Hepatitis C Virus Infection Can Present with Metabolic Disease by Inducing Insulin Resistance

Although hepatitis C virus (HCV) targets the liver, it has become increasingly evident that HCV can induce diseases of many organs. Recently, much attention is drawn to metabolic disorders in HCV infection. First, hepatic steatosis and derangement in lipid metabolism have been found characteristic of HCV infection, and later on, a correlation was noted between HCV infection and diabetes as well as insulin resistance. We have demonstrated that HCV by itself can induce insulin resistance through disturbing the insulin signaling pathway by HCV proteins. The fact that HCV infection induces insulin resistance by the virus itself may influence the progression of chronic liver disease and open up novel therapeutic approaches. In conclusion, towards the future, HCV infection needs to be viewed not only as a liver disease but also as a metabolic disease.

[1]  M. Houghton,et al.  Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. , 1989, Science.

[2]  M. Onji,et al.  Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Rapicetta,et al.  Hepatitis C Virus Infection as a Risk Factor for Hepatocellular Carcinoma in Patients with Cirrhosis , 1992, Annals of Internal Medicine.

[4]  R. Chung,et al.  A role for hepatitis C virus infection in type II cryoglobulinemia. , 1992, The New England journal of medicine.

[5]  F. Schaffner,et al.  The histological features of chronic hepatitis C and autoimmune chronic hepatitis: A comparative analysis , 1992, Hepatology.

[6]  D. Pateron,et al.  Lymphocytic sialadenitis of Sjögren's syndrome associated with chronic hepatitis C virus liver disease , 1992, The Lancet.

[7]  A. Baker A role for hepatitis C virus infection in type II cryoglobulinemia Agnello V., Chung R.T., Kaplan L.M. N Engl J Med 1992;327:1490–1495 , 1993 .

[8]  E. Schiff,et al.  Pathological diagnosis of chronic hepatitis C: a multicenter comparative study with chronic hepatitis B. The Hepatitis Interventional Therapy Group. , 1993, Gastroenterology.

[9]  R. Rodby,et al.  Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. , 1993, Journal of the American Society of Nephrology : JASN.

[10]  C. Palmer,et al.  Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. , 1994, Journal of hepatology.

[11]  J. Pawlotsky,et al.  Lichen planus and hepatitis C virus (HCV)‐related chronic hepatitis: evaluation of HCV genotypes , 1995, The British journal of dermatology.

[12]  K. Koike,et al.  Sialadenitis histologically resembling Sjogren syndrome in mice transgenic for hepatitis C virus envelope genes. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K Koike,et al.  Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. , 1997, The Journal of general virology.

[14]  B. Kahn Type 2 Diabetes: When Insulin Secretion Fails to Compensate for Insulin Resistance , 1998, Cell.

[15]  Yoshiharu Matsuura,et al.  The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice , 1998, Nature Medicine.

[16]  M. Szklo,et al.  Prevalence of Type 2 Diabetes Mellitus among Persons with Hepatitis C Virus Infection in the United States , 2000, Annals of Internal Medicine.

[17]  T. Takayama,et al.  Normalization of elevated hepatic 8-hydroxy-2'-deoxyguanosine levels in chronic hepatitis C patients by phlebotomy and low iron diet. , 2001, Cancer research.

[18]  B. Bacon,et al.  Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C , 2001, American Journal of Gastroenterology.

[19]  M. Honda,et al.  Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. , 2002, Gastroenterology.

[20]  P. Farci,et al.  Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome [Science 1989;244:359-362]. , 2002, Journal of hepatology.

[21]  K. Koike,et al.  Alteration of intrahepatic cytokine expression and AP-1 activation in transgenic mice expressing hepatitis C virus core protein. , 2002, Virology.

[22]  David Bernstein,et al.  Impaired IRS‐1/PI3‐kinase signaling in patients with HCV: A mechanism for increased prevalence of type 2 diabetes , 2003, Hepatology.

[23]  K. Koike,et al.  Serum lipid profile of patients with genotype 1b hepatitis C viral infection in Japan. , 2003, Hepatology research : the official journal of the Japan Society of Hepatology.

[24]  J. Gisbert,et al.  Prevalence of hepatitis C virus infection in B-cell non-Hodgkin's lymphoma: systematic review and meta-analysis. , 2003, Gastroenterology.

[25]  Douglas L. Rothman,et al.  Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance , 2003, Science.

[26]  J. Kench,et al.  Insulin resistance is associated with chronic hepatitis C and virus infection fibrosis progression , 2003 .

[27]  K. Koike,et al.  Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. , 2004, Gastroenterology.

[28]  M. Matsuhisa,et al.  Both Insulin Signaling Defects in the Liver and Obesity Contribute to Insulin Resistance and Cause Diabetes in Irs2–/– Mice* , 2004, Journal of Biological Chemistry.

[29]  A. Lonardo,et al.  Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. , 2004, Gastroenterology.

[30]  Marcelo Fiszman,et al.  Identifying Risk Factors for Metabolic Syndrome in Biomedical Text , 2007, AMIA.

[31]  T. Hassanein,et al.  The practical management of treatment failure in chronic hepatitis C: a summary of current research and management options for refractory patients. , 2007, Gastroenterology & hepatology.