as a case study. Methods Established care coordination protocols and health promotion materials used for HIV/AIDS were adapted for use with patients with HCV infection with the overall goal of improving HCV cure rates and patient self‐sufficiency. The protocol includes: comprehensive assessment, care plan, health promotion, treatment readiness counseling, alcohol and drug counseling and medication adherance support. Health promotion sessions are designed to provide information on HCV infection, treatment for HCV, liver health, alcohol and drug use, and how to avoid re‐infection. A robust monitoring and evaluation framework is being used to evaluate the program including monthly data feedback reports, fidelity analysis, clinical outcomes analysis, comparison with a control group, and cost analysis Results INSPIRE was implemented at 12 outpatient clinics, serving high need patients, with a high level of fidelity to the protocol. Among the 1,805 participants enrolled by April 30, 2016, most reached key milestones within 30 days of enrollment including completing a comprehensive assessment (83%), attending their first clinical appointment for HCV care (90%), and receiving a medical evaluation (79%) Over 95% of participants who initiated treatment have received alcohol counseling, health promotion, treatment readiness counseling, and medication coordination Two‐thirds (66%) of participants received their first health promotion session within 15 days of enrollment. The project was implemented at two major medical centers, and starting many on treatment with the expectation that the vast majority will be cured. Over the next year, a plan to disseminate the care coordination protocol and health promotion materials will be developed and the costs of care coordination will be calculated and integrated into a payment model.

Disclosures:

The following people have nothing to disclose: Marie P. Bresnahan, Mary Ford, Payal Desai, Nicolette G. Gantt, Fabienne Laraque