Background: Hypoadiponectinemia and hyperleptinemia, and reductions in the ratio of adiponectin to leptin (A/L ratio) are associated with the development of hepatic necroinflammation in nonalcoholic fatty liver, but the association of the adipokines with hepatic steatosis in chronic viral hepatitis is unclear.
Objective: To investigate the relationship between serum A/L ratio, insulin resistance, degree of hepatic steatosis, and necroinflammation in patients with chronic viral hepatitis.
Methods: We measured serum adiponectin, leptin, and resistin levels, insulin resistance, and analyzed the association between liver histopathology and the level of the adipokines in 44 patients with chronic viral hepatitis before they started treatment.
Results: We found that insulin resistance, leptin, and resistin levels tended to increase in the group with a greater degree of hepatic steatosis and necroinflammation, but that the increase was not significant. The adiponectin/leptin ratio (A/L ratio) in a group with a low degree of hepatic steatosis was significantly higher than it was in the group with a high degree of hepatic steatosis (3.1 ± 3.1 vs 1.2 ± 0.8; P = 0.008). The A/L ratio in a group with low histological activity index (HAI) scores was significantly higher than in the group with high HAI scores (3.7 ± 3.4 vs 1.1 ± 1.1; P = 0.006). Abdominal obesity was the only variable that showed a significant association with the HAI score (P = 0.03).
Conclusion: The serum A/L ratio in patients with chronic viral hepatitis showed a significant inverse association with their degree of hepatic steatosis and necroinflammation.
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1. Sanyal AJ. Review article: non-alcoholic fatty liver disease and hepatitis C-risk factors and clinical implications. Aliment Pharmacol Ther. 2005; 22(Suppl 2):48-51.
2. Marra F Aleffi S Bertolani C Petrai I Vizzutti F. Review article: the pathogenesis of fibrosis in nonalcoholic steatohepatitis. Aliment Pharmacol Ther. 2005; 22(Suppl 2):44-7.
3. Trombetta M Spiazzi G Zoppini G Muggeo M. Review article: type 2 diabetes and chronic liver disease in the Verona diabetes study. Aliment Pharmacol Ther. 2005; 22(Suppl 2):24-7.
4. Lonardo A Adinolfi LE Loria P Carulli N Ruggiero G Day CP. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology. 2004; 126:586-97.
5. Clouston AD Jonsson JR Powell EE. Steatosis as a cofactor in other liver diseases: hepatitis C virus alcohol hemochromatosis and others. Clin Liver Dis. 2007; 11:173-89.
6. Yokoyama H Hirose H Ohgo H Saito I. Inverse association between serum adiponectin level and transaminase activities in Japanese male workers. J Hepatol. 2004; 41:19-24.
7. Antunez I Aponte N Fernandez-Carbia A Rodriguez-Perez F Toro DH. Steatosis as a predictive factor for treatment response in patients with chronic hepatitis C. P R Health Sci J. 2004; 23:57-60.
8. Myers RP Messous D Poynard T Imbert-Bismut F. Association between leptin metabolic factors and liver histology in patients with chronic hepatitis C. Can J Gastroenterol. 2007; 21:289-94.
9. Brunt EM Janney CG Di Bisceglie AM Neuschwander-Tetri BA Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999; 94:2467-74.
10. Hu KQ Kyulo NL Esrailian E Thompson K Chase R Hillebrand DJ Runyon BA. Overweight and obesity hepatic steatosis and progression of chronic hepatitis C: a retrospective study on a large cohort of patients in the United States. J Hepatol. 2004; 40:147-54.
11. Adinolfi LE Durante-Mangoni E Zampino R Ruggiero G. Review article: hepatitis C virus-associated steatosis-pathogenic mechanisms and clinical implications. Aliment Pharmacol Ther. 2005; 22(Suppl 2):52-5.
12. Harrison SA. Steatosis and chronic hepatitis C infection: mechanisms and significance. Clin Gastroenterol Hepatol. 2005; 3:S92-6.
