Antiviral treatment of hepatitis C improves glucose metabolism along the entire spectrum from normal glucose tolerance to diabetes

Background and Aims: Insulin resistance (IR) complicates frequently chronic hepatitis C virus (HCV) infection, leading to an increased incidence of type 2 diabetes mellitus among infected patients. Indeed, it is well known that diabetes control of these patients benefits of successful treatment with either interferon-based regimens or direct antivirals (DAA). Whether the same applies to more subtle alterations of glucose metabolism is unknown. We aimed to fill this gap. Method: The study population included 82 HCV RNA positive patients (48 males, median age 66 years, 73 with advanced fibrosis, 41 HCV-1b), attending the liver clinic of an academic hospital, not previously known to be diabetics. A standard oral glucose tolerance test (OGTT) was performed in all patients before starting DAA treatment and after its conclusion. OGTT results were interpreted according to the American Diabetes Association guidelines. Results: Based on the results of the baseline OGTT, the majority of patients had evidence of abnormal glucose metabolism (N=45,54%; impaired fasting glucose (IFG) 10%, impaired glucose tolerance (IGT) 16%, IFG+IGT 12%, while 17% were diabetics). Conversely, only a minority of them(N=37,45%)were normally glucose tolerant. At the end of treatment, HCV RNA quantification was below the detection threshold (HCV RNA <12 UI/ml), for all the subjects enrolled. A significant decrease in glucose and insulin plasma concentrations was evident both at fasting and after 60 and 120 minutes, leading to a significant reduction in the Homeostasis model assessment (HOMA) IR (from 3.42 [2.66–5.38] to 2.80 [1.78–3.95]); p<0.001 and a corresponding increase in insulin sensitivity (ISI Belfiore from 0.49 [0.26–0.75] to 0.64 [0.42–0.91]; p<0.001) despite a significant reduction in insulin secretion (EFP Stumvoll from 1363.0 [959.2– 1730.0] to 1264.0 [975.8–1588.0]; p=0,027). Moreover, a significant decrease in glycated hemoglobin was observed (p=0.008), and two patients, formerly categorized as diabetics, did not satisfy criteria OGTT for diabetes anymore. The number of patients with normal glucose tolerance increased from 37 (45.1%)to 53 (64.6%); p=0.013), which was paralleled by a reduced number of those satisfying criteria for prediabetic conditions (31 (37.9%) vs.17 (20.8%); p=0.025). Conclusion: After treatment with DAA, glucose metabolism parameters of HCV infected patients improve early and affect the entire pathophysiologic spectrum of glucose metabolism.