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丙型肝炎病毒NS3基因区域与直接作用抗病毒药物耐药性相关的主要突变:一项系统综述

Major mutations in the NS3 gene region of hepatitis C virus related to the resistance to direct acting antiviral drugs: a systematic review.

作者信息

Mundim Ana Elisa de Figueiredo Miranda, de Castro Fernanda de Oliveira Feitosa de, Albuquerque Marina Brandão Braz, Vilanova-Costa Cesar Augusto Sam Tiago, Pfrimer Irmtraut Araci Hoffmann, Silva Antonio Márcio Teodoro Cordeiro

机构信息

Programa de Pós-Graduação em Ciências Ambientais e Saúde, Pontifícia Universidade Católica de Goiás, Avenida Universitária 1.440, Setor Universitário, Campus 1, Área 4, Goiânia, GO CEP: 74605-010 Brazil.

Laboratório de Biologia Tumoral e Oncogenética, Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás, Goiânia, GO Brazil.

出版信息

Virusdisease. 2020 Sep;31(3):220-228. doi: 10.1007/s13337-020-00616-9. Epub 2020 Aug 4.

DOI:10.1007/s13337-020-00616-9
PMID:32904849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7459071/
Abstract

Hepatitis C virus (HCV) remains a global public health problem with high prevalence rates and chronicity of infection. Present work aimed to describe the main mutations in the NS3 region of the HCV genome related to the resistance of patients to the currently available direct-acting antivirals (DAAs). To guide the study description, the preferred items in the PRISMA protocol for systematic review were used. The data collected were HCV genotypes and subtypes and mutations in HCV NS3, general and stratified by continent. The 10 papers selected for this systematic review reported studies in seven countries, on three continents, and generated data of 2937 patients. The most frequent HCV subtype was 1a. Prevalence of genotypes suggested that there were few demographic regions reached by the studies, since there were regional variations in the type of genotypes reported in the available bibliographies. Of the total study population, 35.3% (n = 1037) had mutations in the NS3 gene region of HCV, suggesting a high rate of resistance to DAAs and a low sustained virologic response among those who used some therapeutic option. Ten major mutations were identified: Q80K, V170I, S122G, V36L, T54S, D168Q, A156S, Q80G, S122R, and V55A. The Q80K mutation was the highlight of the study, appearing not only with greater representativity (61.6%) but also as the only one described in the three continents analyzed. This systematic review reinforces the need to carry out more studies of detection of these mutations to fill in all information gaps that might help in optimization of treatment.

摘要

丙型肝炎病毒(HCV)仍然是一个全球性的公共卫生问题,感染率高且具有慢性化特点。目前的工作旨在描述HCV基因组NS3区域中与患者对当前可用直接抗病毒药物(DAA)耐药性相关的主要突变。为指导研究描述,采用了PRISMA系统评价方案中的首选条目。收集的数据包括HCV基因型和亚型以及HCV NS3中的突变,按大陆进行总体和分层分析。为该系统评价选定的10篇论文报告了在三大洲7个国家开展的研究,并生成了2937例患者的数据。最常见的HCV亚型是1a。基因型的流行情况表明,这些研究覆盖的人口统计学区域较少,因为现有文献中报告的基因型类型存在区域差异。在全部研究人群中,35.3%(n = 1037)的患者在HCV的NS3基因区域存在突变,这表明对DAA的耐药率较高,且在使用某些治疗方案的患者中持续病毒学应答率较低。确定了10个主要突变:Q80K、V170I、S122G、V36L、T54S、D168Q、A156S、Q80G、S122R和V55A。Q80K突变是该研究的重点,不仅出现频率更高(61.6%),而且是在分析的三大洲中唯一均有描述的突变。该系统评价强调需要开展更多检测这些突变的研究,以填补所有可能有助于优化治疗的信息空白。

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本文引用的文献

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Introduction to hepatitis C virus infection: Overview and history of hepatitis C virus therapies.丙型肝炎病毒感染简介:丙型肝炎病毒治疗概述及历史
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Evolution of multi-drug resistant HCV clones from pre-existing resistant-associated variants during direct-acting antiviral therapy determined by third-generation sequencing.第三代测序技术确定直接作用抗病毒治疗期间源于预先存在的耐药相关变异的多药耐药 HCV 克隆的进化。
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6
Identification of drug resistance and immune-driven variations in hepatitis C virus (HCV) NS3/4A, NS5A and NS5B regions reveals a new approach toward personalized medicine.丙型肝炎病毒(HCV)NS3/4A、NS5A和NS5B区域耐药性及免疫驱动变异的鉴定揭示了个性化医疗的新方法。
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State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization.抗击丙型肝炎病毒的现状、未解决的问题及未来研究方向:筛查、耐药性诊断和免疫的前景
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Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database.欧洲丙型肝炎病毒数据库中丙型肝炎病毒序列的多态性和耐药性突变
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NS3 Resistance-Associated Variants (RAVs) in Patients Infected with HCV Genotype 1a in Spain.西班牙丙型肝炎病毒1a基因型感染患者中的NS3耐药相关变异(RAV)
PLoS One. 2016 Sep 29;11(9):e0163197. doi: 10.1371/journal.pone.0163197. eCollection 2016.
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Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes.丙型肝炎病毒感染的全球流行病学:丙型肝炎病毒基因型分布与传播的最新情况
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