New Insights into HBV Genotypes and HCC

Hepatitis B virus (HBV) is a global health problem. Professor Jia-Horng Kao, from National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan, presented a report on HBV genotypes and HCC. HBV infection causes significant morbidity and mortality, ranging from acute or fulminant hepatitis to end-stage liver disease and hepatocellular carcinoma (HCC). Overall, 75% to 80% of HCC are attributable to persistent viral infections with either HBV (50% to 55%) or hepatitis C virus (HCV) (25% to 30%). Among hepatitis B viral factors predictive of clinical outcomes, HBV viral load, HBV genotype and subgenotype are worthy of attention. According to the heterogeneity of viral sequences, at least 8 HBV genotypes (A to H) are defined by the divergence in entire HBV genomic sequence of greater than 8%. In addition, HBV genotypes can be further subdivided into subgenotypes by at least 4% difference in entire genome sequence. Except for genotype E and G, all genotypes have subgenotypes. Epidemiologic data indicate that in genotypes A, B and C, respective subgenotype A1 (Aa) / A2 (Ae), B1 (Bj) / B2 (Ba) and C1 (Cs) / C2 (Ce) differ widely in many virological aspects.

Professor Kao pointed out that ample clinical evidence had recognized that HBV genotypes influence the natural course of liver disease, especially in Asian countries where genotype B and C prevail. For example, genotype B has been shown to be associated with less progressive liver disease than genotype C, and genotype D has been shown to have a less favorable prognosis than genotype A. However, further studies are needed to examine the clinical impact of each HBV subgenotype on the progression of liver diseases. In the meantime, several case-control and prospective studies revealed that the presence of naturally occurring BCP A1762T/G1764A mutation and pre-S deletion are associated with progressive liver diseases. Of particular note is that combination of mutations rather than single mutation in HBV genome was associated with the development of HCC. In conclusion, on the basis of emerging data, it is recommended that HBV carriers should be routinely genotyped to help identify those who may be at higher risk of liver disease progression and HCC development. In the future, more investigations are needed to clarify the mechanisms involved in HBV genotype-related pathogenesis.