摘要
乙型肝炎病毒(HBV)在世界范围内流行。每年60余万人死于HBV感染所致的肝硬化、肝功能衰竭和肝细胞癌,极大地威胁着人类的生命健康,是一项世界范围内的公共卫生问题。核苷(酸)类和干扰素类药物是现今临床上应用最广泛的两类抗病毒药物,但它们都不能直接靶向肝细胞核内的共价闭合环状DNA(cccDNA),致使慢性乙型肝炎(CHB)患者肝组织内的cccDNA无法彻底清除而久治不愈,且停药后易复发使得患者不得不接受长期甚至终生的抗病毒治疗。cccDNA定量是临床评价治疗效果和预测停药终点的重要指标,但因需要肝组织穿刺活检,具有一定的局限性。血清HBV RNA作为cccDNA的转录产物,是反映cccDNA活性的理想血清学替代指标。对于这一新兴的病毒学指标,本文从其来源和本质与反映cccDNA活性的能力进行梳理,并围绕血清HBV RNA解读核苷(酸)类药物(NAs)对HBV复制的影响,以及病毒颗粒中核酸类型的变化,总结近年来慢性乙肝防治指南及专家共识对HBV RNA作为检测新指标的采纳情况,探讨其在CHB抗病毒治疗和新药研发过程中的指导意义。
Hepatitis B virus(HBV) is prevalent worldwide. More than 600 000 people die from liver cirrhosis, liver failure and hepatocellular carcinoma caused by HBV infection annually, making it a serious threaten to human life and health. Nucleos(t)ide analogs and interferons are two main antiviral agents used in clinical practice, but neither of them directly target or eliminate intrahepatic covalently closed circular(cccDNA), which is exactly why chronic hepatitis B(CHB) is difficult to be cured and it also contributes to viral rebound after secession of antiviral therapy. Therefore, quantification of intrahepatic cccDNA is of great significance in evaluating efficacy and estimating the endpoint of antiviral treatment. However, several limitations prevent the liver biopsy from being a routine clinical practice. Serum HBV RNA has been suggested as one of the ideal surrogates of cccDNA activity. This article summarizes the features of serum HBV RNA and its potentials to reflect the activity of intrahepatic cccDNA. Also, we discuss some clinical practice guidelines on the management of HBV infection and expert consensuses that accept HBV RNA as biomarkers. And finally, we expect its future use as an indicator to evaluate the antiviral activity of new therapeutic compounds.
作者
刘明琛
杨兴雯
鲁凤民
LIU Ming-Chen;YANG Xing-Wen;LU Feng-Min(Department of Microbiology&Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China;Hepatology Institute,Peking University People’s Hospital,Beijing 100044,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第8期865-871,共7页
Chinese Journal of Biochemistry and Molecular Biology
基金
国家“艾滋病和病毒性肝炎等重大传染病防治”科技重大专项“十三五”计划(No.2017ZX10302201)
国家自然科学基金资助项目(No.81672013)资助。
