Impaction of Viral Load, Genotypes and Viral Mutants on the Risk of HBV Related Hepatocellular Carcinoma (HCC)---Special Emphasis on Early Stage HCC

Hepatitis B virus (HBV) remains the most important risk factor for hepatocellular carcinoma (HCC) worldwide. The relative risk for development of HCC is estimated to be 100 in HBsAg carriers compared to non-carriers of HBsAg. Several non-viral risk factors have been suggested to be associated with an increased the risk of HCC in HBV carriers, including external factors (exposure to aflatoxin, alcohol and cigarette) and host factors (older ages, male gender, severity of underlying liver states, Asian or African ethnicity, family history of HCC). In addition, viral factors (HBV replication, HBV genotype/mutant) have been suggested to be utmost significant in development of HCC. The impact of HBV genotypes on the natural course of chronic HBV infection has been partially clarified. Epidemiological data have shown that genotypes B and C are predominant strains in Taiwan. Genotype B infection is associated with a lower frequency of serum HBeAg, lower serum levels of HBV DNA, a higher and earlier HBeAg seroconversion, and a lower risk of liver cirrhosis and hepatocellular carcinoma, compared to genotype C infection. In addition, genotype C infection is associated with a higher rate of basal core promoter mutation, which has been shown to be associated with the progression of liver disease. Basal core promoter mutation was associated with a 10-fold increased the risk of HCC. More recently, the role of viral load in progression of liver disease also has been reported. Based on these observations, many viral factors may be implicated as risk factors for the development of hepatocellular carcinoma. However, the major limitation of the published studies is analysis of only one for few viral factors each time, rather than simultaneous analysis of all viral factors. Thus, the independent and interactive effects of each factors on the development of hepatocellular carcinoma remains unclear. Furthermore, it remains possible that viral factors may change after the development of hepatocellular carcinoma. Studies of patients with 「early stage」 of hepatocellular carcinoma may be necessary to overcome this problem. In this study, 100 patients with HBV related early hepatocellular carcinoma (solitary tumor ＜3cm) were studied. The controls included 200 age- and sex-matched HBsAg positive carriers without hepatocellular carcinoma. All patients and controls did not have hepatitis C or D virus superinfection. Serum samples at the time of the diagnosis of HCC were collected and tested for viral load, HBV genotypes, precore mutant and core promoter mutant, and the results were compared with HBsAg carriers without HCC.

Project ID:PC9609-3951
External Project ID:NSC96-2628-B182-019