Familial Risk of Hepatocellular Carcinoma Among Chronic Hepatitis B Carriers and Their Relatives

Background: Familial predisposition as a risk factor for hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) carriers has not been thoroughly explored. Methods: The HCC risk associated with having parents and/or siblings with HCC was evaluated by use of a cohort study of 4808 male HBV carriers. A case–control family study was also conducted on data from first-degree relatives of 553 HBV carriers who had newly diagnosed HCC (case subjects) and 4684 HBV carriers without HCC (control subjects). Results: In the cohort study, HBV carriers with a family history of HCC had a multivariate-adjusted rate ratio for HCC of 2.41 (95% confidence interval [CI] = 1.47–3.95) compared with HBV carriers without a family history of HCC. For carriers with two or more affected relatives, the ratio increased to 5.55 (95% CI = 2.02–15.26). Cumulative HCC risk by age 70 years was 235.6 per 1000 (95% CI = 95.3–375.9 per 1000) for HBV carriers with family history compared with 88.9 per 1000 (95% CI = 67.9–109.9 per 1000) for those without. In the case–control family study, first-degree relatives of case subjects were more likely to have HCC (age–sex-adjusted odds ratio [OR] = 2.57; 95% CI = 2.03–3.25) than first-degree relatives of control subjects. The excess risk of HCC among relatives was particularly evident in siblings (sisters—age-adjusted OR = 4.55 [95% CI = 2.22–9.31]; brothers—age-adjusted OR = 3.73 [95% CI = 2.64–5.27]), but it was also observed in parents. The cumulative risk of HCC to age 80 years was 83.0 per 1000 among relatives of case subjects and 42.0 per 1000 among relatives of control subjects. Among relatives of case subjects, the cumulative risk of HCC was greater if the case subjects were diagnosed before age 50 years (two-sided P = .047). Liver cirrhosis was 2.29 (95% CI = 1.68–3.11) times more frequent in relatives of case subjects than in relatives of control subjects. Conclusions: First-degree relatives of patients with HBV-related HCC appear to be at increased risk of HCC and should be considered in the formulation of HCC-screening programs.