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Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus

Challenge to overcome: Nonstructural protein 5A-P32 deletion in direct-acting antiviral-based therapy for hepatitis C virus

作     者:Ken Sato Toshio Uraoka 

作者机构:Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2018年第24卷第38期

页      面:4304-4310页

核心收录:

学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

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

摘      要:Interferon(IFN)-based therapy for hepatitis C virus(HCV) infection has recently been replaced by IFNfree direct-acting antiviral(DAA)-based therapy, which has been established as a 1^(st) line therapy with high efficacy and tolerability due to its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.

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