Research Communication | Open Access
Huseyin Ataseven, Ibrahim Halil Bahcecioglu, Nalan Kuzu, Mehmet Yalniz, Selman Celebi, Ahmet Erensoy, Bilal Ustundag, "The Levels of Ghrelin, Leptin, TNF-, and IL-6 in Liver Cirrhosis and Hepatocellular Carcinoma due to HBV and HDV Infection", Mediators of Inflammation, vol. 2006, Article ID 078380, 6 pages, 2006. https://doi.org/10.1155/MI/2006/78380
The Levels of Ghrelin, Leptin, TNF-, and IL-6 in Liver Cirrhosis and Hepatocellular Carcinoma due to HBV and HDV Infection
Background/Aim. Malnutrition, a common problem in liver cirrhosis and HCC, may readily deteriorate the clinical functions with resultant poor prognosis. Beside the hyper catabolic state frequently encountered in chronic liver disease and HCC, anorexia and reduced food intake also worsen the malnutrition. The recently discovered peptide hormone ghrelin acts as a counterpart of leptin in regulation of food intake and fat utilization. The aim of the present study was to investigate the ghrelin and leptin levels in cirrhosis and HCC due to hepatitis B and D viruses, and the association of ghrelin and leptin with TNF-, IL-6 and the severity of the disease. Materials and methods. We measured serum ghrelin, leptin, TNF-, and IL-6 levels using specific immunoassay in 45 patients (23 cirrhosis, 22 HCC) with HBV and/or HDV and in 25 control subjects. Results. In comparison to controls, serum ghrelin, TNF-, and IL-6 levels were significantly higher in cirrhosis and HCC (), whereas serum leptin levels were found decreased (). There was a positive correlation between ghrelin and TNF-, and a negative correlation between leptin and TNF- (). Conclusion. In cirrhosis and HCC due to HBV or HDV, serum ghrelin levels were increased with a corresponding decrease in serum leptin concentrations, acting as a physiological counterpart of ghrelin. The increasing of ghrelin is more prominent in Child C cirrhosis and the level was correlated with TNF-. The presence of nutritional and metabolic abnormalities, including malnutrition, in cirrhosis and HCC may, at least partly, elucidate high ghrelin and low leptin levels.
- G Montalto, M Cervello, L Giannitrapani, F Dantona, A Terranova, and L A Castagnetta, “Epidemiology, risk factors, and natural history of hepatocellular carcinoma,” Annals of the New York Academy of Sciences, vol. 963, pp. 13–20, 2002.
- D M Parkin, F Bray, J Ferlay, and P Pisani, “Estimating the world cancer burden: Globocan 2000,” International Journal of Cancer, vol. 94, no. 2, pp. 153–156, 2001.
- F W Guglielmi, C Panella, A Buda et al., “Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the “Nutritional Problems in Gastroenterology” Section of the Italian Society of Gastroenterology (SIGE),” Digestive and Liver Disease, vol. 37, no. 9, pp. 681–688, 2005.
- T. Schütz, A-E. Roske, A-C. Lehmann, H. Lochs, and M. Plauth, “Pathogenesis of malnutrition in patients with hepatocellular carcinoma (HCC),” Clinical Nutrition, vol. 17, no. suppl 1, pp. 12–13, 1998.
- M Merli, O Riggio, and L Dally, “Does malnutrition affect survival in cirrhosis? (Policentrica Italiana Nutrizione Cirrosi),” Hepatology, vol. 23, no. 5, pp. 1041–1046, 1996.
- O Riggio, S Angeloni, L Ciuffa et al., “Malnutrition is not related to alterations in energy balance in patients with stable liver cirrhosis,” Clinical Nutrition, vol. 22, no. 6, pp. 553–559, 2003.
- “Italian Multicentre Cooperative Project on Nutrition in Liver Cirrhosis. Nutritional status in cirrhosis,” Journal of Hepatology, vol. 21, no. 3, pp. 317–325, 1994.
- C L Rock, A M Coulstan, and M T Ruffin, “Diet therapy,” in Harrison's Principles of Internal Medicine, A S Fauci, E Braunwald, and K J Isselbacher, Eds., pp. 465–472, McGraw-Hil, New York, NY, 14th edition, 1998.
- M Kojima, H Hosoda, Y Date, M Nakazato, H Matsuo, and K Kangawa, “Ghrelin is a growth- hormone-releasing acylated peptide from stomach,” Nature, vol. 402, no. 6762, pp. 656–660, 1999.
