Clearance of HCV improves insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate 1 and 2

Am J Gastroenterol. 2007 Mar;102(3):570-6. doi: 10.1111/j.1572-0241.2006.01038.x.


Objectives: Hepatitis C virus (HCV) infection is linked to greater insulin resistance. Although HCV itself is a candidate for the development of insulin resistance, the effects of antiviral treatment on impaired glucose metabolism remain unclear. The aim of this study is to examine the effects of clearance of HCV on insulin resistance, beta-cell function, and hepatic expression of insulin receptor substrate (IRS)1/2, central molecules for insulin signaling.

Methods: We analyzed 89 biopsy-proven patients with chronic HCV infection. Patients received interferon-alpha or interferon-alpha plus ribavirin for 6 months and were classified into three groups at 6 months after the conclusion of antiviral therapy according to their response to antiviral therapy: sustained responders (N = 29), relapsers (N = 12), and nonresponders (N = 48). Insulin resistance and beta-cell function were assessed by the homeostasis model assessment method (HOMA-IR and HOMA-%B, respectively). Hepatic expression of IRS1/2 was evaluated by immunoblotting and immunostaining in 14 sustained responders.

Results: In nonresponders and relapsers, there were no significant changes in HOMA-IR and HOMA-%B values after antiviral therapy. On the other hand, in sustained responders, HOMA-IR values significantly decreased to 1.7 +/- 0.8 from 3.1 +/- 1.1 (P < 0.05) after antiviral therapy. Similarly, HOMA-%B values significantly decreased to 90.6 +/- 10.0 from 113.7 +/- 15.3 (P < 0.05). Immunoblotting showed a threefold increase in IRS1/2 expression after clearance of HCV. Immunostaining revealed that greater IRS1/2 expression was seen in hepatocytes.

Conclusions: We showed that clearance of HCV improves insulin resistance, beta-cell function, and hepatic IRS1/2 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Female
  • Follow-Up Studies
  • Gene Expression*
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification*
  • Hepatitis C / metabolism
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology
  • Intracellular Signaling Peptides and Proteins
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Middle Aged
  • Phosphoproteins / biosynthesis*
  • Prognosis
  • RNA, Viral / analysis
  • Receptor, Insulin / biosynthesis
  • Viral Load


  • IRS1 protein, human
  • IRS2 protein, human
  • Insulin Receptor Substrate Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • RNA, Viral
  • Receptor, Insulin