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DOI: 10.1055/s-2003-44291
J. A. Barth Verlag in Georg Thieme Verlag Stuttgart · New York
TIPS Implantation Raises Leptin Levels in Patients with Liver Cirrhosis
Publikationsverlauf
Received: September 26, 2002
First decision: November 24, 2002
Accepted: March 3, 2003
Publikationsdatum:
13. November 2003 (online)
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Abstract
Increased leptin levels in patients with liver cirrhosis are postulated to result in malnutrition and increased energy expenditure. Since cirrhotic patients show improved nutritional status after a transjugular intrahepatic portosystemic stent shunt (TIPS), it was the aim of this study to evaluate plasma leptin levels and their influence on nutritional status prior to and after the TIPS procedure. We evaluated plasma leptin levels, body mass index (BMI), Child-Pugh score and pertinent biochemical parameters in 31 patients (19 men and 12 women) with severe complications of liver cirrhosis (74 % ethyltoxic men, 50 % ethyltoxic in women), prior to and after TIPS. Nineteen cirrhotic patients without TIPS served as controls.
In women ascitic-free BMI significantly increased (from 22.8 ± 4.6 kg/m2 to 23.9 ± 4.9; p = 0.004 three months after TIPS), whereas in men only a tendency toward higher values (26.1 ± 4.7 vs. 26.7 ± 4.4; p = 0.28) was found. Analysis of peripheral venous leptin concentrations before and three months after TIPS revealed a significant increase in women (11.9 ± 8.8 ng/ml vs. 18.6 ± 14.9; p = 0.009) and in men (7.7 ± 6.2 ng/ml vs. 12.2 ± 9.0; p = 0.005). In addition, the leptin-BMI ratio increase significantly in women and men three months after TIPS implantation (women 0.49 ± 0.29 vs. 0.73 ± 0.52; p = 0.017; men 0.28 ± 0.22 vs. 0.43 ± 0.28; p = 0.002). On the other hand, patients without TIPS implantation showed no significant alterations of BMI and peripheral venous leptin concentrations.
After TIPS implantation in liver cirrhotic patients, leptin levels were increased and the nutritional status improved. Therefore, our analysis suggests that in patients with predominantly ethyltoxic liver cirrhosis, elevated leptin levels are not a major reason for poorer body composition.
Key words
Liver cirrhosis - TIPS - BMI - leptin - malnutrition
References
- 1 Allard J P, Chau J, Sandokji K, Blendis L M, Wong F. Effects of ascites resolution after successful TIPS on nutrition in cirrhotic patients with refractory ascites. Am J Gastroenterol. 2001; 96 2442-2447
- 2 Arpaci F, Yilmaz M I, Ozet A, Ayta H, Ozturk B, Komurcu S, Ozata M. Low serum leptin level in colon cancer patients without significant weight loss. Tumori. 2002; 88 147-149
- 3 Arroyo V, Gines P, Gerbes A L, Dudley F J, Gentilini P, Laffi G, Reynolds T B, Ring-Larsen H, Scholmerich J. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club Hepatology. 1996; 23 164-176
- 4 Auwerx J, Staels B. Leptin. Lancet. 1998; 351 737-742
- 5 Bado A, Levasseur S, Attoub S, Kermorgant S, Laigneau J P, Bortoluzzi M N, Mouzo L, Lehy T, Guerre-Millo M, Le Marchand-Brustel Y, Lewin M J. The stomach is a source of leptin. Nature. 1998; 394 790-793
- 6 Ben-Ari Z, Schafter Z, Sulkes J, Manhaim V, Tur-Kaspa R, Fainaru M. Alterations in serum leptin in cirrhotic liver disease. Dig Dic Sci. 2002; 47 183-189
- 7 Brown D R, Berkowitz D E, Breslow M J. Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer. J Clin Endocrinol Metab. 2001; 86 162-166
- 8 Campillo B, Sherman E, Richardet J P, Bories P N. Serum leptin levels in alcoholic liver cirrhosis: relationship with gender, nutritional status, liver function and energy metabolism. Eur J Clin Nutr. 2001; 55 980-988
- 9 Campfield L A, Smith F J, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science. 1995; 269 546-549
