Basal core promoter T1762/A1764 and precore A1896 gene mutations in hepatitis B surface antigen-positive hepatocellular carcinoma: a comparison with chronic carriers

Hepatocellular carcinoma (HCC) is a common malignancy in many areas of the world (1). The largest concentrations of HCC cases are in Asia and in Africa, where over 80% of liver cancer cases are reported. In these countries, the most important aetiology for HCC is chronic hepatitis B virus (HBV) infection, and strong geographical correlations have been reported between the incidence of HCC and the prevalence of HBV infections in these areas. The development of chronic HBV infection is dependent on the age of HBV exposure. Up to 90% of infants born to hepatitis B surface antigen (HBsAg)-positive and hepatitis B e antigen (HBeAg)-positive mothers, and 5–10% of adults with acute HBV infection progress to chronic hepatitis B. Thereafter, it is estimated that 15–40% of chronic hepatitis B patients will progress to cirrhosis and to HCC (2). This indicates that 60–85% of HBsAg-positive carriers will have a benign outcome and may remain as inactive carriers with no progression of liver disease. Thus, it is important to identify HBV-infected patients who are at a higher risk for disease progression from those who will not develop decompensated liver disease or HCC. The reasons why some patients with chronic hepatitis B infection progress to HCC are unknown. Host factors such as an immune response to HBV, a genetic predisposition to HCC development, high HBV replication rates, as well as mutations within the HBV genome have been related to HCC development. A dual mutation in the basal core promoter (BCP) region of the HBV genome involving an A–T substitution at nucleotide 1762 and a G–A substitution at nucleotide 1764 has been associated with HCC development (3–5). Also, a mutation in the precore (PC) region of the HBV genome involving a G–A substitution at nucleotide 1896 has been described in patients with HBeAg-negative chronic hepatitis (6). However, its role in HCC pathogenesis is not well established. Studies from Asia have indicated that patients with genotype C are at a higher risk for HCC than patients with other genotypes (7–10). Also, genotype B has been implicated in a younger population of HCC in Taiwan, but in older HCC patients in Japan (7, 8, 11, 12). Recently, elevated serum levels of HBV DNA have been noted to increase the risk for HCC (13–15). In the present report, we compared the baseline hepatitis B virological profiles of 67 chronic carriers who had been followed for a mean of 9 years with no liver complications with 101 HCC patients who were referred to our Liver Center. Our aim was to identify differences in the BCP and PC mutations, HBV genotypes and baseline HBV DNA levels between these two groups of patients who had significantly different clinical outcomes.