Insulin resistance in chronic hepatitis C: Mechanisms and clinical relevance

Swiss Medical Weekly

Volumn 139, Issue 47-48, 2009, Pages 678-684

  Bernsmeier, Christine ^a   Heim, Markus H ^a  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

Diabetes; Hepatitis C virus; Insulin resistance; Pathophysiology; Steatosis

Indexed keywords

C PEPTIDE; GLITAZONE DERIVATIVE; GLYCOGEN SYNTHASE KINASE 3BETA; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; INTERLEUKIN 6; METFORMIN; OLMESARTAN; PEGINTERFERON ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHOPROTEIN PHOSPHATASE 2; PIOGLITAZONE; PROTEIN KINASE B; RIBAVIRIN; STEROL REGULATORY ELEMENT BINDING PROTEIN 1C; TELMISARTAN; TUMOR NECROSIS FACTOR ALPHA; VERY LOW DENSITY LIPOPROTEIN; VIRUS PROTEIN;

ADD ON THERAPY; ANTIVIRAL THERAPY; CANCER RISK; DIABETIC PATIENT; DIABETOGENESIS; DISEASE ASSOCIATION; GENOTYPE; HEPATITIS C; HEPATITIS C VIRUS; HUMAN; INSULIN BLOOD LEVEL; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIFESTYLE MODIFICATION; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; MOLECULAR MECHANICS; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; PATHOPHYSIOLOGY; PREVALENCE; PROTEIN PHOSPHORYLATION; REVIEW; RISK FACTOR; SIGNAL TRANSDUCTION; TREATMENT OUTCOME; TREATMENT RESPONSE; UPREGULATION; WEIGHT REDUCTION;

EID: 73449120393     PISSN: 14247860     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (68)

1. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13:2436-41.
2. Gumber SC, Chopra S. Hepatitis C: a multifaceted disease. Review of extrahepatic manifestations. Ann Intern Med. 1995; 123:615-20.
3. Thomas DL, Seeff LB. Natural history of hepatitis C. Clin Liver Dis. 2005;9:383-98, vi.
4. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology. 2004;127:1372-80.
5. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355:2444-51.
6. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002; 347:975-82.
7. Kamal SM, Nasser IA. Hepatitis C genotype 4: What we know and what we don't yet know. Hepatology. 2008;47:1371-83.
8. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-65.
9. Prentki M, Nolan CJ. Islet beta cell failure in type 2 diabetes. J Clin Invest 2006;116:1802-12.
10. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome - a new worldwide definition. Lancet. 2005;366:1059-62.
11. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology. 2005;42:987-1000.
12. Kahn CR. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism. 1978; 27:1893-902.
13. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-9.
14. Hui JM, Sud A, Farrell GC, Bandara P, Byth K, Kench JG, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression [corrected]. Gastroenterology. 2003;125:1695-704.
15. Bugianesi E, Marchesini G, Gentilcore E, Cua IH, Vanni E, Rizzetto M, et al. Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis. Hepatology. 2006;44:1648-55.
16. Moucari R, Asselah T, Cazals-Hatem D, Voitot H, Boyer N, Ripault MP, et al. Insulin resistance in chronic hepatitis C: association with genotypes 1 and 4, serum HCV RNA level, and liver fibrosis. Gastroenterology. 2008;134:416-23.
17. Romero-Gomez M, Del Mar Viloria M, Andrade RJ, Salmeron J, Diago M, Fernandez-Rodriguez CM, et al. Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients. Gastroenterology. 2005;128: 636-41.
18. Romero-Gomez M, Fernandez-Rodriguez CM, Andrade RJ, Diago M, Alonso S, Planas R, et al. Effect of sustained virological response to treatment on the incidence of abnormal glucose values in chronic hepatitis C. J Hepatol. 2008;48:721-7.
19. Lecube A, Hernandez C, Simo R, Esteban JI, Genesca J. Glucose abnormalities are an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. Am J Gastroenterol. 2007;102:2189-95.
20. Poustchi H, Negro F, Hui J, Cua IH, Brandt LR, Kench JG, et al. Insulin resistance and response to therapy in patients infected with chronic hepatitis C virus genotypes 2 and 3. J Hepatol. 2008;48:28-34.
21. Nasta P, Gatti F, Puoti M, Cologni G, Bergamaschi V, Borghi F, et al. Insulin resistance impairs rapid virologic response in HIV/hepatitis C virus coinfected patients on peginterferonalfa-2a. Aids. 2008;22:857-61.
22. Allison ME, Wreghitt T, Palmer CR, Alexander GJ. Evidence for a link between hepatitis C virus infection and diabetes mellitus in a cirrhotic population. J Hepatol. 1994;21:1135-9.
23. Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, et al. Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology. 1999;29:32-3.
24. Caronia S, Taylor K, Pagliaro L, Carr C, Palazzo U, Petrik J, et al. Further evidence for an association between non-insulindependent diabetes mellitus and chronic hepatitis C virus infection. Hepatology. 1999;30:1059-63.
25. Zein NN, Abdulkarim AS, Wiesner RH, Egan KS, Persing DH. Prevalence of |diabetes mellitus in patients with endstage liver cirrhosis due to hepatitis C, alcohol, or cholestatic disease. J Hepatol. 2000;32:209-17.
26. Zein CO, Levy C, Basu A, Zein NN. Chronic hepatitis C and type II diabetes mellitus: a prospective cross-sectional study. Am J Gastroenterol. 2005;100:48-55.
27. Mehta SH, Brancati FL, Strathdee SA, Pankow JS, Netski D, Coresh J, et al. Hepatitis C virus infection and incident type 2 diabetes. Hepatology. 2003;38:50-6.
28. Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000;133:592-9.
29. Shaheen M, Echeverry D, Oblad MG, Montoya MI, Teklehaimanot S, Akhtar AJ. Hepatitis C, metabolic syndrome, and inflammatory markers: results from the Third National Health and Nutrition Examination Survey [NHANES III]. Diabetes Res Clin Pract. 2007;75:320-6.
30. Harrison SA. Correlation between insulin resistance and hepatitis C viral load. Hepatology. 2006;43:1168; author reply 1168-9.
31. Veldt BJ, Chen W, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, et al. Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes mellitus. Hepatology. 2008;47:1856-62.
32. Kawaguchi Y, Mizuta T, Oza N, Takahashi H, Ario K, Yoshimura T, et al. Eradication of hepatitis C virus by interferon improves whole-body insulin resistance and hyperinsulin - aemia in patients with chronic hepatitis C. Liver Int 2009.
33. Dai CY, Huang JF, Hsieh MY, Hou NJ, Lin ZY, Chen SC, et al. Insulin resistance predicts response to peginterferonalpha/ ribavirin combination therapy in chronic hepatitis C patients. J Hepatol. 2009;50:712-8.
34. Aytug S, Reich D, Sapiro LE, Bernstein D, Begum N. Impaired IRS-1/PI3-kinase signaling in patients with HCV: a mechanism for increased prevalence of type 2 diabetes. Hepatology. 2003;38:1384-92.
35. Bernsmeier C, Duong FH, Christen V, Pugnale P, Negro F, Terracciano L, et al. Virus-induced over-expression of protein phosphatase 2A inhibits insulin signalling in chronic hepatitis C. J Hepatol. 2008;49:429-40.
36. Duong FH, Filipowicz M, Tripodi M, La Monica N, Heim MH. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology. 2004;126:263-77.
