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尽早启动抗病毒治疗降低慢性HBV感染者肝细胞癌发生风险

周召 阿卜杜热西提·阿卜来提 顾智强 常靖 刘新 鲁凤民

引用本文:
Citation:

尽早启动抗病毒治疗降低慢性HBV感染者肝细胞癌发生风险

DOI: 10.3969/j.issn.1001-5256.2023.01.005
基金项目: 

国家自然科学基金面上项目 (82072280);

北京自然科学基金面上项目 (7212063)

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、周召、阿卜杜热西提·阿卜来提、顾智强、常靖负责撰写论文;鲁凤民、顾智强、刘新负责修改论文;鲁凤民负责拟定写作思路,指导撰写文章。
详细信息
    通信作者:

    鲁凤民,lu.fengmin@hsc.pku.edu.cn (ORCID: 0000-0002-1832-3209)

Early initiation of antiviral therapy reduces the risk of hepatocellular carcinoma in individuals with chronic hepatitis B virus infection

Research funding: 

General Project of National Natural Science Foundation of China (82072280);

General Project of Natural Science Foundation of Beijing (7212063)

More Information
  • 摘要: 慢性HBV感染是病毒性肝炎、肝硬化和肝细胞癌(HCC)的主要致病原因。从慢性HBV感染到HCC发生,多数患者会经过慢性肝炎-肝硬化-HCC等不同阶段。在这一漫长的过程中,HBV不断将自身DNA整合入宿主DNA,起到促癌的效果;而持续的肝脏炎症所致肝细胞的死亡与代偿性增殖更会带来突变的积累,并最终导致肝细胞的恶性转化。目前临床上广泛应用的抗HBV药物,即核苷(酸)类似物,通过抑制HBV复制来控制感染,可有效减缓疾病进程和终末期肝病发生,但由于目前抗HBV治疗启动较晚,治疗率较低,HBV相关HCC发生率仍呈上升趋势。如何改善现行的抗病毒治疗策略,以进一步降低包括HCC在内的HBV相关终末期肝病的发生风险,已成为临床关注的热点问题之一。因此,本文在回顾和总结既往支持扩大抗病毒治疗的研究和观点的基础上,建议应尽早启动抗病毒治疗,从而抑制病毒复制,减少整合事件发生,并最终降低慢性HBV感染者HCC发生风险。

     

  • 图  1  NUC类药物和PEG-IFNα抑制HCC发生

    注:HBV感染细胞后,HBV DNA可整合到宿主DNA上,若携带整合HBV DNA的肝细胞增殖速度远超正常肝细胞的自我更新速度,克隆性扩增细胞出现选择性优势。若增殖速度并不明显大于正常肝细胞的自我更新速度,则不会出现选择优势,难以形成大的克隆增生。NUC抑制HBV复制,新合成的rcDNA及dslDNA显著减少,间接减少了整合发生;PEG-IFNα则主要通过激活HBV特异性CD8+ T淋巴细胞的杀伤反应抑制有选择性优势的整合细胞,促进对克隆扩增的免疫清除。NUC及PEG-IFNα联用时,在阻止新整合事件的发生的同时,使已有克隆在数量和大小有所减少,HCC发生风险进一步下降。

    Figure  1.  Antiviral nucleos(t)ide analogs and PEG-IFNα inhibiting the occurrence of HCC

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  • 收稿日期:  2022-11-18
  • 出版日期:  2023-01-20
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