乙型肝炎功能性治愈新药: 聚焦反义寡核苷酸和小干扰RNA

梁携儿, 刘智泓, 侯金林

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临床肝胆病杂志 ›› 2025, Vol. 41 ›› Issue (1) : 7-14. DOI: 10.12449/JCH250102
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乙型肝炎功能性治愈新药: 聚焦反义寡核苷酸和小干扰RNA

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New drugs for the functional cure of hepatitis B: Focusing on antisense oligonucleotides and small interfering RNAs

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摘要

在乙型肝炎治疗领域,现有的核苷(酸)类似物以及聚乙二醇干扰素在功能性治愈方面的疗效较为有限。最近,反义寡核苷酸与小干扰RNA等小核酸药物以全新的作用机制和令人瞩目的早期临床研究疗效,为乙型肝炎的功能性治愈带来了前所未有的突破性进展。反义寡核苷酸和小干扰RNA等小核酸药物可降低HBsAg水平甚至HBsAg转阴。随着HBsAg的减少,可能部分恢复机体的乙型肝炎特异性免疫功能,并可能将单纯的HBsAg清除进一步转化为减少乙型肝炎相关肝脏事件等具有临床价值的硬终点。紧密结合新药背景下HBsAg的动态变化轨迹,进一步优化联合治疗的策略与方案,有望将乙型肝炎功能性治愈转化为提升患者生存率及显著改善其生活质量的最终目标。

Abstract

Existing nucleos(t)ide analogues and pegylated interferon exhibit limited efficacy in the functional cure of hepatitis B. Recently, small nucleic acid drugs, such as antisense oligonucleotides and small interfering RNAs, have brought unprecedented breakthroughs in the functional cure of hepatitis B with their brand-new mechanisms of action and remarkable efficacy in early clinical studies. Small nucleic acid drugs, such as antisense oligonucleotides and small interfering RNAs, can reduce the level of HBsAg and strive to achieve HBsAg seroclearance. The reduction in HBsAg may restore the hepatitis B-specific immune function of the body to some extent and may further transform the simple clearance of HBsAg into hard endpoints with clinical value, such as reducing hepatitis B-related liver events. By meticulously analyzing the dynamic trajectory of HBsAg alterations within the context of new drug applications and further optimizing combined treatment strategies and regimens, it is expected to transform the functional cure of hepatitis B into the ultimate goal of improving survival rates and quality of life.

关键词

乙型肝炎 / 寡核苷酸类, 反义 / RNA, 小分子干扰 / 乙型肝炎表面抗原 / 功能性治愈

Key words

Hepatitis B / Oligonucleotides, Antisense / RNA, Small Interfering / Hepatitis B Surface Antigens / Functional Cure

引用本文

导出引用
梁携儿 , 刘智泓 , 侯金林. 乙型肝炎功能性治愈新药: 聚焦反义寡核苷酸和小干扰RNA. 临床肝胆病杂志. 2025, 41(1): 7-14 https://doi.org/10.12449/JCH250102
Xieer LIANG, Zhihong LIU, Jinlin HOU. New drugs for the functional cure of hepatitis B: Focusing on antisense oligonucleotides and small interfering RNAs[J]. Journal of Clinical Hepatol. 2025, 41(1): 7-14 https://doi.org/10.12449/JCH250102

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作者贡献声明

南方医科大学南方医院感染内科为本研究第一完成单位。梁携儿负责研究设计,文章撰写;梁携儿、刘智泓参与研究数据/信息的收集与解读分析;侯金林、梁携儿负责文章提纲与全文审核。

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