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Review
. 2024 Jan 19;53(1):64-72.
doi: 10.3724/zdxbyxb-2023-0481.

Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma

[Article in English, Chinese]
Lingdong Xu  1   2 , Yifan Xu  3 , Fei Zhang  3   4 , Pinglong Xu  5   6   7   8 , Lie Wang  9   10
Affiliations
Review

Immunological pathways in viral hepatitis-induced hepato-cellular carcinoma

[Article in English, Chinese]
Lingdong Xu et al. Zhejiang Da Xue Xue Bao Yi Xue Ban. .

Abstract
in English, Chinese

Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.

肝炎病毒感染是肝细胞癌的主要致病因素之一。甲型肝炎病毒（HAV）通常引起急性感染，临床病理长期追踪结果显示HAV感染与肝细胞癌发生有一定联系。乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）的慢性感染可导致长期肝脏炎症和肝硬化，影响多条细胞凋亡和增殖相关信号通路，是病毒感染导致肝细胞癌的最常见诱因。HBV X蛋白（HBx）基因突变与肝细胞癌发病率密切相关，HCV核心蛋白的表达可导致肝细胞脂质积累，促进肿瘤发生。临床丁型肝炎病毒（HDV）感染常伴随HBV的共感染，从而增加慢性肝炎风险。戊型肝炎病毒（HEV）感染通常呈急性，近年HEV在器官移植和免疫缺陷患者中慢性感染增多。HEV慢性感染易导致肝硬化而增加肝细胞癌风险。本文概述了近年来肝炎病毒感染导致肝脏免疫应答异常和肝细胞癌发生的研究进展，以期有助于寻找病毒感染的早期检测、有效干预和疫苗接种的措施。.

Keywords: Chronic infection; Hepatitis virus; Hepatocellular carcinoma; Liver cirrhosis; Review; Viral hepatitis.

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Conflict of interest statement

所有作者均声明不存在利益冲突

The authors declare that there is no conflict of interests

Figures

图1
图1. HBV X蛋白诱导肝细胞癌发生的机制及靶点示意图
图2
图2. HCV诱导肝细胞癌发生的机制及靶点示意图
See this image and copyright information in PMC

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