Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 18, 2015; 7(26): 2681-2687
Published online Nov 18, 2015. doi: 10.4254/wjh.v7.i26.2681
Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C
Hirayuki Enomoto, Shuhei Nishiguchi
Hirayuki Enomoto, Shuhei Nishiguchi, Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Author contributions: All authors participated in the studies; Enomoto H and Nishiguchi S wrote and edited the manuscript; Enomoto H and Nishiguchi S were involved in the manuscript revision and approved the final version of the manuscript.
Conflict-of-interest statement: None of the authors have conflicts of interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Hirayuki Enomoto, MD, PhD, Division of Hepatobiliary and Pancreatic Disease, Department of Internal Medicine, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan.
Telephone: +81-798-456472 Fax: +81-798-456474
Received: June 27, 2015
Peer-review started: June 30, 2015
First decision: August 16, 2015
Revised: October 15, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: November 18, 2015

Hepatitis C virus (HCV) infection is a major health concern worldwide. Interferon-α (IFN-α) 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-α treatment. In addition, among the host factors related to the response to IFN-α 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-α treatment for chronic HCV infection. In addition, our recent findings regarding the possible involvement of anti-IFN-α neutralizing antibodies in a non-response to pegylated-IFN-α treatment are also described.

Keywords: Anti-interferon-α neutralizing antibody, Interferon-α, Direct-acting antiviral, Interferon-free treatment, Chronic hepatitis C

Core tip: Interferon-α (IFN-α) therapy has been playing a central role in anti-hepatitis C virus (HCV) strategies, and several viral and host factors related to the treatment efficacy have been identified. After the development of pegylated-IFN-α (Peg-IFN-α), the clinical impact of anti-IFN-α neutralizing antibodies in the treatment for HCV infection has not been sufficiently addressed. We recently found that anti-IFN-α neutralizing antibodies were associated with a non-response to Peg-IFN-α treatment. Our findings provide important information for the treatment of chronic hepatitis C in the clinical setting.