Importance of hepatitis C virus-associated insulin resistance: therapeutic strategies for insulin sensitization

World J Gastroenterol. 2010 Apr 28;16(16):1943-52. doi: 10.3748/wjg.v16.i16.1943.


Insulin resistance is one of the pathological features in patients with hepatitis C virus (HCV) infection. Generally, persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases. However, these complications are not major causes of death in patients with HCV-associated insulin resistance. Indeed, insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection. Mounting evidence indicates that HCV-associated insulin resistance may cause (1) hepatic steatosis; (2) resistance to anti-viral treatment; (3) hepatic fibrosis and esophageal varices; (4) hepatocarcinogenesis and proliferation of hepatocellular carcinoma; and (5) extrahepatic manifestations. Thus, HCV-associated insulin resistance is a therapeutic target at any stage of HCV infection. Although the risk of insulin resistance in HCV-infected patients has been documented, therapeutic guidelines for preventing the distinctive complications of HCV-associated insulin resistance have not yet been established. In addition, mechanisms for the development of HCV-associated insulin resistance differ from lifestyle-associated insulin resistance. In order to ameliorate HCV-associated insulin resistance and its complications, the efficacy of the following interventions is discussed: a late evening snack, coffee consumption, dietary iron restriction, phlebotomy, and zinc supplements. Little is known regarding the effect of anti-diabetic agents on HCV infection, however, a possible association between use of exogenous insulin or a sulfonylurea agent and the development of HCC has recently been reported. On the other hand, insulin-sensitizing agents are reported to improve sustained virologic response rates. In this review, we summarize distinctive complications of, and therapeutic strategies for, HCV-associated insulin resistance. Furthermore, we discuss supplementation with branched-chain amino acids as a unique insulin-sensitizing strategy for patients with HCV-associated insulin resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / virology
  • Cell Proliferation
  • Esophageal and Gastric Varices / virology
  • Fatty Liver / pathology
  • Fibrosis / virology
  • Hepacivirus / metabolism*
  • Hepatitis C / complications*
  • Hepatitis C / immunology
  • Hepatitis C / virology*
  • Humans
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Insulin Resistance*
  • Life Style
  • Liver / pathology
  • Liver Neoplasms / complications
  • Liver Neoplasms / virology


  • Antiviral Agents
  • Insulin