37. Christen V, Treves S, Duong FH, Heim MH. Activation of endoplasmic reticulum stress response by hepatitis viruses upregulates protein phosphatase 2A. Hepatology. 2007;46: 558-65.
38. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1:15-25.
39. Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, et al. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol. 2003;2:28.
40. Carling D. AMP-activated protein kinase: balancing the scales. Biochimie. 2005;87:87-91.
41. Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310:1642-6.
42. Kawaguchi T, Nagao Y, Tanaka K, Ide T, Harada M, Kumashiro R, et al. Causal relationship between hepatitis C virus core and the development of type 2 diabetes mellitus in a hepatitis C virus hyperendemic area: a pilot study. Int J Mol Med. 2005;16:109-14.
43. Pazienza V, Clement S, Pugnale P, Conzelman S, Foti M, Mangia A, et al. The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype-specific mechanisms. Hepatology. 2007;45:1164-71.
44. Cua IH, Hui JM, Bandara P, Kench JG, Farrell GC, Mc-Caughan GW, et al. Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines. Hepatology. 2007;46:66-73.
45. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes. 2002;51:3391-9.
46. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes. 2003;52:2784-9.
47. Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Tsukamoto K, Kimura S, et al. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance. Gastroenterology. 2004;126:840-8.
48. Gupta D, Varma S, Khandelwal RL. Long-term effects of tumor necrosis factor-alpha treatment on insulin signaling pathway in HepG2 cells and HepG2 cells overexpressing constitutively active Akt/PKB. J Cell Biochem. 2007;100:593-607.
49. Gupta D, Khandelwal RL. Modulation of insulin effects on phosphorylation of protein kinase B and glycogen synthesis by tumor necrosis factor-alpha in HepG2 cells. Biochim Biophys Acta. 2004;1671:51-8.
50. Hung CH, Lee CM, Chen CH, Hu TH, Jiang SR, Wang JH, et al. Association of inflammatory and anti-inflammatory cytokines with insulin resistance in chronic hepatitis C. Liver Int 2009.
51. Rubbia-Brandt L, Quadri R, Abid K, Giostra E, Male PJ, Mentha G, et al. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3. J Hepatol. 2000;33:106-15.
52. Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, et al. Relationship between steatosis, inflammation, and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data. Gastroenterology. 2006;130:1636-42.
53. Fartoux L, Poujol-Robert A, Guechot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut. 2005;54:1003-8.
54. Bochud P-Y, Overbeck K, Bochud M, Rickenbach M, Dufour JF, Muellhaupt B, et al. Genotype 3 is associated with rapid histological progression in chronic HCV infection. Swiss Med Wkly. 2009;139:35 S, P137.
55. Westin J, Lagging M, Dhillon AP, Norkrans G, Romero AI, Pawlotsky JM, et al. Impact of hepatic steatosis on viral kinetics and treatment outcome during antiviral treatment of chronic HCV infection. J Viral Hepat. 2007;14:29-35.
56. Lerat H, Honda M, Beard MR, Loesch K, Sun J, Yang Y, et al. Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus. Gastroenterology. 2002;122:352-65.
57. Alonzi T, Agrati C, Costabile B, Cicchini C, Amicone L, Cavallari C, et al. Steatosis and intrahepatic lymphocyte recruitment in hepatitis C virus transgenic mice. J Gen Virol. 2004; 85:1509-20.
58. Moriya K, Yotsuyanagi H, Shintani Y, Fujie H, Ishibashi K, Matsuura Y, et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol. 1997;78(Pt 7): 1527-31.
59. Perlemuter G, Sabile A, Letteron P, Vona G, Topilco A, Chretien Y, et al. Hepatitis C virus core protein inhibits microsomal triglyceride transfer protein activity and very low density lipoprotein secretion: a model of viral-related steatosis. Faseb J. 2002;16:185-94.
60. Miyamoto H, Moriishi K, Moriya K, Murata S, Tanaka K, Suzuki T, et al. Involvement of the PA28gamma-dependent pathway in insulin resistance induced by hepatitis C virus core protein. J Virol. 2007;81:1727-35.
61. Su AI, Pezacki JP, Wodicka L, Brideau AD, Supekova L, Thimme R, et al. Genomic analysis of the host response to hepatitis C virus infection. Proc Natl Acad Sci USA 2002; 99:15669-74.
62. Hickman IJ, Clouston AD, Macdonald GA, Purdie DM, Prins JB, Ash S, et al. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C. Gut. 2002;51:89-94.
63. Overbeck K, Genne D, Golay A, Negro F. Pioglitazone in chronic hepatitis C not responding to pegylated interferonalpha and ribavirin. J Hepatol. 2008;49:295-8.
64. Elgouhari HM, Cesario KB, Lopez R, Zein NN. Pioglitazone improves early virologic kinetic response to PEG IFN/RBV combination therapy in hepatitis C genotype 1 naïve patients. Hepatology. 2008;48:p. 383A.
65. Conjeevaram H, Burant CF, McKenna B. A randomized, double-blind, placebo-controlled study of PPAR-gamma agonist pioglitazone given in combination with peginterferon and riba - virin in patients with genotype-1 chronic hepatitis C. Hepatology. 2008;48:p. 384A.
66. Negro F. Peroxisome proliferator-activated receptors and hepatitis C virus-induced insulin resistance. PPAR Res. 2009;2009:483485.
67. Serfaty L, Fartoux L, Poupon R. Pioglitazone as adjuvant therapy in chronic hepatitis C: sequential rather than concomitant administration with pegylated interferon and ribavirin? J Hepatol. 2009;50:1269-71.
68. Enjoji M, Kotoh K, Kato M, Higuchi N, Kohjima M, Nakashima M, et al. Therapeutic effect of ARBs on insulin resistance and liver injury in patients with NAFLD and chronic hepatitis C: a pilot study. Int J Mol Med. 2008;22:521-7.