X gene mutations in hepatitis B patients with cirrhosis, with and without hepatocellular carcinoma

Specific mutations in the hepatitis B virus (HBV) genome have been reported to be associated with the development of hepatocellular carcinoma (HCC). The goal of this study was to determine whether mutations in the HBV X gene are associated with the development of HCC in hepatitis B patients with cirrhosis. Forty-two patients infected with HBV genotype C2 with cirrhosis and HCC were compared with 46 patients with cirrhosis but without HCC. X gene mutations were determined by direct sequencing in all patients. The HCC and non-HCC groups were similar with respect to clinical characteristics, and the presence of T1762/A1764, T1653, and V1753 mutations was not significantly different between the two groups (P = 0.068, P = 0.097, P = 0.442, respectively). Only the B1499 mutation was associated significantly with HCC (P = 0.015) (odds ratio: 3.42, 95% CI: 1.24-9.48). In hepatitis Be antigen (HBeAg)-positive patients, advanced age was associated significantly with HCC (P = 0.038), whereas in HBeAg-negative patients, the B1499 mutation was associated more significantly with HCC (P = 0.01). Patients in the B1499 mutation group exhibited significantly higher AST and ALT levels compared with patients infected the wild-type virus. In conclusion, B1499 is a novel mutation associated with HCC in Korean patients with cirrhosis infected with HBV genotype C2.