Host Genetics and Responses to Antiviral Therapy in Chronic Hepatitis C

Abstract

Genome-wide association studies (GWAS) have revealed recently that certain interleukin-28B (IL28B) polymorphisms are strongly associated with responses to pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy in patients chronically infected with hepatitis C virus (HCV) genotype 1. Subsequent reports revealed that these IL28B polymorphisms also affect treatment efficacy in chronic infection with other HCV genotypes. Therapy of chronic hepatitis C (CHC) recently has entered a new era with the availability of direct-acting antiviral agents (DAAs). These include non-structural 3/4A protease inhibitors which have shown promise in combination with PEG-IFN/RBV in several clinical trials, as well as in clinical practice. IFN-free therapy is expected to be useful especially for IFN-resistant patients and may become the standard of care in the future. Several clinical trials have revealed an association between IL28B genotype and treatment efficacy in triple therapy and in some interferon-free regimens. Recently, it was shown that a polymorphism of IFN-lambda 4 (IFNL4) is in high linkage disequilibrium with that of near IL28B and more strongly associated with spontaneous or treatment-induced HCV clearance than the IL28B polymorphisms, especially in individuals of African ancestry. This finding provides new insights into the genetic regulation of HCV clearance and its clinical management. IL28B genotyping will be useful for personalized treatment of CHC in the forthcoming era of DAAs.