title: Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death.
abstract: OBJECTIVE
  The risk and the predictors of liver disease progression in carriers of inactive hepatitis B virus (HBV) are unclear.
  
  
  METHODS
  Participants in the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus (REVEAL-HBV) study who were seronegative for hepatitis B e antigen; had serum levels of HBV DNA <10,000 copies/mL; and did not have cirrhosis, hepatocellular carcinoma, or increased serum levels of alanine aminotransferase were classified as carriers of inactive HBV (n = 1932). Study participants who were seronegative for HB surface antigen and antibodies against hepatitis C virus, yet had similar clinical liver features, were the controls (n = 18,137). Liver-related death and new cases of hepatocellular carcinoma were ascertained through computerized data linkage with National Cancer Registry and Death Certification profiles. The disease progression rates were estimated. The multivariate-adjusted hazard ratios for risk predictors were derived from Cox regression models.
  
  
  RESULTS
  There were 20,069 participants, contributing a total of 262,122 person-years, with a mean follow-up of 13.1 years. Annual incidence rates of hepatocellular carcinoma and liver-related death were 0.06% and 0.04%, respectively, for inactive HBV carriers; rates were 0.02%, and 0.02% for controls, respectively. The multivariate-adjusted hazard ratios for carriers of inactive HBV, compared to controls, were 4.6 (95% confidence interval: 2.5-8.3) for hepatocellular carcinoma and 2.1 (95% confidence interval: 1.1-4.1) for liver-related death. Older age and alcohol drinking habits were independent predictors of risk for carriers of inactive HBV to develop hepatocellular carcinoma.
  
  
  CONCLUSIONS
  Carriers of inactive HBV have a substantial risk of hepatocellular carcinoma and liver-related death compared with individuals not infected with HBV.
authors.affiliation: Department of Internal Medicine, Bei-Hu Branch, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Jin-De
authors.initials: JD
authors.lastname: Chen
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Uchenna H
authors.initials: UH
authors.lastname: Iloeje
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Su
authors.forename: Chien-An
authors.initials: CA
authors.lastname: Sun
authors.forename: Yun-Fan
authors.initials: YF
authors.lastname: Liaw
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000428:Alcohol Drinking; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000821:virology*; D002353:Carrier State; D016022:Case-Control Studies; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000635:transmission; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000401:mortality / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors; D019562:Viral Load; D038301:Virus Inactivation
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D018937:Hepatitis C Antibodies