title: Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma.
abstract: OBJECTIVE
  It is not clear whether risk for hepatocellular carcinoma can be accurately determined from long-term changes in serum levels of hepatitis B virus (HBV) DNA or alanine aminotransferase (ALT).
  
  
  METHODS
  We measured serum levels of HBV DNA and ALT at enrollment and during follow-up analysis of 3160 participants in the REVEAL-HBV study. Development of hepatocellular carcinoma was determined from follow-up examinations and computerized linkage with National Cancer Registry and National Death Certification profiles. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.
  
  
  RESULTS
  During 38,330 person-years of follow-up, 81 participants developed hepatocellular carcinoma (incidence rate, 211.3/100,000 person-years). The risk for hepatocellular carcinoma was only slightly higher for participants whose follow-up levels of HBV DNA spontaneously decreased to <10,000 copies/mL compared with those with baseline levels of HBV DNA<10,000 copies/mL (control group; HR, 2.25; 95% CI, 0.68-7.37). Compared with the control group, the HRs (95% CI) for long-term levels of HBV DNA that persisted at 10,000 to 100,000 copies/mL, decreased to/persisted at 100,000 to 1,000,000 copies/mL, or decreased to/persisted at 1,000,000 to 10,000,000 copies/mL were 3.12 (1.09-8.89), 8.85 (3.85-20.35), and 16.78 (7.33-38.39), respectively. A gradient in ALT level was significantly associated with hepatocellular carcinoma risk: from all low-normal, to ever high-normal, to transient abnormal, to persistent abnormal (Ptrend<.001).
  
  
  CONCLUSIONS
  Long-term changes in serum levels of HBV DNA and ALT are independent predictors of risk for hepatocellular carcinoma. Regular monitoring of levels of HBV DNA and ALT is important in clinical management of chronic carriers of HBV.
authors.affiliation: Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, and Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Chuen-Fei
authors.initials: CF
authors.lastname: Chen
authors.forename: Wen-Chung
authors.initials: WC
authors.lastname: Lee
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Hung-Chuen
authors.initials: HC
authors.lastname: Chang
authors.forename: Chin-Lan
authors.initials: CL
authors.lastname: Jen
authors.forename: Uchenna H
authors.initials: UH
authors.lastname: Iloeje
authors.forename: Jun
authors.initials: J
authors.lastname: Su
authors.forename: Chuhsing K
authors.initials: CK
authors.lastname: Hsiao
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Wang
authors.forename: San-Lin
authors.initials: SL
authors.lastname: You
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Lu
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D000410:Alanine Transaminase