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Updated: May 6, 2026

Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Resistance to direct antiviral agents in patients with hepatitis C virus infection
Christoph Sarrazin1, Stefan Zeuzem
1J. W. Goethe-University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany. sarrazin@em.unifrankfurt.de
Abstract:
Chronic hepatitis C virus (HCV) infection is one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure that leads to transplantation. The current standard treatment, a combination of pegylated interferon alfa and ribavirin, eradicates the virus in only about 50% of patients. Directly acting antiviral (DAA) agents, which inhibit HCV replication, are in phase 1, 2, and 3 trials; these include reagents that target the nonstructural (NS)3 protease, the NS5A protein, the RNA-dependent RNA-polymerase NS5B, as well as compounds that directly inhibit HCV replication through interaction with host cell proteins. Because of the high genetic heterogeneity of HCV and its rapid replication, monotherapy with DAA agents poses a high risk for selection of resistant variants. We review the parameters that determine resistance, genotypic and phenotypic resistance profiles of DAA agents, and strategies to avoid the selection of resistant variants.
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