Importance of hepatitis C virus-associated insulin resistance: therapeutic strategies for insulin sensitization.
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.
Kawaguchi
Takumi
T
Department of Digestive Disease Information & Research and Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Japan. takumi@med.kurume-u.ac.jp
Sata
Michio
M
D000998:Antiviral Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000821:virology; D049109:Cell Proliferation; D004932:Esophageal and Gastric Varices / Q000821:virology; D005234:Fatty Liver / Q000473:pathology; D005355:Fibrosis / Q000821:virology; D016174:Hepacivirus / Q000378:metabolism*; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology / Q000821:virology*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D007333:Insulin Resistance; D008019:Life Style; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000150:complications / Q000821:virology
D000998:Antiviral Agents; D007328:Insulin