干扰素和核苷(酸)类似物治疗对HBV cccDNA的影响与慢性乙型肝炎的功能性治愈

陈捷亮; 袁正宏

doi:10.3969/j.issn.1001-5256.2019.06.002

干扰素和核苷(酸)类似物治疗对HBV cccDNA的影响与慢性乙型肝炎的功能性治愈

DOI: 10.3969/j.issn.1001-5256.2019.06.002

基金项目:

国家自然科学基金(81772189)；国家科技重大专项(2018ZX10301208)；中国医学科学院科研基金(2018PT31044)；上海市教委科研创新计划(201701070007E00057)；

详细信息

中图分类号: R512.62
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出版历程
- 收稿日期: 2019-04-09
- 出版日期: 2019-06-20

Influence of interferon and nucleos (t) ide analogues on HBV cccDNA and functional cure of chronic hepatitis B

Research funding:

摘要

摘要: 目前临床治疗慢性乙型肝炎的药物主要包括干扰素和核苷(酸)类似物两大类,但均无法有效清除病毒和治愈乙型肝炎。HBV共价闭合环状DNA(cccDNA)作为HBV转录复制的模板,以微小染色体形式持续存在于细胞核内,被认为是HBV慢性感染和难以治愈的关键核心。鉴于cccDNA很难被彻底清除,近年来以cccDNA持续沉默为基础的慢性乙型肝炎功能性治愈已成为临床和基础研究的主要目标。从现有治疗手段对cccDNA的影响切入,介绍当前对cccDNA含量和活性受控因素的认知,探讨cccDNA池难以清除的关键特性环节,在此基础上展望功能性治愈慢性乙型肝炎目标下研究cccDNA的重点。
- 乙型肝炎病毒 /
- 抗病毒药 /
- 共价闭合环状DNA
Abstract: At present, interferon (IFN) and nucleos (t) ide analogues (NAs) remain the most important methods for the treatment of chronic hepatitis B in clinical practice, but neither of them can effectively eliminate the virus and cure hepatitis B. As the template for HBV transcription and replication, HBV covalently closed circular DNA (cccDNA) persistently exists in the nucleus in the form of minichromosome and is considered the most important reason for chronic and refractory HBV infection. Since it is hard to completely eliminate cccDNA, functional cure of chronic hepatitis B through sustained silencing of cccDNA has become a major goal of clinical and basic research in recent years. This article reviews the influence of current treatment methods on cccDNA, the factors regulating the amount and activity of cccDNA, and the key obstacles to eradication of cccDNA pool, with perspectives of cccDNA research towards a functional cure of chronic hepatitis B.
- hepatitis B virus /
- antiviral agents /
- covalently closed circular DNA

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