- M Nakazato, N Murakami, Y Date et al., “A role for ghrelin in the central regulation of feeding,” Nature, vol. 409, no. 6817, pp. 194–198, 2001.
- M Shintani, Y Ogawa, K Ebihara et al., “Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway,” Diabetes, vol. 50, no. 2, pp. 227–232, 2001.
- M Tschop, D L Smiley, and M L Heiman, “Ghrelin induces adiposity in rodents,” Nature, vol. 407, no. 6806, pp. 908–913, 2000.
- A M Wren, C J Small, H L Ward et al., “The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion,” Endocrinology, vol. 141, no. 11, pp. 4325–4328, 2000.
- J M Friedman and J L Halas, “Leptin and the regulation of body weight in mammals,” Nature, vol. 395, no. 6704, pp. 763–770, 1998.
- J F Caro, M K Sinha, J W Kolaczynski, P L Zhang, and R V Considine, “Leptin: the tale of an obesity gene,” Diabetes, vol. 45, no. 11, pp. 1455–1462, 1996.
- J M Friedman, “Leptin, leptin receptors and the control of body weight,” European Journal of Medical Research, vol. 2, no. 1, pp. 7–13, 1997.
- A Kennedy, T W Gettys, P Watson et al., “The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure,” Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 4, pp. 1293–1300, 1997.
- S G Bouret, S J Draper, and R B Simerly, “Formation of projection pathways from the arcuate nucleus of the hypothalamus to hypothalamic regions implicated in the neural control of feeding behavior in mice,” Journal of Neuroscience, vol. 24, no. 11, pp. 2797–2805, 2004.
- R S Ahima and S Y Osei, “Leptin signaling,” Physiology & Behavior, vol. 81, no. 2, pp. 223–241, 2004.
- R Faggioni, K R Feingold, and C Grunfeld, “Leptin regulation of the immune response and the immunodeficiency of malnutrition,” FASEB Journal, vol. 15, no. 14, pp. 2565–2571, 2001.
- S Aleffi, I Petrai, C Bertolani et al., “Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells,” Hepatology, vol. 42, no. 6, pp. 1339–1348, 2005.
- J Dötsch, K Nüsken, M Schroth, W Rascher, and U Meißner, “Alterations of leptin and ghrelin serum concentrations in renal disease: simple epiphenomena?,” Pediatric Nephrology, vol. 20, no. 6, pp. 701–706, 2005.
- B Beutler and A Cerami, “Cachectin (tumor necrosis factor): a macrophage hormone governing cellular metabolism and inflammatory response,” Endocrine Reviews, vol. 9, no. 1, pp. 57–66, 1988.
- K J Tracey and A Cerami, “Tumor necrosis factor: a pleiotropic cytokine and therapeutic target,” Annual Review of Medicine, vol. 45, pp. 491–503, 1994.
- S-S Wang, F-Y Lee, C-C Chan et al., “Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection,” Clinical Science, vol. 98, no. 4, pp. 419–425, 2000.
- M Odeh, E Sabo, I Srugo et al., “Serum levels of tumor necrosis factor-alpha correlate with severity of hepatic encephalopathy due to chronic liver failure,” Liver International, vol. 24, no. 2, pp. 110–116, 2004.
- J Le and J Vilcek, “Interleukin 6: a multifunctional cytokine regulating immune reactions and the acute phase protein response,” Laboratory Investigation, vol. 61, no. 6, pp. 588–602, 1989.
- J Deviere, J Content, C Denys et al., “High interleukin-6 serum levels and increased production by leucocytes in alcoholic liver cirrhosis. Correlation with IgA serum levels and lymphokines production,” Clinical and Experimental Immunology, vol. 77, no. 2, pp. 221–225, 1989.
- C Gerstner, T Schuetz, V Von Baehr et al., “Correlation between energy expenditure, nutrient intake, malnutrition and activation of the inflammatory system in patients with hepatic cirrhosis,” Journal of Hepatology, vol. 34, no. suppl 1, pp. 195–196, 2001.
- K Onodera, A Kato, and K Suzuki, “Serum leptin concentrations in liver cirrhosis: relationship to the severity of liver dysfunction and their characteristic diurnal profiles,” Hepatology Research, vol. 21, no. 3, pp. 205–212, 2001.
- A Di Lelio, C Cestari, A Lomazzi, and L Beretta, “Cirrhosis: diagnosis with sonographic study of the liver surface,” Radiology, vol. 172, no. 2, pp. 389–392, 1989.
- M Bruix, J M Sherman, J M Llovet et al., “Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver,” Journal of Hepatology, vol. 35, no. 3, pp. 421–430, 2001.
