Editorial
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 28, 2006; 12(44): 7075-7080
Published online Nov 28, 2006. doi: 10.3748/wjg.v12.i44.7075
Insulin resistance and hepatitis C
Manuel Romero-Gómez
Manuel Romero-Gómez, Unit for the Clinical Management of Digestive Diseases. Hospital Universitario de Valme. Ctra de Cádiz s/n 41014, Sevilla, Spain
Supported by a grant of PAI-CTS-532 from Junta de Andalucía, Andalucía, Spain
Correspondence to: Manuel Romero-Gómez, MD, Unit for The Clinical Management of Digestive Diseases. Hospital Universitario de Valme. Ctra de Cadiz s/n. Sevilla 41014, Spain. mromerog@supercable.es
Telephone: +34-955-015761 Fax: +34-955-015899
Received: July 18, 2006
Revised: July 28, 2006
Accepted: August 29, 2006
Published online: November 28, 2006
Abstract

Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients. Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: “viral” and “metabolic” insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARγ receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American. Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin. Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7 cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance, steatosis and fibrosis progression.

Keywords: Diabetes mellitus; Homeostasis model of assessment; Fibrosis; Steatosis; Sustained response; Peginterferon; Ribavirin