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HCV 基因型对治疗方案和耐药性的影响:一个时间点的快照。

Impact of HCV genotype on treatment regimens and drug resistance: a snapshot in time.

机构信息

KU Leuven - University of Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, Leuven, Belgium.

Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy.

出版信息

Rev Med Virol. 2016 Nov;26(6):408-434. doi: 10.1002/rmv.1895. Epub 2016 Jul 12.

Abstract

The introduction of highly potent direct-acting antivirals (DAAs) has revolutionized hepatitis C virus treatment. Nevertheless, viral eradication worldwide remains a challenge also in the era of DAA treatment, because of the high associated costs, high numbers of undiagnosed patients, high re-infection rates in some risk groups and suboptimal drug efficacies associated with host and viral factors as well as advanced stages of liver disease. A correct determination of the HCV genotype allows administration of the most appropriate antiviral regimen. Additionally, HCV genetic sequencing improves our understanding of resistance-associated variants, either naturally occurring before treatment, acquired by transmission at HCV infection, or emerging after virological failure. Because treatment response rates, and the prevalence and development of drug resistance variants differ for each DAA regimen and HCV genotype, this review summarizes treatment opportunities per HCV genotype, and focuses on viral genetic sequencing to guide clinical decision making. Although approval of the first pan-genotypic DAA-only regimen is expected soon, HCV genetic sequencing will remain important because when DAA therapies fail, genotyping and resistance testing to select a new active DAA combination will be essential. Copyright © 2016 John Wiley & Sons, Ltd.

摘要

高效直接作用抗病毒药物(DAAs)的引入彻底改变了丙型肝炎病毒的治疗方法。然而,由于相关成本高、未确诊患者数量多、某些高危人群的再感染率高以及与宿主和病毒因素相关的药物疗效不佳以及肝病晚期等原因,在 DAA 治疗时代,全球范围内仍难以实现病毒清除。正确确定 HCV 基因型可使患者接受最适当的抗病毒治疗方案。此外,HCV 基因测序可提高我们对耐药相关变异体的认识,这些变异体可在治疗前、HCV 感染传播期间获得或在病毒学失败后出现。由于每种 DAA 方案和 HCV 基因型的治疗反应率、耐药变异体的流行率和发展情况不同,因此本综述按 HCV 基因型总结了治疗机会,并重点介绍了病毒基因测序以指导临床决策。虽然预计很快将批准首个泛基因型 DAA 单药治疗方案,但 HCV 基因测序仍将很重要,因为当 DAA 治疗失败时,基因分型和耐药性检测以选择新的有效 DAA 联合治疗方案将是必不可少的。版权所有©2016 年 John Wiley & Sons, Ltd.

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