title: Hepatitis B virus DNA prediction rules for hepatitis B e antigen-negative chronic hepatitis B.
abstract: After hepatitis B e antigen (HBeAg) seroconversion, hepatitis B may become inactive or progress to HBeAg-negative hepatitis with persistent or intermittent alanine aminotransferase (ALT) elevation. The aim of this study was to prospectively identify factors predictive of the clinical course in HBeAg-negative chronic hepatitis B (CHB). Patients were stratified by ALT and HBeAg status and followed every 3 months for up to 5 years. Kaplan-Meier and Cox regression analysis using the change from normal ALT to elevated ALT as endpoints were performed to determine factors associated with ALT elevation/normalization. Seventy-four HBeAg-negative and 32 HBeAg-positive patients were prospectively evaluated. For HBeAg-negative patients, hepatitis B virus (HBV) DNA was predictive of future ALT. Only 1 patient with normal ALT and an HBV DNA value lower than 10,000 copies/mL developed an elevated ALT within the subsequent year, whereas 67% with an HBV DNA value greater than 100,000 copies/mL had a rise in ALT above normal within 1 year. Patients with a previous history of ALT elevation and longer follow-up at all levels of HBV DNA were more likely to experience ALT elevations. For HBeAg-negative patients with elevated ALT and all HBeAg-positive patients, HBV DNA did not predict future ALT. Other viral and host factors were not predictive of future ALT.
  
  
  CONCLUSIONS
  HBeAg-negative CHB has a fluctuating course. HBV DNA values lower than 10,000 copies/mL predict persistently normal ALT for at least 1 year. Patients with HBV DNA values between 10,000 and 100,000 copies/mL can safely be followed at 6 monthly intervals, whereas HBV DNA values greater than 100,000 copies/mL are highly predictive of future ALT elevation and should prompt regular follow-up.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Canada. feldj@niddk.nih.gov
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.forename: Melissa
authors.initials: M
authors.lastname: Ayers
authors.forename: Dahlia
authors.initials: D
authors.lastname: El-Ashry
authors.forename: Tony
authors.initials: T
authors.lastname: Mazzulli
authors.forename: Raymond
authors.initials: R
authors.lastname: Tellier
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D015331:Cohort Studies; D004279:DNA, Viral / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood* / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase