title: Circulating gamma-glutamyltransferase fractions in cirrhosis.
abstract: OBJECTIVE
  Four gamma-gultamyltransferases (GGT) fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. To assess the behaviour of fractional GGT in cirrhotic patients evaluated for liver transplantation.
  
  
  METHODS
  This was a single-centre, cross-sectional study; GGT fractions were determined by gel-filtration chromatography.
  
  
  RESULTS
  264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), P<0.0001], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), P<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; P<0.05) or total GGT (0.900, 0.869-0.925; P<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum aspartate aminotransferases, alanine aminotransferase, lactate dehydrogenases (LDH), alkaline phosphatases and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with international normalized ratio, bilirubin and LDH.
  
  
  CONCLUSIONS
  The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of aetiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range.
authors.affiliation: Department of Translational Research and Novel Technologies in Medicine and Surgery, University of Pisa, Medical School, Pisa, Italy.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: Elawdi
authors.forename: Maria
authors.initials: M
authors.lastname: Franzini
authors.forename: Aldo
authors.initials: A
authors.lastname: Paolicchi
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Irene
authors.initials: I
authors.lastname: Fornaciari
authors.forename: Vanna
authors.initials: V
authors.lastname: Fierabracci
authors.forename: Paolo
authors.initials: P
authors.lastname: De Simone
authors.forename: Paola
authors.initials: P
authors.lastname: Carrai
authors.forename: Franco
authors.initials: F
authors.lastname: Filipponi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin; D002850:Chromatography, Gel; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007558:Italy; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D001663:Bilirubin
keywords: b-GGT/s-GGT ratio; cirrhosis; end-stage liver disease; fractions; gamma-glutamyltransferase