首都医科大学学报 ›› 2012, Vol. 33 ›› Issue (4): 530-533.doi: 10.3969/j.issn.1006-7795.2012.04.023

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慢性丙型肝炎直接抗病毒药物耐药研究进展

成军   

  1. 首都医科大学附属北京地坛医院, 北京 100015
  • 收稿日期:2012-05-30 修回日期:1900-01-01 出版日期:2012-08-21 发布日期:2012-08-21

Progress in studies on resistance to direct-acting antiviral agents in patients with chronic hepatitis C virus infection

CHENG Jun   

  1. Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
  • Received:2012-05-30 Revised:1900-01-01 Online:2012-08-21 Published:2012-08-21

摘要: 丙型肝炎病毒感染是导致肝硬化、肝细胞癌以及肝衰竭的主要原因之一。应用目前的标准治疗仅有约一半的患者可以清除病毒。现有多种直接抗病毒药物正在进行Ⅰ、Ⅱ、Ⅲ期临床试验,其作用靶点包括NS3蛋白酶、NS5A蛋白、NS5B RNA依赖的RNA聚合酶,它们通过与宿主细胞蛋白相互作用起到抑制丙型肝炎病毒(hepatitis C virus,HCV)复制的作用。由于HCV具有高度异质性且复制快速,单一应用直接抗病毒药物极易发生耐药。本文就直接抗病毒药物研发现状、耐药特征以及影响因素做一介绍。

关键词: 丙型肝炎病毒, 直接抗病毒药物, 耐药

Abstract: Hepatitis C virus infection is one of the leading causes of cirrhosis, hepatocellular carcinoma and liver failure. The current standard of care, a combination of Peg-IFN and ribavirin, eradicates the virus in only about 50% of patients. Direct-acting antiviral agents(DAAs) are in phase Ⅰ, Ⅱ and Ⅲ trials, which target the nonstructural 3 protease, the NS5A protein, the RNA-dependent RNA-polymerase NS5B. They directly inhibit HCV replication through interaction with host cell protein. Because of the high genetic heterogeneity of HCV and its rapid replication, monotherapy with DAAs possess a high risk for selection of resistant variants. This article reviews the progress in the research, resistance profiles and parameters of DAAs.

Key words: hepatitis C virus, direct-acting antiviral, resistance

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