Oncogenesis and Molecular Virology Unit, Institut Pasteur, Inserm U579, 28 rue du Dr Roux, Paris cedex 15, France.
J Hepatol. 2010 Apr;52(4):594-604. doi: 10.1016/j.jhep.2009.10.033. Epub 2010 Jan 7.
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.
乙型肝炎病毒（HBV）是一种小型包膜 DNA 病毒，主要感染肝细胞并导致急性和持续性肝脏疾病。流行病学研究提供了确凿的证据表明，慢性 HBV 感染在肝细胞癌的发展中起因果作用，但病毒诱导肿瘤发生的分子机制仍存在很大争议。在 HBV 基因组中没有编码显性癌基因的情况下，已经提出了间接作用，包括 HBV DNA 整合对细胞癌相关基因的插入激活、病毒整合或调节蛋白 HBx 引起的遗传不稳定性以及病毒蛋白在增强免疫介导的肝脏疾病方面的长期作用。最近的遗传研究表明，HBV 相关肿瘤表现出独特的特征，染色体改变率高，β-连环蛋白突变频率低。这篇综述将讨论慢性 HBV 感染作为原发性肝癌的因果危险因素的证据。它还将讨论由于长期 HBV 感染而对肿瘤发生过程至关重要的分子机制。
