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The goal of antiviral therapy for patients with HCV is virologic cure. Eradication of HCV RNA, which remains undetectable long term off therapy, is referred to as a sustained virologic response and is now an increasingly achievable prospect thanks to the availability of direct-acting antivirals (DAAs). Several new classes of DAAs have been approved for the treatment of chronic HCV infection during the last 4 years, leading to dramatic shifts in the HCV landscape. This module focuses on evidence-based management approaches for patients with HCV infection, including treatment of patients with cirrhosis, strategies for drug resistance, and posttreatment management.