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Blaise K Kutala,1,2 Feryel Mouri,1 Corinne Castelnau,1 Valerie Bouton,1 Nathalie Giuily,1 Nathalie Boyer,1 Tarik Asselah,1,2 Patrick Marcellin1,2 1Service d’hépatologie, Hopital Beaujon-APHP, 2INSERM – University of Paris Diderot, Paris, France Background: The combination of sofosbuvir (SOF) with ribavirin (RBV) or daclatasvir (DCV) or simeprevir (SIM) for the treatment of patients infected by chronic hepatitis C (CHC) have led to significantly increased rates of sustained virological response (SVR). However, there is only limited data regarding factors associated with treatment failure in a “real-life” cohort. Patients and methods: Consecutive treatment-naive and treatment-experienced patients F3–F4 were treated with SOF-based interferon-free therapy in our hospital from November 2013 to July 2015. The primary endpoint was the proportion of patients with sustained virological response 12 weeks after cessation of therapy (SVR12). Results: A total of 167 treatment-naive and 207 treatment-experienced patients were treated and followed up for 2 years (n=383). Overall, 71% were men; among them, 54% had cirrhosis and the median age was 53 years. SVR12 was achieved by 82% of the patients receiving SOF+RBV, 92% receiving SOF+DCV, and 79% receiving SOF+SIM. Metavir F4 and albumin serum were found as independent risk factors associated with treatment failure in groups receiving SOF+RBV (p=0.008 and p=0.001), SOF+DCV (p=0.038 and p=0.043), and SOF+SIM±RBV (p=0.014 and p=0.017), respectively. The most common adverse events were fatigue, nausea, headache, and anemia. Three patients discontinued the treatment due to an adverse event. Conclusion: These findings suggest that 12-week SOF-based regimen plus RBV or DCV or SIM is an efficacious and well-tolerated treatment in CHC patients with fibrosis stage F3–F4. Patients, who display risk factors for cirrhosis, should be referred to an experienced vir