Semin Liver Dis 2021; 41(02): 142-149
DOI: 10.1055/s-0041-1723033
Review Article

Potential of HBx Gene for Hepatocarcinogenesis in Noncirrhotic Liver

Kazuma Sekiba
1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
2   Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
Motoyuki Otsuka
1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Kazuhiko Koike
1   Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
› Author Affiliations
Funding Japan Agency for Medical Research and Development, AMED, JP20fk0210054, JP20fk0210080h0001, JP20fk0310102. The Ministry of Education, Culture, Sports, Science, and Technology, Japan, 19H03430, 19J11829.


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.

Publication History

Article published online:
06 May 2021

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