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
Early initiation of antiviral therapy reduces the risk of hepatocellular carcinoma in individuals with chronic hepatitis B virus infection
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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。
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关键词:
- 乙型肝炎病毒 /
- 癌, 肝细胞 /
- 核苷(酸)类似物 /
- 治疗学
Abstract: Chronic hepatitis B virus (HBV) infection is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). From chronic HBV infection to HCC, most patients go through the stages of chronic hepatitis, liver cirrhosis, and HCC. During this long process, the ongoing integration of HBV DNA into host DNA increases the risk of HCC, and the death and compensatory proliferation of hepatocytes caused by persistent liver inflammation may promote the accumulation of oncogenic mutations and finally lead to the malignant transformation of hepatocytes. Currently, nucleos(t)ide analogues are widely used anti-HBV drugs, which controls infection by inhibiting HBV replication and can thus effectively slow down disease progression and end-stage liver disease; however, anti-HBV therapy often starts late and has a relatively low treatment rate, and there is still a tendency of increase in the incidence rate of HBV-related HCC. Therefore, how to improve current antiviral strategies to further reduce the risk of HBV-related end-stage liver disease including HCC has become a hotspot in clinical practice. This article summarizes the previous studies supporting the expansion of antiviral therapy and suggests that antiviral therapy should be initiated as early as possible to inhibit viral replication and the sequential events of HBV DNA integration and ultimately reduce the risk of HCC in patients with chronic HBV infection.-
Key words:
- Hepatitis B virus /
- Carcinoma, Hepatocellular /
- Nucleos(t)ide Analogs /
- Therapeutics
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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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