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.

Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA before HCC diagnosis. To identify, with a genome-wide approach, additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent nontumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays (Illumina, Inc., San Diego, CA) that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor, compared to nontumor tissues. Array data were validated with pyrosequencing in a subset of five of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37%-63% of cases had detectable hypermethylated DNA (≥5% methylation) for these five genes individually. At least one of these genes was hypermethylated in 87% of the cases, suggesting that measurement of DNA methylation in plasma samples is feasible. Conclusion: The panel of methylated genes indentified in the current study will be further tested in a large cohort of prospectively collected samples to determine their utility as early biomarkers of HCC.

To compare disease recurrence and survival among patients with small hepatocellular carcinoma after surgical resection or percutaneous ethanol injection therapy, 2 treatments that have not been evaluated with a prospective study. A total of 76 patients were randomly assigned to 2 groups based on treatment; all had one or 2 tumors with diameter