title: Synergistic effects of family history of hepatocellular carcinoma and hepatitis B virus infection on risk for incident hepatocellular carcinoma.
abstract: OBJECTIVE
  Little is known about the effects of family history of hepatocellular carcinoma (HCC) on hepatitis B progression or risk of HCC. We examined how family HCC history and presence or stage of hepatitis B virus (HBV) infection affect risk for HCC.
  
  
  METHODS
  We performed a population-based cohort study of 22,472 participants from 7 townships in Taiwan who underwent evaluation for liver disease from 1991 through 1992. Those who received a first diagnosis of HCC from January 1, 1991, to December 31, 2008, were identified from the Taiwanese cancer registry.
  
  
  RESULTS
  There were 374 cases of incident HCC over 362,268 person-years of follow-up evaluation. The cumulative risk of HCC in hepatitis B surface antigen (HBsAg)-seronegative patients without a family history of HCC was 0.62%, in those with a family history of HCC the cumulative risk was 0.65%, in HBsAg-seropositive patients without a family history of HCC the cumulative risk was 7.5%, and in HBsAg-seropositive patients with a family history of HCC the cumulative risk was 15.8% (P < .001). The multivariate-adjusted hazard ratio for HBsAg-seropositive individuals with family history, compared with HBsAg-seronegative individuals without a family history of HCC, was 32.33 (95% confidence interval, 20.8-50.3; P < .001). The relative excess risk owing to interaction was 19, the attributable proportion was 0.59, and the synergy index value was 2.54. These findings indicate synergy between family HCC history and HBsAg serostatus. The synergy between these factors remained significant in stratification analyses by HBeAg serostatus and serum level of HBV DNA.
  
  
  CONCLUSIONS
  Family history of HCC multiplies the risk of HCC at each stage of HBV infection. Patients with a family history of HCC require more intensive management of HBV infection and surveillance for liver cancer.
authors.affiliation: Division of Gastroenterology, University of California at San Diego, La Jolla, California; Division of Epidemiology, University of California at San Diego, La Jolla, California. Electronic address: roloomba@ucsd.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.forename: Jessica
authors.initials: J
authors.lastname: Liu
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Mei-Hsuan
authors.initials: MH
authors.lastname: Lee
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: Uchenna H
authors.initials: UH
authors.lastname: Iloeje
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: David
authors.initials: D
authors.lastname: Brenner
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology*; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D013624:Taiwan / Q000453:epidemiology
keywords: AP; CI; Cancer Risk Factor; Cirrhosis; Epidemiology; HBV; HBeAg; HBsAg; HCC; HR; Liver Disease; RERI; REVEAL; Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus; SI; attributable proportion; confidence interval; hazard ratio; hepatitis B e antigen; hepatitis B surface antigen; hepatitis B virus; hepatocellular carcinoma; relative excess risk caused by interaction; synergy index