P1165 STANDARD INTERFERON – DOWN BUT NOT OUT

POSTERS P1163 ALL-ORAL THERAPY WITH DACLATASVIR IN COMBINATION WITH ASUNAPREVIR AND BMS-791325 FOR TREATMENT-NAIVE PATIENTS WITH CHRONIC HCV GENOTYPE 4 INFECTION T. Hassanein1 , K. Sims2 , M. Bennett3 , N. Gitlin4 , E. Lawitz5 , T. Nguyen6 , L. Webster7 , Z. Younossi8 , H. Schwartz9 , P.J. Thuluvath10 , H. Zhou11 , B. Rege2 , F. McPhee12 , N. Zhou12 , M. Wind-Rotolo11 , E. Chung2 , A. Griffies2 , D. Grasela2 , D.F. Gardiner2 . 1 Southern California Liver Centers, Coronado, CA, 2 Research and Development, Bristol-Myers Squibb, Hopewell, NJ, 3 Medical Associates Research Group, San Diego, CA, 4 Atlanta Gastroenterology Associates, Atlanta, GA, 5 The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, 6 Research and Education Inc, San Diego, CA, 7 CRI Lifetree, Salt Lake City, UT, 8 Inova Fairfax Hospital, Center for Liver Diseases, Falls Church, VA, 9 Miami Research Associates, South Miami, FL, 10 Mercy Medical Center, Baltimore, MD, 11 Research and Development, Bristol-Myers Squibb, Princeton, NJ, 12 Research and Development, Bristol-Myers Squibb, Wallingford, CT, United States E-mail: [email protected] Background and Aims: The all-oral, ribavirin-free combination of daclatasvir (DCV; NS5A inhibitor), asunaprevir (ASV; NS3 inhibitor), and BMS-791325 (’325; non-nucleoside NS5B inhibitor) achieved sustained virologic response (SVR12 ) in 92% of patients with chronic HCV genotype (GT)1 infection. This regimen has now been evaluated in patients with GT4 infection in a study expansion (AI443–014). Methods: Treatment-naïve, HCV GT4-infected patients were randomly assigned (1:1) to receive a twice-daily regimen of DCV 30 mg, ASV 200 mg, and ’325 75 mg (n = 11) or 150 mg (n = 10) for 12 weeks. Results: Baseline characteristics were comparable across groups; overall, patients were 62% male, 91% white, non-cirrhotic, and 71% IL28B non-CC. All patients completed 12 weeks of therapy. HCV RNA was undetectable in 21/21 (100%) patients at the end of treatment. SVR at posttreatment week 12 (SVR12 ) was achieved by 10/11 patients in the ’325 75 mg group (mITT analysis; 1 missing patient achieved SVR24 ) and 9/10 patients in the ’325 150 mg group (1 missing patient remains in follow-up). There were no on-treatment virologic failures or posttreatment relapses. There were no serious adverse events (AEs), grade 3/4 AEs, or grade 3/4 liver-related lab abnormalities. The most frequent AEs were headache (29%), insomnia (19%), nausea (14%), and pain (14%). Conclusions: Twelve weeks of all-oral treatment with DCV+ASV+BMS-791325 achieved SVR12 in all patients with observed posttreatment data, with no virologic failures. These results extend the potent antiviral activity of this interferon- and ribavirin-free regimen to patients with HCV GT4 infection, while maintaining the positive tolerability and safety profile documented previously in GT1 patients. P1164 THE DISEASE BURDEN OF CHRONIC HEPATITIS C VIRUS (HCV) INFECTION IN EGYPT: FUTURE IMPACT OF VARYING TREATMENT STRATEGIES I. Waked1 , W. Doss2,3 , M. El-Sayed4 , C. Estes5 , H. Razavi5 , G. Shiha6 , A. Yosry2 , G. Esmat2 . 1 Hepatology, National Liver Institute, Shebeel El Kom, 2 Hepatology and Tropical Medicine, Cairo University, 3 National Hepatology and Tropical Medicine Research Institute, 4 Pediatrics, Ain Shams University, Cairo, Egypt; 5 Center for Disease Analysis (CDA), Louisville, CO, United States; 6 Medicine, Mansoura University, Mansoura, Egypt E-mail: [email protected] Background and Aims: Egypt has one of the largest HCV infected populations in the world, with HCV the major cause of cirrhosis, S472

