title: Updated thresholds for alanine aminotransferase do not exclude significant histological disease in chronic hepatitis C.
abstract: OBJECTIVE
  Histological changes in hepatitis C virus (HCV)-infected patients with persistently normal alanine aminotransferase (PNALT) have not been evaluated for updated upper limits of normal (ULN; ≤ 19/30 U/L for females/males). We assessed significant fibrosis (≥ F2, METAVIR) in patients with PNALT and persistently elevated alanine aminotransferase (PEALT).
  
  
  METHODS
  Nine hundred and twenty consecutive, unselected HCV patients were stratified into four groups: Group I: (n = 124) PNALT within the updated ULN [0.5 × ULN (corresponding to ≤ 19 U/L) for females; 0.75 × ULN (corresponding to ≤ 30 U/L) for males]; Group II (n = 173): PNALT ≤ 1 × ULN but greater than Group I; Group III (n = 313): PEALT 1-2 × ULN; and Group IV (n = 310): PEALT > 2 × ULN. PNALT was defined as ≥ 3 determinations within the normal range over ≥ 6 months.
  
  
  RESULTS
  Advanced ≥ F3 and ≥ F2 fibrosis increased incrementally across Groups I; II; III; and IV: 24.2 and 45.2%; 25.4 and 56.1%; 36.1 and 64.2%; and 50 and 77.1% respectively (P<0.0001 for both). Multivariable logistic regression analysis identified age [odds ratio (OR), 1.05; 95% confidence intervals (CI): 1.02-1.08; P<0.0001], alanine aminotransferase (ALT) groups (OR 1.38; 95% CI: 1.03-1.83; P = 0.030), presence of moderate-severe steatosis (OR 2.70; 95% CI: 1.19-6.15; P = 0.018) and ≥ A2 necroinflammation (OR 17.9; 95% CI: 8.88-36.20; P < 0.0001) as independent predictors of ≥ F2 fibrosis. Updated ULN for ALT were better at excluding ≥ F2 fibrosis compared with traditional ULN (90.6 vs. 74.2%, P = 0.0041) but less specific (20.8 vs. 44%, P = 0.0007) with similar positive/negative predictive values.
  
  
  CONCLUSIONS
  HCV patients with 'updated' normal ALT have the lowest prevalence of significant fibrosis, although utilizing these levels without resorting to biopsy would miss significant fibrosis in almost one-half of such patients.
authors: Department of Medicine, Division of Hepatology, Riyadh Military Hospital, Riyadh, Saudi Arabia. sanaifa@ngha.med.sa
authors: Faisal M
authors: FM
authors: Sanai
authors: Ahmed
authors: A
authors: Helmy
authors: Cheryl
authors: C
authors: Dale
authors: Hamad
authors: H
authors: Al-Ashgar
authors: Ayman A
authors: AA
authors: Abdo
authors: Kazuhiro
authors: K
authors: Katada
authors: Hadeel
authors: H
authors: AlMana
authors: Mayssa
authors: M
authors: Saadeh
authors: Hussa
authors: H
authors: Al-Hussaini
authors: Mohammed
authors: M
authors: AlQuaiz
authors: Ahmed
authors: A
authors: Hashem
authors: Khalid
authors: K
authors: AlSwat
authors: Khalid I
authors: KI
authors: Bzeizi
authors: Paul J
authors: PJ
authors: Marotta
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism* / Q000592:standards; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000201:enzymology*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology*; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D012372:ROC Curve
chemical_list: D000410:Alanine Transaminase