Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma.

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma.
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病毒性肝炎诱发肝癌的分子机制。

DOI:
10.3748/wjg.v26.i38.5759
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发表时间:
2020-10-14
影响因子:
4.3
通讯作者:
Patel TR
Patel TR
中科院分区:
医学2区
文献类型:
--
作者:
D'souza S;Lau KC;Coffin CS;Patel TR

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病毒性肝炎的慢性感染影响全球5亿人,并可导致肝硬化、癌症和肝功能衰竭。肝癌是癌症相关死亡的第三大原因,其中肝细胞癌(HCC)占所有原发性肝癌的90%。像HCC这样的实体瘤是复杂的,并且具有异质性肿瘤基因组谱,导致诊断和管理的复杂性。B型肝炎病毒(HBV)、丁型肝炎病毒(HDV)和丙型肝炎病毒(HCV)的慢性感染是HCC的最大病因危险因素。由于慢性病毒感染在HCC发展中的重要作用,研究HCC发病机制中的直接(病毒相关)和间接(免疫相关)机制非常重要。HBV、HCV和HDV驱动肝癌发生的常见机制包括持续性肝脏炎症伴抗病毒免疫应答受损、免疫和病毒蛋白介导的氧化应激以及病毒蛋白对细胞信号传导途径的失调。DNA整合促进基因组不稳定性是HBV感染的特征,而导致脂肪变性的代谢重编程是由HCV感染驱动的。本文综述了HBV、HCV和HDV的分子生物学,并重点介绍了HCC中病毒相关的致癌机制和常见的失调分子通路,以及目前和新出现的HCC治疗方法。
Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis, cancer, and liver failure. Liver cancer is the third leading cause of cancer-associated mortality, of which hepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management. Chronic infection with hepatitis B virus (HBV), hepatitis delta virus (HDV), and hepatitis C virus (HCV) are the greatest etiological risk factors for HCC. Due to the significant role of chronic viral infection in HCC development, it is important to investigate direct (viral associated) and indirect (immune-associated) mechanisms involved in the pathogenesis of HCC. Common mechanisms used by HBV, HCV, and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response, immune and viral protein-mediated oxidative stress, and deregulation of cellular signaling pathways by viral proteins. DNA integration to promote genome instability is a feature of HBV infection, and metabolic reprogramming leading to steatosis is driven by HCV infection. The current review aims to provide a brief overview of HBV, HCV and HDV molecular biology, and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC, and current as well as emerging treatments for HCC.
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