hepatocellular carcinoma (HCC), and liver transplantation. The future proportions of the epidemic have not been accurately projected. Methods: We used a modeling approach to examine the HCV-infected population and disease progression in Egypt. We modeled 36 hypothetical, age- and gender-defined cohorts to define incidence, prevalence, complications, and mortality. Baseline assumptions and transition probabilities were extracted from the literature. We examined different strategies of reducing new infections and increasing treatment and SVR. Results: 175,300 New HCV infections occurred in Egypt in 2012. The viremic prevalence is estimated to have peaked in 2006 (6,387,000 individuals) and will decline by 23.5% by 2030 (4,887,000 individuals). However, the number of cases of compensated (n = 813,900) and decompensated (n = 74,620) cirrhosis, HCC (n = 17,220), and liver-related deaths (n = 27,050) will peak as late as 2030. A strategy was modeled where treated cases increased 200% in 2014, then 250% in 2016 and 2018, reaching 755,720 in 2020 as compared to 60,460 in 2013, with SVR increased to 90% and treatment eligibility to 80% (age 15–69 years, fibrosis ≥F0). Compared to base case, this strategy decreased prevalent infections by 4,529,700 (93%) liver-related deaths by 193,100 (80%) and HCV-related HCC and decompensated cirrhosis by 83% by 2030. Conclusions: Extraordinary measures are necessary in Egypt to substantially reduce cases of advanced liver disease which continue to rise. This study will facilitate disease forecasting, resource planning, and rational strategies for HCV management in Egypt.

P1165 STANDARD INTERFERON – DOWN BUT NOT OUT A.A. Choudhry1 , A. Alam2 , A.A. Nawaz3 , M. Riaz3 , I. Yousaf3 , A. Alvi3 . 1 Gujranwala Liver Foundation, Gujranwala, 2 Sheikh Zayed Hospital, 3 Fatima Memorial Hospital, Lahore, Pakistan E-mail: [email protected] Background and Aims: HCV affects 5% of the population in Pakistan. The high cost of antiviral therapy is the main obstacle to treatment in 3rd world countries. We studied efficacy of standard interferon/ribavirin [Rs. 37,802.00 (US$353.00)] and pegylated interferon/ribavirin [Rs. 152,000.00 (US$1419.00)] in treatmentnaive GT3 patients. RVR as a predictor of SVR was evaluated for both. Methods: Retrospective analysis of data of GT3 treatmentnaive patients treated with standard interferon a-2b, pegylated interferon a-2a&2b and ribavirin. Inclusion criteria; age 18 to 65 years, detectable viral load, genotype 3, Childs’ score <7 and HBsAg-negative. HCV RNA by PCR qualitative (QL) was checked at week 4. RVR-positive patients received 24 week therapy and HCV RNA (QL) repeated at end of treatment and 6 months after completion. RVR-negative patients’ HCV RNA by PCR quantitative (QN) checked at week 12. Antiviral therapy continued in patients with cEVR and pEVR and ETR checked at week 24. Therapy was discontinued in patients with negative ETR. In ETRpositive patients, antiviral therapy stopped at week 24 in patients who had favorable predictors of response while patients with poor predictors of response were assigned to 48 weeks’ treatment. Data was analyzed in SPSS version 17.0. p value was calculated using chi-square test. Results: See the table. RVR-positive patients did significantly better (p < 0.0001) for both types of interferon. Conclusions: Standard IFN is an excellent and cost-effective option in treatment naiive GT3 patients with RVR. In RVR-negative patients there is a case for early switch to pegylated interferon.

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POSTERS Table: Therapy results in treatment-naive genotype 3 patients

Standard interferon/ribavirin (N = 269) Total no. of patients SVR Relapser Non Responder Pegylated interferon/ribavirin (N = 86) Total no. of patients SVR Relapser Non Responder

RVR-Pos

RVR-Neg

171 (63.5%) 132 (77.2%) 39 (22.8%) 0 (0%)

98 (36.5%) 17 (17.3%) 17 (17.3%) 64 (65.4%)

60 (69.8%) 50 (83.3%) 10 (16.7%) 0 (0%)

26 (30.2%) 11 (42.3%) 9 (34.6%) 6 (23.1%)

P1166 FACTORS ASSOCIATED WITH HCV TREATMENT INITIATION IN DRUG USERS FOLLOWED IN A CARE CENTER FOR ADDICTS G. Ouziel, P. Pradat, P. Lack, F. Zoulim, F. Bailly, O. Lejeune. Hepatology Department, Hospices Civils de Lyon, Lyon, France E-mail: [email protected] Background and Aims: Prevalence and incidence of HCV infection among injection drug users (IDU) remains high. However, treatment is rarely initiated because of comorbid psychiatric conditions, social precarity, risk of poor compliance or reinfection. We aimed to identify factors that possibly influence clinicians for initiating HCV treatment. Methods: This is a single center retrospective study analyzing chronic HCV patients followed in a care center for drug users (CSAPA) in Lyon, France, in 2012. We compared social, psychiatric, addictive, and clinical characteristics between untreated patients and patients for whom PEG-IFN/ribavirin therapy was initiated. Results: One hundred and twenty-three HCV infected patients (82% males, mean age 43 years) were analyzed. Sixty-seven (54%) received HCV treatment. Thirty-six percent of patients with active drug injection received therapy vs 63% of patients without such practice (p = 0.009). Patients in remission for drug addiction were more often treated compared with patients with active addiction (69% vs 43%; p = 0.005). Treatment was more often initiated in heroin users than among morphine or buprenorphine injectors (62% vs 39%; p = 0.022). No association was observed between social (housing, income, work) or psychiatric (depressive or psychotic pathology) characteristics and treatment initiation. Viral genotype and liver fibrosis did not impact treatment decision. HIV-coinfection was associated with lower treatment initiation (27% vs 58%, respectively; p = 0.047). Conclusions: Our results stress the importance of addiction management and injection behavior on HCV treatment decision. Psychiatric pathologies and precarity do not seem to influence clinician’s decision. Altogether this underscores the need to manage HCV infected IDU in centers specialized in both addiction and hepatology. P1167 rs12979860 IL28B GENOTYPE IS ASSOCIATED WITH ADVANCED FIBROSIS IN HCV GENOTYPE 1-INFECTED EUROPEAN PATIENTS WITH CHRONIC HEPATITIS C: RESULTS FROM THE INTERNATIONAL GEN-C STUDY 1

2

3

4

5

A. Mangia , V. De Ledinghen , F. Bailly , J. Brahm , J. Keiss , J. Valantinas6 , N. Rasmann7 , G. Riachi8 , D. Messinger9 , A. Caputo10 , G.R. Foster11 , on behalf of the Gen-C Study Group. 1 Liver Unit, IRCCS Hospital ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy; 2 Hepatology Unit, Hˆ opital Haut-L´evˆeque, CHU Bordeaux, Pessac, 3 Hepatology Unit, Groupe Hospitalier Nord, CHU Lyon, France; 4 Gastroenterology Department, University of Chile Clinical Hospital, Santiago, Chile; 5 Infectology Center of Latvia, Riga Eastern Clinical University Hospital, Riga, Latvia; 6 Vilnius University, Vilnius, Lithuania; 7 Center for Infectious Diseases, Tallinn, Estonia;

