title: Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.
abstract: OBJECTIVE
  Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis.
  
  
  METHODS
  843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and metabolic measurements. IR was diagnosed if HOMA>3. A serum γ-GT concentration of >36 IU/L in females and >61 IU/L in males was considered the threshold value for identifying high levels of γ-GT.
  
  
  RESULTS
  By multivariate logistic regression analysis, abnormal γ-GT serum levels were independently linked to severe liver fibrosis in patients with NAFLD (OR2.711,CI1.120-6.564,p = 0.02), G1CHC (OR3.461,CI2.138-5.603,p<0.001) and CHB (OR2.778,CI1.042-7.414,p = 0.04), together with IR and liver necroinflammation, and with a negative predictive value>80%. Interestingly, among patients with high or normal γ-GT values, even if IR prevalence was significantly higher in patients with severe fibrosis compared to those without, IR remained significantly associated with severe fibrosis in patients with abnormal γ-GT values only (OR4.150,CI1.079-15.970,p = 0.03 for NAFLD; OR2.250,CI1.211-4.181,p = 0.01 for G1CHC; OR3.096,CI2.050-34.220,p = 0.01 for CHB).
  
  
  CONCLUSIONS
  In patients with CLD, IR is independently linked to liver fibrosis only in patients with abnormal γ-GT values, without differences according to liver disease etiology, and suggesting a role of γ-GT as a marker of metabolic-induced liver damage. These data could be useful for the clinical and pharmacologic management of patients with CLD.
authors.affiliation: Sezione di Gastroenterologia, DiBiMIS, University of Palermo, Palermo, Italy. petsa@inwind.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Fabio Salvatore
authors.initials: FS
authors.lastname: Macaluso
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Barcellona
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.forename: Vito
authors.initials: V
authors.lastname: Di Marco
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D002908:Chronic Disease; D015331:Cohort Studies; D003710:Demography; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D005723:gamma-Glutamyltransferase