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

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Abstract
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. 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. 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 [CI] 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% CI 3.58-37.24). Specifically, 93.3% of male cases are infected with the mutant. Multivariate analyses showed that in men, increasing age and A(1762)T, G(1764)A double mutations are independently associated with developing HCC. HBV A(1762)T, G(1764)A 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.

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