Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 18, 2016; 8(2): 131-138
Published online Jan 18, 2016. doi: 10.4254/wjh.v8.i2.131
Hepatitis C and insulin action: An intimate relationship
Hilla Knobler, Stephen Malnick
Hilla Knobler, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Rehovot 76100, Israel
Stephen Malnick, Department of Internal Medicine C, Kaplan Medical Center, Rehovot 76100, Israel
Author contributions: Both authors contributed equally to this work.
Conflict-of-interest statement: None of the authors has any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Hilla Knobler, MD, Diabetes and Metabolic Disease Unit, Kaplan Medical Center, Pasternak St., Rehovot 76100, Israel.
Telephone: +972-8-9441650 Fax: +972-8-9441912
Received: July 6, 2015
Peer-review started: July 11, 2015
First decision: September 16, 2015
Revised: December 10, 2015
Accepted: December 29, 2015
Article in press: January 4, 2016
Published online: January 18, 2016

Chronic hepatitis C virus (HCV) infection has been shown to be linked to a higher prevalence of type 2 diabetes compared with the general population or with patients with chronic hepatitis B infection and diabetes is the most common extra-hepatic manifestation of HCV. The HCV-diabetes association is due to insulin resistance (IR) that occurs early in the course of the disease even in patients without or with minimal fibrosis. The mechanisms for HCV-induced IR are only partly understood and include a direct inhibitory effect of HCV on insulin signaling pathway. IR in chronic HCV results in an increased progression rate of hepatic fibrosis, cirrhosis and hepatocellular carcinoma. Some but not all studies found that IR reduces the response rate to interferon/ribavirin therapy. Whether IR affects the response to the new direct-acting antiviral treatments is still unknown.

Keywords: Hepatitis C, Type 2 diabetes, Antiviral therapy, Insulin resistance, Insulin signaling

Core tip: Chronic hepatitis C virus (HCV) infection is associated with a higher prevalence of diabetes as compared to either the general population or patients with chronic hepatitis B infections. HCV hepatitis is linked to insulin resistance (IR) early in the disease course, mediated partly by direct inhibitory effect of the viral proteins on insulin signaling. The presence of IR is associated with an increased rate of disease progression to fibrosis, cirrhosis and hepatocellular carcinoma. Interferon and ribavirin treatment of HCV hepatitis may be less successful in the presence of IR. The effect of IR on the new direct-acting antiviral treatment is unclear.