HBV A1762T, G1764A Mutations Are a Valuable Biomarker for Identifying a Subset of Male HBsAg Carriers at Extremely High Risk of Hepatocellular Carcinoma: A Prospective Study

OBJECTIVES: Surveillance of hepatocellular carcinoma (HCC) can detect small tumors for resection but at a huge cost of health resources. The challenge is to reduce the surveillance population. We reported that 96% of HCC patients but only 24% of controls were infected with the hepatitis B virus (HBV) with A(1762)T, G(1764)A mutations in Guangxi, China. It is likely to be extremely beneficial in terms of cost and resources if a significant number of tumors can be detected early by screening this selected population. Our aim is to test this hypothesis. METHODS: A cohort of 2,258 hepatitis B surface antigen-positive subjects aged 30-55 yr was recruited in Guangxi. Following evaluation of virological parameters at baseline, HCC is diagnosed by 6-monthly measurements of serum alpha-fetoprotein levels and ultrasonographic examinations. RESULTS: Sixty-one cases of HCC were diagnosed after 36 months of follow-up. The HCC rate was higher in the mutant than wild-type group (P < 0.001, rate ratio [RR] 6.23, 95% confidence interval [Cl] 2.83-13.68). The HCC rate in the male mutant group was higher than that in the male wild-type group (P < 0.001, RR 11.54, 95% Cl 3.58-37.24). Specifically, 93.3% of male cases are infected with the mutant. Multivariate analyses showed that in men, increasing age and A1762T, G1764A double mutations are independently associated with developing HCC. CONCLUSIONS: HBV A1762T, G1764A mutations constitute a valuable biomarker to identify a subset of male HBsAg carriers aged >30 yr at extremely high risk of HCC in Guangxi, and likely elsewhere.