• biomarker;
  • chromatography;
  • chronic viral hepatitis C;
  • gamma-glutamyltransferase fractions;
  • non-alcoholic fatty liver disease



Serum gamma-glutamyltransferase (GGT) activity is a sensitive but non-specific marker of non-alcoholic fatty liver disease (NAFLD). Recently, four GGT fractions (big-, medium-, small-, free-GGT) were described in humans.


We aimed to investigate whether a specific GGT fraction pattern is associated with NAFLD.


Gamma-glutamyltransferase fractions were determined in patients with NAFLD (n = 90), and compared with those in control subjects (n = 70), and chronic hepatitis C (CHC, n = 45) age and gender matched.


Total GGT was elevated in NAFLD as compared to controls (median, 25°–75°percentile: 39.4, 20.0–82.0 U/L vs. 18.4, 13.2–24.9 U/L respectively, < 0.001). All fractions were higher in NAFLD than in controls (< 0.001). The b-GGT showed the highest diagnostic accuracy for NAFLD diagnosis [area under ROC curve (ROC-AUC): 0.85; cut-off 2.6 U/L, sensitivity 74%, specificity 81%].

Also subjects with CHC showed increased GGT (41.5, 21.9–84.5 U/L, < 0.001 vs. controls, = n.s. vs. NAFLD), as well as m-, s-, and f-GGT, while b-GGT did not show any significant increase (= n.s. vs. HS, < 0.001 vs. NAFLD). In subjects with CHC, s-GGT showed the best diagnostic value (ROC-AUC: 0.853; cut-off 14.1 U/L, sensitivity 73%, specificity 90%). Serum GGT did not show any value in the differential diagnosis between NAFLD and CHC (ROC-AUC 0.507, = n.s.), while b-GGT/s-GGT ratio showed the highest diagnostic accuracy for distinguishing NAFLD and CHC (ROC-AUC: 0.93; cut-off value 0.16, sensitivity 82%, specificity 90%).


b-GGT increases in NAFLD, but not in CHC. GGT fraction analysis might help in improving the sensitivity and specificity of the diagnosis of NAFLD and other liver dysfunctions.