The Effect of HBV Genotype C on the Development of HCC Differs Between Wild-Type Viruses and Those With BCP Double Mutations (T1762A1764)

BACKGROUND Association of hepatitis B virus (HBV) genotype C with hepatocellular carcinoma (HCC) development remains controversial. HBV basal core promoter (BCP) double mutations (T(1762)A(1764)) are very strong confounding factors of genotypes B and C in HCC development. OBJECTIVES To investigate the association of HBV genotype C with HCC development after controlling for BCP double mutations. MATERIALS AND METHODS Four hundred and two serum samples from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH) and also from asymptomatic HBsAg carriers were analyzed. RESULTS Genotypes B (31.1%), C (62.8%), and I (6.1%) were detected. With the severity of liver disease the prevalence of genotype B decreased, but genotype C increased. No trend was found for genotype I. The prevalence of BCP double mutations in genotypes C and I viruses was significantly higher than genotype B. BCP double mutations are risk factors for CH, LC and HCC. Genotype C was not identified as a particular risk factor for HCC prior to the stratification analysis but after that genotype C viruses with BCP double mutations were found to be a particular risk factor for HCC (P = 0.008, OR = 17.19 [95% CI: 2.10 - 140.41]), but those with the wild-type BCP were not. In the interaction analysis, genotype C and BCP double mutations were found to have a synergistic effect on HCC development (P < 0.0001, OR = 52.56 [95% CI: 11.49-240.52]). CONCLUSIONS The effect of HBV genotype C on the development of HCC differs between wild-type viruses and those with BCP double mutations, suggesting that not all individuals infected with genotype C HBV are at increased risk of HCC.