13. Guidi M Muratori P Granito A Muratori L Lenzi M Bianchi FB. Steatosis in chronic hepatitis C. Gut. 2006; 55:1047-8.
14. Matos CA Perez RM Pacheco MS Figueiredo-Mendes CG Lopes-Neto E Oliveira EB et al. Steatosis in chronic hepatitis C: relationship to the virus and host risk factors. J Gastroenterol Hepatol. 2006; 21:1236-9.
15. Asselah T Rubbia-Brandt L Marcellin P Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut. 2006; 55:123-30.
16. Szanto P Grigorescu M Dumitru I Serban A. Steatosis in hepatitis C virus infection. Response to anti-viral therapy. J Gastrointestin Liver Dis. 2006; 15:117-24.
17. Zein NN Poterucha JJ. Steatosis in hepatitis C: the missing link to metabolic abnormalities? Am J Gastroenterol. 2006; 101:2616-8.
18. Asselah T Boyer N Guimont MC Cazals-Hatem D Tubach F Nahon K et al. Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C. Gut. 2003; 52:1638-43.
19. Testino G Sumberaz A. Liver steatosis and antiviral therapy in chronic hepatitis C. Liver Int. 2007; 27:287.
20. Sanyal AJ Contos MJ Sterling RK Luketic VA Shiffman ML Stravitz RT et al. Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Am J Gastroenterol. 2003; 98:2064-71.
21. Gordon A McLean CA Pedersen JS Bailey MJ Roberts SK. Hepatic steatosis in chronic hepatitis B and C: predictors distribution and effect on fibrosis. J Hepatol. 2005; 43:38-44.
22. Romero-Gomez M. Hepatitis C and insulin resistance: steatosis fibrosis and non-response. Rev Esp Enferm Dig. 2006; 98:605-15.
23. Ramesh S Sanyal AJ. Hepatitis C and nonalcoholic fatty liver disease. Semin Liver Dis. 2004; 24:399-413.
24. Bjornsson E Angulo P. Hepatitis C and steatosis. Arch Med Res. 2007; 38:621-7.
25. Lonardo A Loria P Adinolfi LE Carulli N Ruggiero G. Hepatitis C and steatosis: a reappraisal. J Viral Hepat. 2006; 13:73-80.
26. Koike K. Hepatitis C as a metabolic disease: Implication for the pathogenesis of NASH. Hepatol Res. 2005; 33:145-50.
27. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. JHepatol. 2007; 47:598-607.
28. Durante-Mangoni E Zampino R Marrone A Tripodi MF Rinaldi L Restivo L et al. Hepatic steatosis and insulin resistance are associated with serum imbalance of adiponectin/tumour necrosis factor-á in chronic hepatitis C patients. Aliment Pharmacol Ther. 2006; 24:1349-57.
29. Hu KQ Currie SL Shen H Cheung RC Ho SB Bini EJ et al. Clinical implications of hepatic steatosis in patients with chronic hepatitis C: a multicenter study of U.S. veterans. Dig Dis Sci. 2007; 52:570-8.
30. Sayed HA El Ayyat A El Dusoki H Zoheiry M Mohamed S Hassan M et al. A cross sectional study of hepatitis B C some trace elements heavy metals aflatoxin B1 and schistosomiasis in a rural population Egypt. J Egypt Public Health Assoc. 2005; 80:355-88.
31. Bedossa P Moucari R Chelbi E Asselah T Paradis V Vidaud M et al. Evidence for a role of nonalcoholic steatohepatitis in hepatitis C: a prospective study. Hepatology. 2007; 46:380-7.
32. Oben JA Paulon E. Fatty liver in chronic hepatitis C infection: unravelling the mechanisms. Gut. 2007; 56:1186-8.
33. Anty R Gelsi E Giudicelli J Marine-Barjoan E Gual P Benzaken S et al. Glucose intolerance and hypoadiponectinemia are already present in lean patients with chronic hepatitis C infected with genotype non-3 viruses. Eur J Gastroenterol Hepatol. 2007; 19:671-7.