Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

Abstract

Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62±7.4years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5±7.1 vs 102.8±7.2mg/dL, P=.15) but 2-hour plasma glucose was reduced (165.2±22.7 vs 138.5±21.3mg/dL, P<.001). Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1±0.2% vs 5.7±0.3%, P<.001) and post-load insulin resistance as assessed by the oral glucose insulin sensitivity index (6.92±1.56 vs 9.52±1.39mg/kg/min, P<.001). These effects were observed despite no change in body mass index from baseline to follow-up (25.6±4.3 vs 25.8±4.4, P>.5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis.