Emerging therapies for hepatitis C

Abstract

The combination of pegylated interferon (PEG-IFN) and ribavirin (RBV), the current therapy for hepatitis C virus (HCV) infection, has saved the lives of many HCV-infected patients. Direct-acting antivirals (DAAs) target several sites of HCV nonstructural proteins, resulting in the cessation of viral replication. The first NS3/4A protease inhibitors consisted of boceprevir and telaprevir, which have shown superior efficacy against genotype 1 HCV infection when combined with PEG-IFN/RBV compared with the standard therapy in both treatment-naive and -experienced patients. Simeprevir, faldaprevir, and asunaprevir are second-wave, first-generation NS3/4A inhibitors that have already been or will soon be approved. Second-generation protease inhibitors are in clinical trials. Daclatasvir is the first approved DAA belonging to the class of NS5A replication complex inhibitors. The potency of daclatasvir is very high, and this drug is an important and essential component of combination regimens for all genotypes. Sofosbuvir, the first approved NS5B polymerase inhibitor, is characterized by high potency and genetic barriers to resistance. Sofosbuvir combined with RBV achieved an interferon-free regimen in genotype 2 or 3 patients with a reduced treatment duration. It can also be used in combination with PEG-IFN/RBV in genotype 1 patients for 12 weeks. DAAs have provided new hope for curing HCV infections with a short treatment duration and acceptable adverse events.