Minireviews
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8120-8127
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8120
Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b
Tatsuo Kanda, Kazushige Nirei, Naoki Matsumoto, Teruhisa Higuchi, Hitomi Nakamura, Hiroaki Yamagami, Shunichi Matsuoka, Mitsuhiko Moriyama
Tatsuo Kanda, Kazushige Nirei, Naoki Matsumoto, Teruhisa Higuchi, Hitomi Nakamura, Hiroaki Yamagami, Shunichi Matsuoka, Mitsuhiko Moriyama, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan
Author contributions: These authors contributed to all aspects of this paper.
Supported by AMED; and JSPS KAKENHI, No. 17K09404.
Conflict-of-interest statement: Kanda T received research grants from AbbVie, MSD, Chugai Pharma and Sysmex. These company played no role in this study. Other authors declare no conflict of interest related to this publication.
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, Associate Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan. kandat-cib@umin.ac.jp
Telephone: +81-3-39728111 Fax: +81-3-39568496
Received: October 13, 2017
Peer-review started: October 13, 2017
First decision: October 30, 2017
Revised: November 10, 2017
Accepted: October 28, 2017
Article in press: November 28, 2017
Published online: December 14, 2017
Processing time: 60 Days and 16.7 Hours
Abstract

The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

Keywords: Direct-acting antiviral agent; Genotype 1b; Hepatitis C virus; Resistance-associated substitutions

Core tip: In this minireview, we focused on the retreatment of patients with treatment failure of direct-acting antiviral agents against hepatitis C virus genotype 1b (HCV GT1b) infection. We summarized the retreatment regimens for patients with failure of peginterferon and ribavirin plus HCV NS3/4A inhibitors and for those with failure of HCV NS5A inhibitors. We also demonstrated the resistance-associated substitutions of HCV NS5B nucleos(t)ide inhibitors. Attention should be paid when selecting both the initial treatment and retreat regimens to completely eradicate HCV infection.