title: Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk.
abstract: OBJECTIVE
  Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk.
  
  
  METHODS
  Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGT > two fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used.
  
  
  RESULTS
  The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048).
  
  
  CONCLUSIONS
  Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.
authors.affiliation: Department of Gastroenterology, Pasabahce State Hospital, 34800 Istanbul, Turkey. veytahan@yahoo.com
authors.forename: Veysel
authors.initials: V
authors.lastname: Tahan
authors.forename: Billur
authors.initials: B
authors.lastname: Canbakan
authors.forename: Huriye
authors.initials: H
authors.lastname: Balci
authors.forename: Faysal
authors.initials: F
authors.lastname: Dane
authors.forename: Hakan
authors.initials: H
authors.lastname: Akin
authors.forename: Guray
authors.initials: G
authors.lastname: Can
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Hatemi
authors.forename: Vakur
authors.initials: V
authors.lastname: Olgac
authors.forename: Abdullah
authors.initials: A
authors.lastname: Sonsuz
authors.forename: Gulsen
authors.initials: G
authors.lastname: Ozbay
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yurdakul
authors.forename: Hakan
authors.initials: H
authors.lastname: Senturk
mesh_terms: D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D005234:Fatty Liver / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D006505:Hepatitis / Q000097:blood / Q000201:enzymology / Q000209:etiology; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D005723:gamma-Glutamyltransferase