1. Kwo PY. NEJM 2014;371:2375-82 CORAL-I  Design OBV/PTV/r + DSV + RBV Open label Phase II 18-70 years Chronic HCV infection, genotype 1 Liver transplantation for HCV ≥ 12 months ago HCV RNA > 10,000 IU/ml Treatment naïve or prior IFN-based regimen prior to transplantation Metavir ≤ F2 by biopsy No HBV or HIV coinfection CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection W24 N = 34 Stable immunosuppressive therapy : tacrolimus or cyclosporin ; glucocorticoïds at dose ≤ 5 mg/day permitted  Treatment regimens –Co-formulated ombitasvir/paritaprevir/rironavir/ (OBV/PTV/r/): 25/150/100 mg qd = 2 tablets –Dasabuvir (DSV) : 250 mg bid –RBV : dose selected by investigator (most often 600-800 mg/day)  Objective –SVR 12, by intention to treat, with 95% CI, descriptive analysis

2. N = 34 Demographics and clinical characteristics Mean age, years60 Female31% Genotype 1a85% IL28B CC genotype24% HCV RNA log 10 IU/ml, mean (SD) 6.6 ± 0.5 Metavir F0 / F1 / F2, %18% / 38% / 44% Lack of response to previous IFN treatment71% Time since liver transplantation, months, median39.5 Tacrolimus / ciclosporine, %85% / 15% Outcome, % (95% CI) HCV RNA < 25 IU/ml at W24 (end of treatment)100% (90-100) SVR 12 (HCV RNA < 25 IU/ml)97% (85-100) Relapse, n, %1*, 3% Baseline characteristics and treatment response * At relapse : resistance-associated variants R155K in NS3, M28T and Q30R in NS5A, and G554S in NS5B Kwo PY. NEJM 2014;371:2375-82 CORAL-I CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

3. AE leading to discontinuation1 (3%)* Serious adverse events2 (6%) Fatigue50% Headache44% Cough32% Anemia29% Diarrhea26% Insomnia26% Asthenia24% Nausea24% Muscle spasms21% Back pain18% Dizziness18% Peripheral edema18% Rhinorrhea18% Adverse events and laboratory abnormalities in the 34 patients, N (%) Grade 3 laboratory abnormalities ALT0 AST0 Total bilirubin2 (6%) Hemoglobin1 (3%) Creatinine0 * W18 : rash, memory impairment, and anxiety. SVR 12 despite premature discontinuation No graft rejection and no deaths Kwo PY. NEJM 2014;371:2375-82 CORAL-I CORAL Study: OBV/PTV/r + DSV + RBV in liver transplantation with recurrent genotype 1 infection

4.  Summary –In this phase II trial of a 24-week, IFN-free, all-oral antiviral regimen for HCV genotype 1 infection, a rate of sustained virologic response of 97% (95% CI, 85 to 100) at post-treatment weeks 12 and 24 was observed among liver-transplant recipients with no fibrosis or mild fibrosis. –No deaths or episodes of graft rejection –Very good tolerability and safety –No patient needed a blood transfusion ; 5 patients (15%) required erythropoietin, all of whom had initially received RBV at a total daily dose of 1000 or 1200 mg Given the high SVR 12, regardless of the initial RBV dose, an initial dose of 600 to 800 mg may provide sufficient therapeutic benefit and minimize the risk of severe anemia –Limitations Patients with advanced fibrosis excluded Patients with aggressive forms of recurrent HCV infection (e.g., fibrosing cholestatic hepatitis) excluded Kwo PY. NEJM 2014;371:2375-82 CORAL-I