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乙肝病毒诱导的致癌作用:机制、与病毒抑制的相关性及治疗意义

HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.

作者信息

Tu Thomas, McQuaid Thomas J, Jacobson Ira M

机构信息

Storr Liver Centre, Westmead Clinical School, Centre for Infectious Diseases and Microbiology and Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia.

Gilead Sciences Inc., Provincetown, Massachusetts, USA.

出版信息

Liver Int. 2025 Jan;45(1):e16202. doi: 10.1111/liv.16202.

Abstract

BACKGROUND

Chronic hepatitis B virus (HBV) infection is a common but underdiagnosed and undertreated health condition and is the leading cause of hepatocellular carcinoma (HCC) worldwide. HBV (rated a Grade 1 carcinogen by the International Agency for Research on Cancer) drives the transformation of hepatocytes in multiple ways by inducing viral DNA integrations, genetic dysregulation, chromosomal translocations, chronic inflammation, and oncogenic pathways facilitated by some HBV proteins. Importantly, these mechanisms are active throughout all phases of HBV infection. Nevertheless, most clinical guidelines for antiviral therapy recommend treatment based on a complex combination of HBV DNA levels, transaminasemia, liver histology, and demographic factors, rather than prompt treatment for all people with infection.

AIMS

To determine if current frameworks for antiviral treatment address the impacts of chronic HBV infection particularly preventing cancer development.

MATERIALS AND METHODS

We reviewed the recent data demonstrating pro-oncogenic factors acting throughout a chronic HBV infection can be inhibited by antiviral therapy.

RESULTS

We extensively reviewed Hepatitis B virology data and correlating clinical outcome data. From thi, we suggest that new findings support simplifying and expanding treatment initiation to reduce the incidence ofnew infections, progressive liver disease, and risk of hepatocellular carcinoma. We also consider lessons learned from other blood-borne pathogens, including the benefits of antiviral treatment in preventing transmission, reducing stigma, and reframing treatment as cancer prevention.

CONCLUSION

Incorporating these practice changes into treatment is likely to reduce the overall burden of chronic HBV infections and HCC. Through this, we may better achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat and minimise its impact on people's lives.

摘要

背景

慢性乙型肝炎病毒(HBV)感染是一种常见但诊断不足和治疗不足的健康状况,是全球肝细胞癌(HCC)的主要原因。HBV(被国际癌症研究机构评为1级致癌物)通过诱导病毒DNA整合、基因失调、染色体易位、慢性炎症以及一些HBV蛋白促进的致癌途径,以多种方式驱动肝细胞的转化。重要的是,这些机制在HBV感染的所有阶段都很活跃。然而,大多数抗病毒治疗临床指南建议根据HBV DNA水平、转氨酶血症、肝脏组织学和人口统计学因素的复杂组合进行治疗,而不是对所有感染者立即进行治疗。

目的

确定当前的抗病毒治疗框架是否解决了慢性HBV感染的影响,特别是预防癌症的发生。

材料和方法

我们回顾了最近的数据,这些数据表明抗病毒治疗可以抑制慢性HBV感染全过程中的促癌因素。

结果

我们广泛回顾了乙型肝炎病毒学数据和相关的临床结果数据。由此,我们建议新的研究结果支持简化和扩大治疗起始范围,以降低新感染、进行性肝病和肝细胞癌风险的发生率。我们还考虑了从其他血源性病原体中吸取的经验教训,包括抗病毒治疗在预防传播、减少耻辱感以及将治疗重新定义为癌症预防方面的益处。

结论

将这些实践改变纳入治疗可能会减轻慢性HBV感染和HCC的总体负担。通过这样做,我们可能更好地实现世界卫生组织消除病毒性肝炎作为公共卫生威胁的目标,并最大限度地减少其对人们生活的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6097/11669079/8d8707869544/LIV-45-0-g001.jpg

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