Declaration of conflict of interestHLY Chan is an advisory board member of Bristol-Myers Squibb, F. Hoffmann La-Roche, Novartis Pharmaceutical and Abbott Diagnostic.
Significance of hepatitis B virus genotypes and mutations in the development of hepatocellular carcinoma in Asia
Version of Record online: 22 DEC 2010
© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 26, Issue 1, pages 8–12, January 2011
How to Cite
Chan, H. L.-Y. (2011), Significance of hepatitis B virus genotypes and mutations in the development of hepatocellular carcinoma in Asia. Journal of Gastroenterology and Hepatology, 26: 8–12. doi: 10.1111/j.1440-1746.2010.06514.x
The emerging leadership lectures at each APDW are educational activities sponsored by the JGH Foundation
- Issue online: 22 DEC 2010
- Version of Record online: 22 DEC 2010
- Accepted manuscript online: 28 SEP 2010 06:40PM EST
- Accepted for publication 12 September 2010.
- core promoter;
- hepatitis B virus;
- hepatocellular carcinoma;
Advances in molecular biology technology in the last two decades have allowed detailed study of the viral mutations and genomic heterogeneity of hepatitis B virus (HBV). The first mutant discovered was precore stop codon mutation. It was reported in HBeAg-negative patients and initially thought to associate with fulminant hepatitis. Subsequent studies have suggested that it is merely one of the mechanisms of losing HBeAg by the virus. Another mutation that can downregulate the production of HBeAg is the basal core promoter mutation, which is located in the X gene upstream of the precore region. Based on the configuration of codon 15 and the stability of the epsilon of the precore region, these two mutants will be differentially selected during the course of HBeAg seroconversion. The most common HBV genotypes in South-East Asia are genotype B and C HBV. The higher hepatocellular carcinoma (HCC) risk of genotype C HBV has been confirmed by longitudinal studies in Hong Kong and Taiwan. One possible carcinogenic mechanism is its association with basal core promoter mutation, which has also been found to be a risk factor of HCC. Within genotype C HBV, subgenotype Cs is predominant in South-East Asia and subgenotype Ce is predominant in East Asia. Subgenotype Ce HBV has been found to have the highest risk of HCC as compared with subgenotype Cs or genotype B HBV. The understanding of the carcinogenic mechanisms of these HBV strains may shed light into future therapeutics in the prevention and treatment of HBV-related HCC.