Clinical outcome after SVR: ANRS CO22 HEPATHER Design Observational prospective cohort (France) 12 502 HCV-infected patients Exclusion criteria: HBV co-infection, history of decompensated cirrhosis, HCC or liver transplant, treatment with IFN-RBV ± 1st generation PI, no follow-up Survival time since enrolment or start of DAA (censoring date: July 1st, 2017, or death, or HCC, or decompensated cirrhosis) Cox proportional hazards models with Inverse Probability of Treatment Weighting (IPTW) to quantify the impact of DAA (as a time dependent-covariate) on clinical outcomes IPTW scores were obtained from a logistic model linking treatment with baseline covariates that confounded the treatment-outcome relationship Study population 6 460 patients received DAA 8 462 patient-years of follow up, occurrence of 90 deaths, 164 HCC and 77 decompensation 2 835 patients did not receive DAA 10 040 patient-years of follow up, occurrence of 78 deaths, 57 HCC and 35 decompensation ANRS CO22 HEPATHER Carrat F, AASLD 2017, Abs. LB-28

Clinical outcome after SVR: ANRS CO22 HEPATHER Baseline characteristics Median (IQR) age: 56 (50-65) years Male: 54% Cirrhosis: 38% Treatment experienced: 54% Genotype 1: 66% 2: 7% 3: 11% 4: 12% Diabetes: 12% BMI ≥ 30 kg/m2: 13% Hypertension: 29% Association of baseline characteristics and DAA treatment during follow-up (multivariate analysis) More likely to start DAA if Age > 50 years Genotype 3 (vs genotype 1) Fibrosis F3-F4 (vs F0-F1) Less likely to start DAA if Female Genotype 2 (vs genotype 1) Treatment naive ANRS CO22 HEPATHER Carrat F, AASLD 2017, Abs. LB-28

Clinical outcome after SVR: ANRS CO22 HEPATHER All-cause-deaths Weighted survival (IPTW) 1.00 0.98 DAA - DAA + Deaths DAA - : 78 vs DAA + : 90 0.96 0.94 HRIPWfixed for DAA+ 0.65 (0.45;0.95), p=0.0258 0.92 0.90 5 10 15 20 25 30 Months Hepatocellular carcinoma Weighted survival (IPTW) Decompensated cirrhosis Weighted survival (IPTW) 1.00 1.00 0.98 0.98 0.96 0.96 HRIPWfixed for DAA+ 0.90 (0.58;1.41), p=0.6533 0.94 0.94 HRIPWfixed for DAA+ 1.19 (0.85;1.66), p=0.3178 0.92 0.92 0.90 0.90 5 10 15 20 25 30 5 10 15 20 25 30 Months Months HCC = DAA - : 57 vs DAA + : 164 Decompensation = DAA - : 35 vs DAA + : 77 ANRS CO22 HEPATHER Carrat F, AASLD 2017, Abs. LB-28

Clinical outcome after SVR: ANRS CO22 HEPATHER HRcrude (DAA+ vs DAA-) HRIPWfixed (DAA+ vs DAA-) 2,43 Liver related deaths (n = 58) 0,68 1,23 Non liver related deaths (n = 81) 0,75 1,53 All cause deaths (n = 168)* 0,65 0,1 1 10 * 29 deaths were not yet adjudicated ANRS CO22 HEPATHER Carrat F, AASLD 2017, Abs. LB-28

Clinical outcome after SVR: ANRS CO22 HEPATHER Conclusions DAA was associated with a decreased risk of death The decrease in deaths was more pronounced for liver-related deaths than for non liver-related deaths and no increased risk of HCC and decompensation ANRS CO22 HEPATHER Carrat F, AASLD 2017, Abs. LB-28