title: A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B.
abstract: OBJECTIVE
  We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients.
  
  
  METHODS
  From 1994 to 2008, liver biopsy was performed on 319 treatment-naïve CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis.
  
  
  RESULTS
  211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading ≥ 7 or fibrosis score ≥ 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 × upper limit of normal (ULN) and > × 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease.
  
  
  CONCLUSIONS
  An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
authors.forename: Wai-Kay
authors.initials: WK
authors.lastname: Seto
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lai
authors.forename: Philip P C
authors.initials: PP
authors.lastname: Ip
authors.forename: James
authors.initials: J
authors.lastname: Fung
authors.forename: Danny Ka-Ho
authors.initials: DK
authors.lastname: Wong
authors.forename: John Chi-Hang
authors.initials: JC
authors.lastname: Yuen
authors.forename: Ivan Fan-Ngai
authors.initials: IF
authors.lastname: Hung
authors.forename: Man-Fung
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000378:metabolism*; D005260:Female; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase