title: Systematic review with meta-analysis: the proportion of chronic hepatitis B patients with normal alanine transaminase ≤ 40 IU/L and significant hepatic fibrosis.
abstract: BACKGROUND
  Chronic hepatitis B (CHB) may lead to cirrhosis, hepatocellular carcinoma and premature death. Elevated alanine transaminase (ALT) levels ≥ the upper limit of normal (ULN) are a major determinant for initiating anti-viral therapy; however, ALT levels alone may not be predictive of hepatic fibrosis.
  
  
  OBJECTIVE
  To determine the proportion of CHB patients with ALT ≤ 40 IU/L and liver fibrosis stage ≥ 2. Secondary goals include subgroup analysis by hepatitis B e antigen (HBeAg) status, high hepatitis B virus (HBV) DNA levels, Asian ethnicity, lower ULN of ≤ 30 IU/L (males) and 19 IU/L (females), and advanced age.
  
  
  METHODS
  Studies identified in EMBASE and MEDLINE (1/1990-6/2012) using the search criteria: "Hepatitis B"[Mesh] OR "Hepatitis B virus"[Mesh] OR "Hepatitis B, Chronic"[Mesh])) AND "Alanine Transaminase"[Mesh]) and abstracts containing the term 'hepatitis' from recent major U.S. gastroenterology and liver society meetings were considered.
  
  
  RESULTS
  Among nine studies (N = 830 patients), a significant proportion (20.7%; 95% CI: 16.2-26.0%) of CHB patients with ALT levels ≤ 40 IU/L had significant fibrosis irrespective of HBeAg status, high HBV DNA levels, ethnicity or age, although this proportion may be higher in patients older than 30-40 years old. The corresponding proportion was 27.8% even when the newer ULN of 30 IU/L (males) and 19 IU/L (females) was applied.
  
  
  CONCLUSIONS
  Approximately one fifth of CHB patients with ALT ≤ 40 IU/L may have significant hepatic fibrosis. The approach to such patients should be individualised, as further evaluation and treatment may be appropriate.
authors.affiliation: Department of Internal Medicine, University of Pittsburgh Medical Center, Shadyside, Pittsburgh, PA, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Chao
authors.forename: J K
authors.initials: JK
authors.lastname: Lim
authors.forename: W S
authors.initials: WS
authors.lastname: Ayoub
authors.forename: L H
authors.initials: LH
authors.lastname: Nguyen
authors.forename: M H
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged
chemical_list: D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase