Improvement of insulin sensitivity in diabetic and non diabetic patients with chronic hepatitis C treated with direct antiviral agents

Background: The increased incidence of type 2 diabetes mellitus among hepatitis C virus (HCV) infected patients is likely due to viral-induced insulin resistance (IR). Indeed, control of diabetes in these patients benefits of successful antiviral treatment; whether the same applies to subtler alterations of glucose metabolism is unknown. We aimed to fill this gap. Methods: 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 to receive direct antivirals. None was previously known to be diabetic. All underwent a standard oral glucose tolerance test (OGTT) before antiviral treatment and right after its conclusion. Results: At baseline, the majority of patients had evidence of abnormal glucose metabolism (N. = 45, 55%; impaired fasting glucose 10%, impaired glucose tolerance16%, both the above 12%, 17% diabetes), while only 37 (45%) were normally glucose tolerant (NGT). At the end of treatment, HCV-RNA quantification was below the detection threshold (HCV-RNA <12 UI/ ml), for all patients enrolled. A significant decrease in glucose and insulin plasma concentrations was observed, leading to a significant reduction in 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 [959-1730] to 1264 [976-1588];p = 0.027). Importantly, HOMA-IR reduction occurred also in the subgroup of NGT patients (p = 0.017). The number of NGT patients increased to 53, 65% (p = 0.013) paralleled by a reduced number of those satisfying criteria for prediabetic conditions (31 (38%) vs. 17 (21%); p = 0.025). Conclusions: Glucose metabolism parameters of HCV infected patients improve early after antiviral treatment, with benefits that are not limited to diabetics. These findings confirm how deep and widespread is the impairment of insulin pathways exerted by HCV infection.