Editorial
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2018; 24(38): 4304-4310
Published online Oct 14, 2018. doi: 10.3748/wjg.v24.i38.4304
Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus
Ken Sato, Toshio Uraoka
Ken Sato, Toshio Uraoka, Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Author contributions: Sato K reviewed the literature and wrote the first draft of the paper; Uraoka T approved the final version of the article.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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: Ken Sato, MD, PhD, Associate Professor, Doctor, Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. satoken@gunma-u.ac.jp
Telephone: +81-272-208127 Fax: +81-272-208127
Received: July 17, 2018
Peer-review started: July 17, 2018
First decision: July 25, 2018
Revised: August 2, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 14, 2018
Processing time: 86 Days and 23.1 Hours
Abstract

Interferon (IFN)-based therapy for hepatitis C virus (HCV) infection has recently been replaced by IFN-free direct-acting antiviral (DAA)-based therapy, which has been established as a 1st line therapy with high efficacy and tolerability due to its reasonable safety profile. Resistance-associated substitutions (RASs) have been a weakness of DAA-based therapy. For example, combination therapy with daclatasvir and asunaprevir (DCV/ASV) is less effective for HCV genotype 1-infected patients with Y93H as a nonstructural protein 5A RAS. However, the problem regarding RASs has been gradually overcome with the advent of recently developed DAAs, such as sofosbuvir-based regimens or combination therapy with glecaprevir and pibrentasvir. Despite the high efficiency of DAA-based therapy, some cases fail to achieve viral eradication. P32 deletion, an NS5A RAS, has been gradually noticed in patients with DCV/ASV failure. P32 deletion has been sporadically reported and the prevalence of this RAS has been considered to be low in patients with DCV/ASV failure. Thus, the picture of P32 deletion has not been fully evaluated. Importantly, currently-commercialized DAA-based combination therapy was not likely to be effective for patients with P32 deletion. Exploring and overcoming this RAS is essential for antiviral therapy for chronic hepatitis C.

Keywords: Chronic hepatitis C, Direct-acting antivirals, Resistant-associated substitution, P32 deletion, Nonstructural protein 5A

Core tip: P32 deletion, as a nonstructural protein 5A resistance-associated substitution (RAS), has been gradually noticed in patients who experience treatment failure associated with daclatasvir and asunaprevir as an antiviral therapy for chronic hepatitis C. Information regarding P32 deletion is very limited at the present. Although the prevalence of this RAS is assumed to be low, it was found to be a new threat to current direct-acting antiviral-based combination therapy. There is an urgent need for further basic and clinical studies on this RAS. Exploring and overcoming this RAS is essential for antiviral therapy for chronic hepatitis C.