8 Hepatology Unit, Charles Nicolle Hospital, Rouen, France; 9 IST GmbH, Mannheim, Germany; 10 F. Hoffmann-La Roche Ltd, Basel, Switzerland; 11 Queen Mary University of London, Institute of Cellular and Molecular Sciences, London, United Kingdom E-mail: [email protected]

Background and Aims: Host IL28B genotype influences spontaneous clearance of acute HCV infection and response to interferon-based treatment in patients with chronic hepatitis C (CHC). Whether IL28B genotype influences progression of hepatic fibrosis is unclear. The large prospective international Gen-C study was designed to evaluate relationships between IL28B genotypes and fibrosis stage in patients with CHC. Methods: In this analysis of data from treatment-naive HCV genotype (G)1-infected Caucasian patients without autoimmune disease, associations between patient characteristics and IL28B rs12979860 genotype were explored by multiple logistic regression (MLR) analysis. A diagnosis of cirrhosis or transition to cirrhosis was made, at the discretion of the investigator, by biopsy or noninvasive method. Results: Among 1147 patients, enrolled from 15 European countries, 53% were male, the mean age was 47 (±13) years, 32% (n = 366) had a CC genotype, 53% (n = 613) had a CT genotype and 15% (n = 168) had a TT genotype. Baseline fibrosis assessment (biopsy or noninvasive) was available for 1099 (95.8%) patients. Among patients with IL28B CC, CT and TT genotypes, 20% (69/348), 25% (145/592) and 33% (53/159), respectively, had cirrhosis/transition to fibrosis (Cochran-Armitage trend test p = 0.0014). FibroScan values (n = 507) had a significant association with IL28B (mean score: CC 9.49; CT 10.3; TT 12.7 kPa; Cochran-Armitage trend test p = 0.0224). Factors significantly associated with cirrhosis/transition to cirrhosis in the final MLR model are shown in the table. Table: Multiple logistic regression analysis for cirrhosis/transition to cirrhosis Factor rs12979850 IL28B* CT vs. CC TT vs. CC Age, per 10-year increment BMI, per 1 kg/m2 increment AST ratio, per 1 unit increment Platelets, per 1×107 /L decrement

Odds ratio (95% confidence interval)

p-value

1.21 (0.82–1.77) 2.04 (1.24–3.35) 1.58 (1.37–1.83) 1.09 (1.05–1.14) 1.43 (1.24–1.65) 3.30 (2.29–4.74)

0.3321 0.0047 <0.0001 <0.0001 <0.0001 <0.0001

Factors included in the backward elimination procedure (p-value = 0.05 to remain in model): IL28B, age, gender, body weight, BMI, HCV RNA, years since HCV infection, ALT ratio, AST ratio, platelets, current regular alcohol use (yes/no), drug use (other/never). *p = 0.0163 for selection of IL28B (Wald Chi-Square test with two degrees of freedom).

Conclusions: This analysis demonstrates that rs12979860 IL28B genotype is significantly associated with advanced fibrosis in European patients with HCV G1 infection after adjustment for other prognostic factors. Funded by Roche. P1168 ITPA AND SLC29A1 GENOTYPING BEFORE TRIPLE THERAPY PREDICT SEVERITY OF RIBAVIRIN-INDUCED ANEMIA L. Milazzo1 , S. Landonio2 , C. Magni2 , C. Gervasoni1 , E. Calvi1 , S. Cheli3 , E. Clementi3 , M. Galli1 , F.S. Falvella3 . 1 Department of Biomedical and Clinical Sciences Luigi Sacco, Universit` a degli Studi di Milano, 2 I Unit of Infectious Diseases, 3 Unit of Clinical Pharmacology, L. Sacco University Hospital, Milan, Italy E-mail: [email protected] Background and Aims: Inosine triphosphatase (ITPA) gene singlenucleotide polymorphisms (SNPs) rs1127354 (C/A) and rs7270101

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