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World J Hepatol. May 18, 2015; 7(8): 1125-1132
Published online May 18, 2015. doi: 10.4254/wjh.v7.i8.1125
Natural interferon-beta treatment for patients with chronic hepatitis C in Japan
Reina Sasaki, Tatsuo Kanda, Shingo Nakamoto, Yuki Haga, Masato Nakamura, Shin Yasui, Xia Jiang, Shuang Wu, Makoto Arai, Osamu Yokosuka
Reina Sasaki, Tatsuo Kanda, Shingo Nakamoto, Yuki Haga, Masato Nakamura, Shin Yasui, Xia Jiang, Shuang Wu, Makoto Arai, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
Author contributions: Sasaki R, Kanda T, Nakamoto S, Haga Y, Nakamura M, Yasui S, Jiang X, Wu S, Arai M and Yokosuka O contributed to this paper.
Conflict-of-interest: Tatsuo Kanda reports receiving lecture fees from Chugai Pharmaceutical, MSD, Tanabe-Mitsubishi, Ajinomoto, Bristol-Myers Squibb, Daiichi-Sankyo, Janssen Pharmaceutical and GlaxoSmithKline; Makoto Arai reports receiving lecture fees from Chugai Pharmaceutical, Eisai, AstraZeneca, Daiichi Sankyo and Tsumura; Osamu Yokosuka reports receiving grant support from Chugai Pharmaceutical, Bayer, MSD, Daiichi-Sankyo, Tanabe-Mitsubishi, Bristol-Myers Squibb, Gilead Sciences and Taiho Pharmaceutical.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Tatsuo Kanda, MD, PhD, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. kandat-cib@umin.ac.jp
Telephone: +81-43-2262086 Fax: +81-43-2262088
Received: August 20, 2014
Peer-review started: August 22, 2014
First decision: December 17, 2014
Revised: January 15, 2015
Accepted: January 30, 2015
Article in press: February 2, 2015
Published online: May 18, 2015
Processing time: 271 Days and 21.8 Hours
Abstract

Chronic hepatitis C virus (HCV) infection can cause liver cirrhosis and hepatocellular carcinoma (HCC). Several studies have demonstrated that the eradication of HCV reduces the occurrence of HCC. In Japan, as many people live to an advanced age, HCV-infected patients are also getting older, and the age at HCC diagnosis has also increased. Although older HCV-infected patients have a risk of developing HCC, the treatment response to peginterferon-alpha plus ribavirin therapy is relatively poor in these patients because of drop-out or discontinuation of this treatment due to adverse events. It is established that the mechanism of action between interferon-alpha and interferon-beta is slightly different. Short-term natural interferon-beta monotherapy is effective for patients with acute hepatitis C and patients infected with HCV genotype 2 and low viral loads. Natural interferon-beta plus ribavirin for 48 wk or for 24 wk are also effective for some patients with HCV genotype 1 or HCV genotype 2. Natural interferon-beta plus ribavirin has been used for certain “difficult-to-treat” HCV-infected patients. In the era of direct-acting anti-virals, natural interferon-beta plus ribavirin may be one of the therapeutic options for special groups of HCV-infected patients. In the near future, signal transduction pathways of interferon-beta will inform further directions.

Keywords: Hepatocellular carcinoma, Hepatitis C virus, Interferon-beta, Interferon resistance, Ribavirin

Core tip: The use of natural interferon-beta plus ribavirin can eradicate hepatitis C virus (HCV) from non-responders to peginterferon-alpha plus ribavirin treatment. Some of these patients may have anti-interferon-alpha neutralizing antibodies. In Japan, natural interferon-beta plus ribavirin has been used for certain “difficult-to-treat” HCV-infected patients such as elderly patients, patients with mental disorders and patients with lower platelet counts, before the era of interferon-free regimens. To eradicate hepatocellular carcinoma and end-stage liver diseases associated with HCV, the use of natural interferon-beta with or without ribavirin should be one of the useful treatment options for HCV-infected patients.