title: Histologic evidence of active liver injury in chronic hepatitis B patients with normal range or minimally elevated alanine aminotransferase levels.
abstract: OBJECTIVE
  To evaluate the proportion of patients with histologic evidence of active liver disease (HEALD) who have chronic hepatitis B (CHB) and normal/minimally elevated serum alanine aminotransferase (ALT). Sub-analysis was performed to determine whether HEALD based upon liver biopsy better correlates with ALT using modified ALT (30 men/19 women) upper limit of normal (ULN) criteria compared with local conventional laboratory.
  
  
  BACKGROUND
  There are limited data on CHB with normal range ALT (NRALT). We designed a study to evaluate histologic damage in this cohort of patients.
  
  
  METHODS
  A retrospective, multicenter study evaluated CHB patients with normal/minimally elevated ALT [< or = 1.2 x ULN (hepatitis B e antigen positive) or < or = 1.5 x ULN (hepatitis B e antigen negative)]. Liver biopsy specimens were reviewed by an independent histopathologist. HEALD was defined as Knodell necroinflammatory score greater than 5 and Ishak fibrosis stage greater than 1.
  
  
  RESULTS
  Forty-five patients met criteria: median age of 40 years; 51% males; 73% Asian; and 67% hepatitis B e antigen negative. Median hepatitis B virus DNA was 6.04 log10 copies/mL, aspartate aminotransferase (AST) 30 IU/L, and ALT 42 IU/L; and 40% of the patients had ALT greater than ULN. Overall, 20% had HEALD and among patients with NRALT, 4 of 27 (15%) and 0 of 5 (0%) had HEALD through conventional or modified ALT ULN, respectively.
  
  
  CONCLUSIONS
  One fifth of patients with CHB and normal/minimally elevated ALT had HEALD. Among the subset of patients with NRALT, 15% (4 of 27) had HEALD when using conventional laboratory compared with 0% (0 of 5) patients by modified ALT ULN criteria. Use of the modified ALT ULN will likely improve accuracy in identifying patients who may have HEALD compared with conventional laboratory ULN.
authors.affiliation: Division of GI/Hepatology, University of California Irvine School of Medicine, Orange, CA 92868, USA. kqhu@uci.edu
authors.forename: Ke-Qin
authors.initials: KQ
authors.lastname: Hu
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Schiff
authors.forename: Kris V
authors.initials: KV
authors.lastname: Kowdley
authors.forename: Albert D
authors.initials: AD
authors.lastname: Min
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: Lauren O
authors.initials: LO
authors.lastname: Dau
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Peschell
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fagan
authors.forename: John F
authors.initials: JF
authors.lastname: Flaherty
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood; D001706:Biopsy; D002986:Clinical Trials as Topic; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis*; D019694:Hepatitis B, Chronic / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase