Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2010; 16(16): 1943-1952
Published online Apr 28, 2010. doi: 10.3748/wjg.v16.i16.1943
Importance of hepatitis C virus-associated insulin resistance: Therapeutic strategies for insulin sensitization
Takumi Kawaguchi, Michio Sata
Takumi Kawaguchi, Michio Sata, Department of Digestive Disease Information & Research and Department of Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan
Author contributions: Kawaguchi T and Sata M contributed equally to this paper.
Supported by (in part) A Grant-in-Aid for Young Scientists (B), No. 19790643 to Kawaguchi T and a Grant-in-Aid for Scientific Research (C), No. 21590865 to Sata M, from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labour and Welfare of Japan, and by a Grant for Cancer Research from Fukuoka Cancer Society
Correspondence to: Takumi Kawaguchi, MD, PhD, Assistant Professor, Department of Digestive Disease Information & Research and Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. takumi@med.kurume-u.ac.jp
Telephone: +81-942-317902 Fax: +81-942-317820
Received: January 25, 2010
Revised: February 11, 2010
Accepted: February 18, 2010
Published online: April 28, 2010

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.

Keywords: Hepatitis C virus, Diabetes mellitus, Insulin resistance, Complications, Treatments, Branched-chain amino acid