Severity of HCV-induced liver damage alters glucose homeostasis in noncirrhotic patients with chronic HCV infection

Backgroond/Aims: To investigate the link between hepatitis C infection and glucose intolerance, we measured insulin sensitivity, glucose effectiveness and beta-cell secretion in noncirrhotic HCV-infected patients with normal glucose tolerance according to WHO criteria as assessed by oral glucose tol erance tests. Methods: Glucose, insulin and C-peptide data from frequently sampled intravenous glucose tolerance tests were analyzed using the minimal modeling technique for glucose and C-peptide to determine insulin sensitiv ity, glucose effectiveness, first and second phase insulin secretion in non cirrhotic HCV-infected patients (n = 10) and in healthy control subjects (n = 10). Histological activity index (HAI) as well as the extent of fibrosis were evaluated by scoring liver biopsies. Results: Insulin sensitivity (2. 72 +/- 1.63 vs. 6.84 +/- 1.20 10(-4) min(-1) per mu U/ml, p < 0.01) and glu cose effectiveness (2.29 +/- 0.45 vs. 2.89 +/- 0.39 10(-2) min(-1), p<0.05) ere significantly lower in patients with HCV-induced liver disease. Insuli n sensitivity was negatively related to serum alanine aminotransferase (r = -0.47, p < 0.05) and aspartate aminotransferase concentrations (r = -0.65, p < 0.05). Multiple linear regression analysis revealed a strong relation of insulin sensitivity with fibrosis score and HAI (r = -0.82, p < 0.02 for both). Second phase insulin secretion was significantly enhanced in HCV-in fected patients (14.30 +/- 2.04 vs. 8.29 +/- 1.65 min(-1), p < 0.05). Concl usions: HCV-infected patients with normal glucose tolerance are insulin and glucose resistant. The impairment of glucose tolerance appears to be close ly related with the severity of HCV-induced liver damage. Copyright (C) 200 0 S. Karger AG, Basel.