Factors determining effectiveness of interferons in managing hepatitis C: new targets and new approaches

Abstract

Factors determining effectiveness of interferons in managing hepatitis C: new targets and new approaches N Rajoriya1, Eleanor Barnes1,21Department of Pathogen Research, Peter Medawar Building, South Parks Road, Oxford, UK; 2Oxford National Institute of Health Research Biomedical Research Centre, Oxford, UKAbstract: The hepatitis C virus now infects 170 million people worldwide. The majority of infected people develop viral persistence that may lead to increasing liver fibrosis, liver cirrhosis, and hepatocellular cancer. Interferon therapy has been the mainstay of treatment for hepatitis C since the discovery of the virus in 1989. The introduction of a pegylated form of interferon that increases the half-life of interferon, and the concurrent use of ribavirin has ­significantly improved the likelihood of achieving long-term viral eradication. HCV genotype and viral load remain major determinants of response to interferons. However, very recently, host genetic polymorphisms linked to interferon-λ3 have also been shown to play a crucial role in clinical outcome. A significant body of evidence now exists showing that the hepatitis C virus has developed multiple strategies to subvert both the production and the antiviral effects of interferons. This review explores these strategies, the factors that determine the effectiveness of interferon therapy, and highlights novel interferons in development. Ultimately, given the significant side effect profile of interferon therapy, and the emergence of small molecules and therapeutic vaccines that may inhibit viral replication, the aim will be to achieve viral ­eradication without interferon treatment.Keywords: hepatitis C virus, interferon, ribavirin, novel interferons, interferon-λ, pharmacodynamics