Hepatitis B Viral Factors and Long-term Outcomes of Chronic Hepatitis B

Hepatitis B virus (HBV) infection is a global health problem including Taiwan, and more than 350 million people in the world are chronic carriers of the virus. The clinical manifestations of HBV infection range from acute self-limiting infection or fulminant hepatic failure, inactive carrier state, chronic hepatitis with progression to cirrhosis, and hepatocellular carcinoma (HCC). Pathogenesis of HBV infection is usually through the interaction between virus and host immune responses to HBV encoded antigens. Nevertheless, cirrhosis and HCC occur in a small proportion of HBV carriers. It is speculated that HBV-related liver disease progression and hepatocarcinogenesis depend on several predisposing factors, including host and environmental factors such as male gender, older age, late seroconversion of HBeAg, persistence of ALT elevations, co-infection with HCV or HDV, presence of cirrhosis, family history of HCC, obesity, diabetes, cigarette smoking, alcohol drinking and aflatoxin exposure. In addition, it is also important to identify relevant viral factors likely involved in the liver disease progression and HCC development. Recently, viral factors predictive of clinical outcomes have been identified. A large-scale, community cohort studies of Taiwanese HBV carriers indicated that the best predictor of adverse outcomes (cirrhosis and HCC) in chronic HBV infection is the persistent elevation of serum HBV DNA level during follow-up, independent of HBeAg status, ALT level and cirrhosis at study entry. The higher the baseline HBV DNA level, the higher the incidence of adverse outcomes over time. In addition, several hospital-based cohort or case control studies from Taiwan have indicated that baseline HBV DNA level, HBV genotype C, basal core promoter (BCP) T1762/A1764 mutation and possible pre-S deletion mutation are associated with increased risk of liver disease progression as well as HCC development. Our recent studies further indicated that BCP T1762/A1764 mutation is the strongest viral factor associated with both cirrhotic and non-cirrhotic HCC development in HBV carriers. In conclusion, monitoring of serum HBV DNA level and detection of BCP T1762/A1764 mutation in Taiwanese HBV carriers may help identify the high-risk carriers for progression to cirrhosis and HCC, and these carriers should be encouraged to receive antiviral treatment together with a more active surveillance for HCC.