Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C

Hepatitis C virus (HCV) infection is a major health concern worldwide. Interferon-alpha (IFN-alpha) therapy has been the main antiviral treatment for more than 20 years. Because of its established antitumor effects, IFN-based treatments for chronic HCV infection still have a clinical impact, particularly for patients with high risk conditions of developing hepatocellular carcinoma, such as older age and advanced liver fibrosis. As a result of exhaustive research, several viral factors, including NS5A amino acid mutations such as the IFN sensitivity-determining region and the IFN/ribavirin resistance-determining region, and mutations of amino acids in the core protein region (core 70 and 91) were shown to be associated with the response to IFN-alpha treatment. In addition, among the host factors related to the response to IFN-alpha treatment, polymorphisms of the interleukin-28B gene were identified to be the most important factor. In this article, we review the factors associated with the efficacy of IFN-alpha treatment for chronic HCV infection. In addition, our recent findings regarding the possible involvement of anti-IFN-alpha neutralizing antibodies in a non-response to pegylated-IFN-alpha treatment are also described.