title: High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load.
abstract: OBJECTIVE
  Patients with chronic hepatitis B virus (HBV) infection have a high risk for developing hepatocellular carcinoma (HCC). Patients with lower levels of hepatitis B surface antigen (HBsAg) have higher chances of losing HBsAg than those with high levels. However, little is known about whether higher levels of HBsAg increase risk for HCC.
  
  
  METHODS
  We followed 2688 Taiwanese HBsAg-positive patients without evidence of cirrhosis for a mean time period of 14.7 years. In addition to the known risk factors of HCC, we investigated the association between levels of HBsAg and development of HCC.
  
  
  RESULTS
  Of the patients followed, 191 developed HCC, with an average annual incidence rate of 0.5%. Baseline levels of HBsAg and HBV were associated with development of HCC, and risk increased with level. Compared to HBsAg level, by receiver operating characteristic curve analysis, HBV DNA level better predicted the development of HCC during 10-year and 15-year periods (both, P < .001). However, when we evaluated hepatitis B e antigen-negative patients with levels of HBV DNA <2000 IU/mL, factors that determined HCC risk included sex, age, and levels of alanine aminotransferase and HBsAg (≥1000 IU/mL), but not level of HBV DNA. Multivariate analysis showed that the adjusted hazard ratio for HCC in patients with levels of HBsAg ≥1000 IU/mL versus <1000 IU/mL was 13.7 (95% confidence interval: 4.8-39.3).
  
  
  CONCLUSIONS
  Among patients infected with HBV genotype B or C, determinants of HCC risk include their sex, age, hepatitis B e antigen status, HBV genotype, and levels of alanine aminotransferase and HBV DNA, but not level of HBsAg. Among hepatitis B e antigen-negative patients with low viral loads, HCC risk is determined by levels of HBsAg and alanine aminotransferase and age, but not HBV DNA.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Buddhist Tzu Chi General Hospital Taipei Branch, Taipei, Taiwan.
authors.forename: Tai-Chung
authors.initials: TC
authors.lastname: Tseng
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Yang
authors.forename: Tung-Hung
authors.initials: TH
authors.lastname: Su
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.forename: Chi-Ling
authors.initials: CL
authors.lastname: Chen
authors.forename: Stephanie Fang-Tzu
authors.initials: SF
authors.lastname: Kuo
authors.forename: Chen-Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Pei-Jer
authors.initials: PJ
authors.lastname: Chen
authors.forename: Ding-Shinn
authors.initials: DS
authors.lastname: Chen
authors.forename: Jia-Horng
authors.initials: JH
authors.lastname: Kao
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006513:Hepatitis B e Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase