title: Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States.
abstract: OBJECTIVE
  The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA. myrontong@hmri.org.|Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. myrontong@hmri.org.
authors.forename: Myron John
authors.initials: MJ
authors.lastname: Tong
authors.affiliation: Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA.
authors.forename: Thatcher Thi
authors.initials: TT
authors.lastname: Huynh
authors.affiliation: Liver Center, Huntington Medical Research Institutes, 660 South Fair Oaks Avenue, Pasadena, CA, 91105, USA.|Pfleger Liver Institute and the Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.|Chalubhorn Hospital, Bangkok, Thailand.
authors.forename: Surachate
authors.initials: S
authors.lastname: Siripongsakun
keywords: Familial clustering; Hepatitis B; Hepatocellular carcinoma