Interferon-alpha improves glucose tolerance in diabetic and non-diabetic patients with HCV-induced liver disease

This pilot study was initiated to evaluate factors controlling glucose tolerance in patients with hepatitis C virus-induced liver disease before and after therapy with recombinant interferon-alpha (r-INF-alpha). Fifteen patients with histologically and serologically proven hepatitis C infection underwent oral and frequently sampled intravenous glucose tolerance tests (FSIGTT) before and after four months of therapy (6 x 106 U r-INF-alpha, subcutaneously, three times a week). Glucose, insulin and C-peptide data from FSIGTT were analysed using the minimal modeling technique to determine insulin sensitivity, glucose effectiveness and first and second phase insulin secretion. According to the WHO criteria 13 patients, had normal glucose tolerance; diabetes mellitus was diagnosed in 2 patients. In the morning following the last r-INF-alpha injection four months later, insulin sensitivity improved significantly in hepatitis C virus-infected patients with normal glucose tolerance (2.17 +/- 0.37 vs. 6.18 +/- 0.94 10(-4) min(-1) per microU/ml, p < 0.001) and with diabetes mellitus (0.86 to 2.61; 0.46 to 1.06 10(-4) min(-1) per microU/ml). This effect was independent of the extent of fibrosis, virus load before treatment and therapy response. First phase insulin secretion increased in non-diabetic (139.2 +/- 17.1 vs. 200.0 +/- 32.7, p < 0.05) and diabetic patients with HCV infection (55.24 to 118.5; 84.23 to 261.1). Moreover, free fatty acid concentrations in all HCV-infected patients were significantly reduced (0.48 +/- 0.01 vs 0.21 +/- 0.03 mmol/l, p < 0.01). Therapy with recombinant interferon-alpha is associated with an amelioration of glucose tolerance in non-diabetic and diabetic HCV-infected patients.