Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
Semin Liver Dis. 2021 May;41(2):142-149. doi: 10.1055/s-0041-1723033. Epub 2021 May 6.
Current treatments for hepatitis B virus (HBV) using nucleos(t)ide analogs cannot eliminate the risk of hepatocellular carcinoma (HCC) development. As HBV-associated HCC can develop even in the absence of liver cirrhosis, HBV is regarded to possess direct oncogenic potential. HBV regulatory protein X (HBx) has been identified as a primary mediator of HBV-mediated hepatocarcinogenesis. A fragment of the HBV genome that contains the coding region of HBx is commonly integrated into the host genome, resulting in the production of aberrant proteins and subsequent hepatocarcinogenesis. Besides, HBx interferes with the host DNA or deoxyribonucleic acid damage repair pathways, signal transduction, epigenetic regulation of gene expression, and cancer immunity, thereby promoting carcinogenesis in the noncirrhotic liver. However, numerous molecules and pathways have been implicated in the development of HBx-associated HCC, suggesting that the mechanisms underlying HBx-mediated hepatocarcinogenesis remain to be elucidated.
目前使用核苷（酸）类似物治疗乙型肝炎病毒 (HBV) 并不能消除肝细胞癌 (HCC) 发展的风险。由于 HBV 相关 HCC 甚至在没有肝硬化的情况下也会发生，因此 HBV 被认为具有直接致癌潜能。HBV 调节蛋白 X (HBx) 已被确定为 HBV 介导的肝癌发生的主要介质。HBV 基因组的一个包含 HBx 编码区的片段通常整合到宿主基因组中，导致产生异常蛋白，随后发生肝癌。此外，HBx 干扰宿主的 DNA 或脱氧核糖核酸损伤修复途径、信号转导、基因表达的表观遗传调控和癌症免疫，从而促进非肝硬化肝脏的癌变。然而，许多分子和途径已被牵连到 HBx 相关 HCC 的发展中，这表明 HBx 介导的肝癌发生的机制仍有待阐明。
