Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment a prospective cohort study

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Carrat, Fabrice | Fontaine, Hélène | Dorival, Céline | Simony, Mélanie | Diallo, Alpha | Hezode, Christophe | de Ledinghen, Victor | Larrey, Dominique | Haour, Georges | Bronowicki, Jean-Pierre | Zoulim, Fabien | Asselah, Tarik | Marcellin, Patrick | Thabut, Dominique | Leroy, Vincent | Tran, Albert | Habersetzer, François | Samuel, Didier | Guyader, Dominique | Chazouilleres, Olivier | Mathurin, Philippe | Metivier, Sophie | Alric, Laurent | Riachi, Ghassan | Gournay, Jérôme | Abergel, Armand | Calès, Paul | Ganne, Nathalie | Loustaud-Ratti, Véronique | d'Alteroche, Louis | Causse, Xavier | Geist, Claire | Minello, Anne | Rosa, Isabelle | Gelu-Simeon, Moana | Portal, Isabelle | Raffi, François | Bourlière, Marc | Pol, Stanislas

Edité par CCSD ; Elsevier -

International audience. Background: Although direct-acting antivirals have been used extensively to treat patients with chronic hepatitis C virus (HCV) infection, their clinical effectiveness has not been well reported. We compared the incidence of death, hepatocellular carcinoma, and decompensated cirrhosis between patients treated with direct-acting antivirals and those untreated, in the French ANRS CO22 Hepather cohort.Methods: We did a prospective study in adult patients with chronic HCV infection enrolled from 32 expert hepatology centres in France. We excluded patients with chronic hepatitis B, those with a history of decompensated cirrhosis, hepatocellular carcinoma, or liver transplantation, and patients who were treated with interferon-ribavirin with or without first-generation protease inhibitors. Co-primary study outcomes were incidence of all-cause mortality, hepatocellular carcinoma, and decompensated cirrhosis. The association between direct-acting antivirals and these outcomes was quantified using time-dependent Cox proportional hazards models. This study is registered with ClinicalTrials.gov, number NCT01953458.Findings: Between Aug 6, 2012, and Dec 31, 2015, 10 166 patients were eligible for the study. 9895 (97%) patients had available follow-up information and were included in analyses. Median follow-up was 33·4 months (IQR 24·0-40·7). Treatment with direct-acting antivirals was initiated during follow-up in 7344 patients, and 2551 patients remained untreated at the final follow-up visit. During follow-up, 218 patients died (129 treated, 89 untreated), 258 reported hepatocellular carcinoma (187 treated, 71 untreated), and 106 had decompensated cirrhosis (74 treated, 32 untreated). Exposure to direct-acting antivirals was associated with increased risk for hepatocellular carcinoma (unadjusted hazard ratio [HR] 2·77, 95% CI 2·07-3·71) and decompensated cirrhosis (3·83, 2·29-6·42). After adjustment for variables (age, sex, body-mass index, geographical origin, infection route, fibrosis score, HCV treatment-naive, HCV genotype, alcohol consumption, diabetes, arterial hypertension, biological variables, and model for end-stage liver disease score in patients with cirrhosis), exposure to direct-acting antivirals was associated with a decrease in all-cause mortality (adjusted HR 0·48, 95% CI 0·33-0·70) and hepatocellular carcinoma (0·66, 0·46-0·93), and was not associated with decompensated cirrhosis (1·14, 0·57-2·27).Interpretation: Treatment with direct-acting antivirals is associated with reduced risk for mortality and hepatocellular carcinoma and should be considered in all patients with chronic HCV infection.

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