Mechanisms of HBV-related hepatocarcinogenesis

被引:329
作者
Neuveut, Christine [1 ]
Wei, Yu [1 ]
Buendia, Marie Annick [1 ]
机构
[1] Inst Pasteur, INSERM, U579, Oncogenesis & Mol Virol Unit, F-75724 Paris 15, France
关键词
Virus; Cancer; Hepatitis; Hepatocellular carcinoma; Oncogene; Tumour suppressor; HEPATITIS-B-VIRUS; HUMAN HEPATOCELLULAR-CARCINOMA; CORE PROMOTER MUTATIONS; BETA-CATENIN MUTATIONS; CIRCULAR VIRAL-DNA; X-PROTEIN; E-ANTIGEN; GENE-EXPRESSION; IN-VIVO; LIVER-CANCER;
D O I
10.1016/j.jhep.2009.10.033
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechanisms underlying virally-induced tumourigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including insertional activation of cellular cancer-related genes by HBV DNA integration, induction of genetic instability by viral integration or by the regulatory protein HBx, and long-term effects of viral proteins in enhancing immune-mediated liver disease. Recent genetic studies indicate that HBV-related tumours display a distinctive profile with a high rate of chromosomal alterations and low frequency of beta-catenin mutations. This review will discuss the evidence implicating chronic HBV infection as a causal risk factor of primary liver cancer. It will also discuss the molecular mechanisms that are critical for the tumourigenic process due to long lasting infection with HBV. (c) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:594 / 604
页数:11
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