Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis

  • Elsayed, Engy Yousry (Internal Medicine, Oncology and Clinical Pathology Departments, Faculty of Medicine, Ain Shams University) ;
  • Mosalam, Nesreen Ahmed (Internal Medicine, Oncology and Clinical Pathology Departments, Faculty of Medicine, Ain Shams University) ;
  • Mohamed, Noha Refaat (Internal Medicine, Oncology and Clinical Pathology Departments, Faculty of Medicine, Ain Shams University)
  • Published : 2015.11.04


Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer related death overall. The role of insulin resistance in the development of HCC associated with chronic HCV infection has not been established. Resistin is a polypeptide hormone belonging to the adipokine family which could contribute to tumorigenesis and angiogenesis. Our aim was to study serum resistin and insulin resistance as risk factors for HCC in HCV cirrhotic patients. Materials and Methods: This prospective case controlled study included 100 patients with HCV related liver cirrhosis and HCC, 100 patients with HCV related liver cirrhosis without HCC and 50 apparently healthy participants as controls. For all subjects, liver profile, serologic markers for viral hepatitis, lipid profile, alpha-fetoprotein level (AFP), homeostasis model assessment (HOMA) were examined along with resistin. Results: HCC patients had higher mean values of HOMA-IR and resistin than cirrhotic patients and the control subjects (p<0.01). HOMA and resistin were considered independent risk factors in development of HCC, those patients with resistin > 12 ng/ml and HOMA > 4 being 1.6 times more likely to have HCC. Conclusions: HOMA and serum resistin allow for early identification of patients with cirrhosiswho are at substantially increased risk of HCC. Recommendation: HOMA and serum resistin could represent novel markers to identify HCV cirrhotic patients at greater risk of development of HCC.


  1. Alexia C, Fallot G, Lasfer M, et al., (2004). An evaluation of the role of insulin-like growth factors (IGF) and of type-I IGF receptor signalling in hepatocarcinogene-sisand in the resistance of hepatocarcinoma cells against drug induced apoptosis. Bi-ochem Pharmacol, 68, 1003-15.
  2. Bota S, Piscaglia F, Bolondi L (2012). Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma. Liver cancer, 13, 190-200.
  3. Bertolani C, Sancho-Bru P, Failli P, et al (2006). Resistin as an Intrahepatic Cy-tokine: overexpression during chronic injury and induction of proinflammatory ac-tions in hepatic stellate cells. Am J Pathol, 169, 2042-2053.
  4. Cowey S, Hardy RW (2006). The Metabolic syndrome: a high risk state for can-cer? Am J Pathol, 169, 1505-22.
  5. Dailey G(2004) : New strategies for basal insulin treatment in type 2 diabetes melli-tus. Clin Ther, 26, 889-901.
  6. Dalamaga M, Sotiropoulos G, Karmaniolas K, et al., (2013). Serum resistin: a bi-omarker of breast cancer inpostmenopausal women? Association with clinicopathological characteristics, tumor markers, inflammatory and metabolic parameters. Clin Biochem, 46, 584-590.
  7. Diehl AM(2002). Nonalcoholic steatosis and steatohepatitis. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines. Am J Physiol Gastrointest Liver Physiol, 282, 1-5.
  8. Donadon V, Balbi M, Zanette G (2009). Hyperinsulinemia and risk for hepatocel-lular carcinoma in patients with chronic liver diseases and Type 2 diabetes mellitus. Expert Rev Gastroenterol Hepatol, 3, 465-7.
  9. El-Zayadi A-R, Anis M (2012). Hepatitis C virus in-duced insulin resistance impairs response to anti viral therapy. World J Gastroenterol, 18, 212-24.
  10. Eslam M, Khattab MA, Harrison SA ( 2011). Insulin resistance and hepatitis C: An evolving story. Gut, 60, 1139-51
  11. Fartoux L, Poujol-Robert A, Guechot J, et al. ( 2005). Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut, 54, 1003-8.
  12. Gomaa AA, Helmy AM, El Fayuomy KN, et al (2010). Role of insulin re-sistance in the development of hepatocellularcarcinoma in patients with chronic hepa-titis C. AAMJ, 8, 294-313.
  13. Housa D, Housova J, Vernerova Z, et al (2006). Adipocytokines and cancer. Physiol Res, 55, 233-44.
  14. Hsu WY, Chao YW, Tsai YL, et al (2011). Resistin induces monocyte-endothelial cell adhesion by increasing ICAM-1 and VCAM-1 expression in endothe-lial cells via p38MAPKdependent pathway. J Cell Physiol, 226, 2181-8. 45.
  15. Hui-Qi Qu, Quan Li, Anne R. Rentfro, et al (2011). The definition of insulin resistance using HOMA-IR for americans of mexican descent using machine learning. PLoS One, 6, 21041.
  16. Hung CH, Wang JH, Hu TH, et al (2010). Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J Gastroenterol, 16, 2265-71.
  17. Irshad M, Iqbal A, Ansari MA, et al (2013). Relation of insulin resistance (IR) with viral etiology and blood level of cytokines in patients with liver diseases. Glo Adv Res J Med Med Sci, 2, 75-83.
  18. Jansson SP, Andersson DK and Svardsudd K (2010). Mortality trends in subjects with and without diabetes during 33 years of follow-up. Diabetes Care, 33, 551-556.
  19. Kakizaki S, Sohara N, Yamazaki Y, et al (2008). Elevated plasma resistin con-centrations in patients with liver cirrhosis. J Gastroenterol Hepatol, 23, 73-7.
  20. Kawaguchi T, Taniguchi E, Itou M, et al (2011). Insulin resistance and chronic liver disease. World J Hepatol, 3, 99-107.
  21. Kawaguchi T, Taniguchi E, Morita Y, et al (2010). Association of exogenous insulin or sulphonylurea treatment with an increased incidence of hepatoma in pa-tients with hepatitis C virus infection. Liver Int, 30, 479-86.
  22. Martin Kopa, Jana Muchova, Zdenka Durac kova (2013). Modulation of insulin resistance by PUFA in metabolic tissues Eur. J Lipid Sci Technol, 115, 475-482.
  23. Mohamed AA, Loutfy SA, Craik JD, et al (2011). Chronic hepatitis C genotype-4 infection: role of insulin resistance in hepatocellular carcinoma. Virol, 8, 496.
  24. Mohamed FS, El-Bardiny M, Abdel-Moety AA. et al (2014). Assessment of in-sulin resistance, serum adiponectin and ferritin levels in HCC patients before and af-ter radiofrequency ablation. JMSCR, 2, 1065-83.
  25. Nkontchouemail G, Bastard J, Ziol M, et al (2010). Insulin resistance, serum leptin, and adiponectin levels and outcomes of viral hepatitis C cirrhosis. J Hepatol, 53, 827-33.
  26. Yagmur E, Trautwein C, Gressner AM, et al (2006). Resistin serum levels are associated with insulinresistance, disease severity, clinical complications, and prog-nosis in patients with chronic liver diseases. Am J Gastroenterol, 101, 1244-52.
  27. Yang CC, Chang SF, Chao JK, et al (2014). Activation of AMPactivated protein kinase attenuates hepatocellular carcinoma cell adhesion stimulated by adipokine resistin. BMC Cancer, 14, 112-20.

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