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

Abstract

BackgroundThe 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.MethodsThe 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.ResultsAt 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).ConclusionsGlucose 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.

Hepatitis C virus eradication with direct‐acting antiviral improves insulin resistance

“…After the widespread adoption of highly effective direct‐acting antivirals (DAAs), preliminary data from case series and cohort studies confirmed what previously described in the IFN era . However, most of them were mono‐centric and/or retrospective, with a relatively short duration of follow‐up.…”

“…Hepatitis C virus can interfere with glucose homeostasis in different ways, most of which involving insulin signalling . Multiple and synergistic mechanisms are implied: degradation of insulin receptor substrate‐1 (IRS‐1), inhibition of insulin activity, increased glucose synthesis and release from hepatocytes .…”

Hepatitis C Virus Clearance with Glucose Improvement and Factors Affecting the Glucose Control in Chronic Hepatitis C Patients

“…Meanwhile, in patients without T2DM, Luigi E. Adinolfi et al conducted a prospective case-control study that enrolled 133 consecutive HCV patients with advanced liver fibrosis (F3-F4) and showed that viral eradication by DAAs reduced HOMA-IR and serum glucose, while no variation occurred in untreated patients after SVR12 34 . In addition, a recent report from Alessandro Gualerzi et al found similar results, showing that an improvement in glucose metabolism occurred both in diabetes and non-diabetes patients after antiviral treatment by DAAs 35 . As a result, The eradication of HCV may improve glycometabolism, regardless of the treatment regime with PR or DAAs.…”

“…Insulin resistance did not impair the response of CHC patients treated with DAAs 29 . Currently, many studies on DAA treatments for HCV have also demonstrated the potential benefit in glucose metabolism after SVR [30][31][32][33][34][35][36] . A retrospective single-center observational study from Philip Weidner et al investigated 281 patients receiving DAA ± Ribavirin and measured FPG.…”

The Effect of Viral Clearance Achieved by Direct-Acting Antiviral Agents on Hepatitis C Virus Positive Patients with Type 2 Diabetes Mellitus: A Word of Caution after the Initial Enthusiasm

“…Improvement of IR appeared independent of fibrosis severity and body mass index (BMI) value. Gualerzi et al [39] prospectively analyzed 82 HCV-RNA-positive nondiabetic patients, most with cirrhosis, who were treated with DAAs. Before and immediately after antiviral therapy, all underwent a standard oral glucose tolerance test (OGTT); the OGTT-derived indices were homeostasis model assessment (HOMA)-IR and insulin sensitivity index (ISI).…”