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Eradicating hepatitis C virus ameliorates insulin resistance without change in adipose depots

Lookup NU author(s): Professor Mike TrenellORCiD


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Chronic hepatitis C (CHC) is associated with lipid-related changes and insulin resistance; the latter predicts response to antiviral therapy, liver disease progression and the risk of diabetes. We sought to determine whether insulin sensitivity improves following CHC viral eradication after antiviral therapy and whether this is accompanied by changes in fat depots or adipokine levels. We compared 8 normoglycaemic men with CHC (genotype 1 or 3) before and at least 6months post viral eradication and 15 hepatitis C antibody negative controls using an intravenous glucose tolerance test and two-step hyperinsulinaemic-euglycaemic clamp with [6,6-H-2(2)] glucose to assess peripheral and hepatic insulin sensitivity. Magnetic resonance imaging and spectroscopy quantified abdominal fat compartments, liver and intramyocellular lipid. Peripheral insulin sensitivity improved (glucose infusion rate during high-dose insulin increased from 10.1 +/- 1.6 to 12 +/- 2.1mg/kg/min/, P=0.025), with no change in hepatic insulin response following successful viral eradication, without any accompanying change in muscle, liver or abdominal fat depots. There was corresponding improvement in incremental glycaemic response to intravenous glucose (pretreatment: 62.1 +/- 8.3 vs post-treatment: 56.1 +/- 8.5mm, P=0.008). Insulin sensitivity after viral clearance was comparable to matched controls without CHC. Post therapy, liver enzyme levels decreased but, interestingly, levels of glucagon, fatty acid-binding protein and lipocalin-2 remained elevated. Eradication of the hepatitis C virus improves insulin sensitivity without alteration in fat depots, adipokine or glucagon levels, consistent with a direct link of the virus with insulin resistance.

Publication metadata

Author(s): Milner KL, Jenkins AB, Trenell M, Tid-Ang J, Samocha-Bonet D, Weltman M, Xu A, George J, Chisholm DJ

Publication type: Article

Publication status: Published

Journal: Journal of Viral Hepatitis

Year: 2014

Volume: 21

Issue: 5

Pages: 325-332

Print publication date: 12/08/2013

ISSN (print): 1352-0504

ISSN (electronic): 1365-2893

Publisher: Wiley-Blackwell


DOI: 10.1111/jvh.12143


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Funder referenceFunder name
Robert W. Storr Bequest
Diabetes UK RD Lawrence Fellowship
National Health and Medical Research Council Postgraduate scholarship
University of Sydney
358398National Health and Medical Research Council of Australia
HKU 2/07CHong Kong Research Council CRF