从某核衣壳抑制剂临床试验结果看慢性乙肝抗病毒治疗评价指标选择的重要性  

The importance of selection of evaluation indicators for antiviral therapy of chronic hepatitis B based on the clinical trial results of a CpAM

作　　者：李桂馨 刘慧[2] 姜倩倩 陈红松[1] 鲁凤民 LI Gui-xin;LIU Hui;JIANG Qian-qian(Peking University People′s Hospital, Peking University Hepatology Institute, Beijing 100044, China)

机构地区：[1]北京大学人民医院,北京大学肝病研究所,北京100044 [2]北京大学基础医学院病原生物学系暨北京大学感染病研究中心,北京100191

出　　处：《中国临床新医学》2021年第12期1163-1168,共6页CHINESE JOURNAL OF NEW CLINICAL MEDICINE

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”计划项目(编号:2017ZX10302201);国家自然科学基金资助项目(编号:81672013)。

摘　　要：乙型肝炎病毒(HBV)感染仍是我国慢性肝病的主要病因之一。由于目前临床应用的抗病毒药物存在一定的局限性,靶向病毒复制过程及调节机体免疫的抗病毒新药的研发如火如荼。作为直接抗病毒药物,核心蛋白变构调节剂(CpAMs)由于能通过靶向HBV生命周期的多个环节发挥抗病毒作用,被认为是一类有潜力的在研抗乙肝病毒新药。但由于某项在研药物临床试验阶段因停药评价指标选择的问题,以致部分参与临床研究的患者在停药后出现病毒学反弹,甚至疾病复发。该文以CpAMs为例,对其临床试验结果进行解读,并提出在不同机制的抗病毒药物治疗下,安全停药指标还需谨慎全面地进一步总结。Hepatitis B virus(HBV)infection is still the leading cause of chronic liver disease in China.Due to the limitations of currently used antiviral drugs in clinic,new researches targeting different layers of HBV life cycle and host immunomodulation have attracted wide attention.Direct antiviral drugs,named core protein allosteric modulators(CpAMs),is considered as a class of potential new drugs that are being studied for the treatment of hepatitis B due to their multiple impacts on HBV life cycle.However,due to the problem of choosing the evaluation indicators for safe drug withdrawal in the clinical trial phase of a drug that is being studied,viral rebound and even disease recurrence is observed in a part of the patients involved in the clinical trials after secession of treatment.In this paper,CpAMs are taken as an example to interpret the clinical trial results of CpAMs,and it is suggested that safe drug withdrawal indicators should be further carefully and comprehensively summarized under different antiviral therapy mechanisms.

关 键 词：乙型肝炎病毒 慢性乙型肝炎 核心蛋白变构调节剂 

分 类 号：R512.6[医药卫生—内科学]