- M K Tü̈rkdoğan, H Bozkurt, I Uygan et al., “Chronic hepatitis delta virus infection in Van region of eastern Turkey,” The Turkish Journal of Gastroenterology, vol. 16, no. 1, pp. 17–20, 2005.
- P Groshiede and P Van Damme, “Epidemiology of hepatitis B infection, prevention and control of hepatitis B in the comunity,” in Communicable Disease Series. No: 1, J Hallauer, J Jane, E McCloy, A Merheus, and C Roure, Eds., pp. 17–26, World Health Organization, European Organization Office, Geneva, Switzerland, 1996.
- Ö Uzunalimoglu, C Yurdaydin, H Cetinkaya et al., “Risk factors for hepatocellular carcinoma in Turkey,” Digestive Diseases and Sciences, vol. 46, no. 5, pp. 1022–1028, 2001.
- M Tajika, M Kato, H Mohri et al., “Prognostic value of energy metabolism in patients with viral liver cirrhosis,” Nutrition, vol. 18, no. 3, pp. 229–234, 2002.
- F Tacke, G Brabant, E Kruck et al., “Ghrelin in chronic liver disease,” Journal of Hepatology, vol. 38, no. 4, pp. 447–454, 2003.
- F F Casanueva and C Dieguez, “Ghrelin a new hormone implicated in the regulation of growth hormone secretion and body energy homeostasis,” Growth, Genetics & Hormones, vol. 20, no. 1, pp. 1–8, 2004.
- J Ockenga, S C Bischoff, H L Tillmann et al., “Elevated bound leptin correlates with energy expenditure in cirrhotics,” Gastroenterology, vol. 119, no. 6, pp. 1656–1662, 2000.
- A J McCullough, E Bugianesi, G Marchesini, and S C Kalhan, “Gender-dependent alterations in serum leptin in alcoholic cirrhosis,” Gastroenterology, vol. 115, no. 4, pp. 947–953, 1998.
- F F Bolukbas, C Bolukbas, M Horoz et al., “Child-Pugh classification dependent alterations in serum leptin levels among cirrhotic patients: a case controlled study,” BMC Gastroenterology, vol. 4, no. 1, p. 23, 2004.
- R Testa, R Franceschini, E Giannini et al., “Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis,” Journal of Hepatology, vol. 33, no. 1, pp. 33–37, 2000.
- S Y Lin, Y Y Wang, and W H Sheu, “Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis,” Clinical Endocrinology, vol. 57, no. 6, pp. 805–811, 2002.
- A V Greco, G Mingrone, A Favuzzi et al., “Serum leptin levels in post-hepatitis liver cirrhosis,” Journal of Hepatology, vol. 33, no. 1, pp. 38–42, 2000.
- A Comlekci, H Akpinar, S Yesil et al., “Serum leptin levels in patients with liver cirrhosis and chronic viral hepatitis,” Scandinavian Journal of Gastroenterology, vol. 38, no. 7, pp. 779–786, 2003.
- D G Wahl, J-M Dollet, M Kreher, B Champigneulle, M-A Bigard, and P Gaucher, “Relationship of insulin resistance to protein-energy malnutrition in patients with alcoholic liver cirrhosis: effect of short-term nutritional support,” Alcoholism: Clinical and Experimental Research, vol. 16, no. 5, pp. 971–978, 1992.
- S Y Kwon, S S Kim, O S Kwon et al., “Prognostic significance of glycaemic control in patients with HBV and HCV-related cirrhosis and diabetes mellitus,” Diabetic Medicine, vol. 22, no. 11, pp. 1530–1535, 2005.
- E J Williams and J P Iredale, “Liver cirrhosis,” Postgraduate Medical Journal, vol. 74, no. 870, pp. 193–202, 1998.
- H Tilg, A Wilmar, W Vogel et al., “Serum levels of cytokines in chronic liver diseases,” Gastroenterology, vol. 103, no. 1, pp. 264–274, 1992.
- A Inui, “Cancer anorexia-cachexia syndrome: are neuropeptides the key?,” Cancer Research, vol. 59, no. 18, pp. 4493–4501, 1999.
- D P Kotler, “Cachexia,” Annals of Internal Medicine, vol. 133, no. 8, pp. 622–634, 2000.
- K Toda, N Kumagai, K Tsuchimoto et al., “Induction of hepatic stellate cell proliferation by LPS-stimulated peripheral blood mononuclear cells from patients with liver cirrhosis,” Journal of Gastroenterology, vol. 35, no. 3, pp. 214–220, 2000.
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