Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States.

Abstract

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated. Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared. Forty-four of 173 (25.4%) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1%) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2±10.3years vs. 63.0±6.8years, p<0.001 and 41.2±14.8years vs. 60.5±5.5years, p=0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6%) tested were HBsAg positive and 14 (63.6%) had HCC; in fathers, 11/21 (52.4%) tested were HBsAg positive and 10 (90.9%) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR=2.58, p=0.05), male gender (OR=3.23, p=0.03), cirrhosis (OR=2.4, p=0.04), Child-Pugh classification (OR=7.62, p=0.004), AFP per log10 increase (OR=1.68, p=0.01), precore mutation (OR=3.77, p=0.003), and basal core promoter mutation (OR=8.33, p<0.001). HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.