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衣壳组装调节剂联合核苷(酸)类似物治疗慢性乙型肝炎临床试验中亟待解决的科学问题

鲁凤民 黄鸿鑫 毛天皓 陈香梅 庄辉

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衣壳组装调节剂联合核苷(酸)类似物治疗慢性乙型肝炎临床试验中亟待解决的科学问题

DOI: 10.3969/j.issn.1001-5256.2022.08.001
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:鲁凤民、庄辉拟定写作思路并最终定稿;陈香梅指导文章撰写并修改文章关键内容;黄鸿鑫和毛天皓负责文献检索并参与起草文稿。
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    通信作者:

    鲁凤民, lu.fengmin@hsc.pku.edu.cn

    庄辉, zhuangbmu@126.com

Urgent scientific issues to be solved in clinical trials of capsid assembly modulator combined with nucleos(t)ide analogues for the treatment of chronic hepatitis B

More Information
  • 摘要: 慢性HBV感染是病毒性肝炎、肝硬化和原发性肝癌的主要病因。目前临床应用的核苷(酸)类似物(NUC)和聚乙二醇干扰素α(PEG-IFNα)均无法直接靶向共价闭合环状DNA,难以实现慢性乙型肝炎患者(CHB)的临床治愈。因此,亟需研发靶向HBV复制周期各阶段的直接抗病毒药物。衣壳组装调节剂(CpAM)通过不同机制靶向病毒衣壳的组装,进而发挥直接抗病毒作用,其与NUC联用本应发挥良好的协同抗病毒作用,但现有临床试验结果均表明,接受有限疗程CpAM与NUC联合抗病毒治疗的慢性乙型肝炎患者均发生停药后病毒学反弹。本文根据两类药物的作用机制,对上述临床试验结果进行了合理解释,并提出在未来以安全停药为观察终点的临床试验中,可能需要更长时间的CpAM与NUC联合抗病毒治疗,以耗竭或沉默共价闭合环状DNA池,从而提高CHB患者安全停药的可能性。此外,多靶点的联合抗病毒治疗策略仍需进一步研究。

     

  • 图  1  影响CpAM联合NUC对抑制HBV DNA复制发挥叠加作用的可能机制及启示

    Figure  1.  Possible mechanisms that affect the combined use of CpAM and NUC to exert the superimposed antiviral effects on inhibition of HBV DNA replication and their implications

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  • 收稿日期:  2022-04-20
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