- 10 Considine R V, Sinha M K, Heiman M L, Kriauciunas A, Stephens T W, Nyce M R, Ohannesain J P, Marco C C, McKee L J, Bauer T L. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996; 334 292-295
- 11 Crespo J, Rivero M, Fabrega E, Cayon A, Amado J A, Garcia-Unzeta M T, Pons-Romero F. Plasma leptin and TNF-alpha levels in chronic hepatitis C patients and their relationship to hepatic fibrosis. Dig Dis Sci. 2002; 47 1604-1610
- 12 Fruhbeck G, Jebb S A, Prentice A M. Leptin: physiology and pathophysiology. Clin Physiol. 1998; 18 399-419
- 13 Greco A V, Mingrone G, Favuzzi A, Capristo E, Gniuli D, Addolorato G, Brunani A, Cavagnin F, Gasbarrini G. Serum leptin levels in post-hepatitis liver cirrhosis. J Hepatol. 2000; 33 38-42
- 14 Grunfeld C, Zhao C, Fuller J, Pollack A, Moser A, Friedman J, Feingold K R. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest. 1996; 97 2152-2157
- 15 Halaas J L, Gajiwala K S, Maffei M, Cohen S L, Chait B T, Rabinowitz D, Lallone R L, Burley S K, Friedman J M. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995; 269 543-546
- 16 Henriksen J H, Holst J J, Moller S, Brinch K, Bendtsen F. Increased circulating leptin in alcoholic cirrhosis: relation to release and disposal. Hepatology. 1999; 29 1818-1824
- 17 Hynes G R, Jones P J. Leptin and its role in lipid metabolism. Curr Opin Lipidol. 2001; 12 321-327
- 18 Ikejima K, Honda H, Yoshikawa M, Hirose M, Kitamura T, Takei Y, Sato N. Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology. 2001; 34 288-297
- 19 Jensen M D, Moller N, Nair K S, Eisenberg P, Landt M, Klein S. Regional leptin kinetics in humans. Am J Clin Nutr. 1999; 69 18-21
- 20 Kaplan L M. Leptin, obesity, and liver disease. Gastroenterology. 1998; 115 997-1001
- 21 Kaser S, Foger B, Waldenberger P, Nachbaur K, Propst A, Jaschke W, Vogel W, Patsch J R. Transjugular intrahepatic portosystemic shunt (TIPS) augments hyperinsulinemia in patients with cirrhosis. J Hepatol. 2000; 33 902-906
- 22 Kennedy A, Gettys T W, Watson P, Wallace P, Ganaway E, Pan Q, Garvey W T. The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure. J Clin Endocrinol Metab. 1997; 82 1293-1300
- 23 Klein S, Coppack S W, Mohamed-Ali V, Landt M. Adipose tissue leptin production and plasma leptin kinetics in humans. Diabetes. 1996; 45 984-987
- 24 Leonhardt U, Ritzel U, Schafer G, Becker W, Ramadori G. Serum leptin levels in hypo- and hyperthyroidism. J Endocrinol. 1998; 157 75-79
- 25 Licinio J, Negrao A B, Mantzoros C, Kaklamani V, Wong M L, Bongiorno P B, Negro P P, Mulla A, Veldhuis J D, Cearnal L, Flier J S, Gold P W. Sex differences in circulating human leptin pulse amplitude: clinical implications. J Clin Endocrinol Metab. 1998; 83 4140-4147
- 26 Mantovani G, Maccio A, Madeddu C, Mura L, Massa E, Mudu M C, Mulas C, Lusso M R, Gramignano G, Piras M B. Serum values of proinflammatory cytokines are inversely correlated with serum leptin levels in patients with advanced stage cancer at different sites. J Mol Med. 2001; 79 406-414
- 27 Mantzoros C S. The role of leptin in human obesity and disease: a review of current evidence. Ann Intern Med. 1999; 130 671-680
- 28 McCullough A J, Bugianesi E, Marchesini G, Kalhan S C. Gender-dependent alterations in serum leptin in alcoholic cirrhosis. Gastroenterology. 1998; 115 947-953
- 29 Merabet E, Dagogo-Jack S, Coyne D W, Klein S, Santiago J V, Hmiel S P, Landt M. Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol Metab. 1997; 82 847-850
- 30 Meyer C, Robson D, Rackovsky N, Nadkarni V, Gerich J. Role of the kidney in human leptin metabolism. Am J Physiol. 1997; 273 E903-E907
- 31 Mix H, Widjaja A, Jandl O, Cornberg M, Kaul A, Goke M, Beil W, Kuske M, Brabant G, Manns M P, Wagner S. Expression of leptin and leptin receptor isoforms in the human stomach. Gut. 2000; 47 481-486
- 32 Moses A G, Dowidar N, Holloway B, Waddell I, Fearon K C, Ross J A. Leptin and its relation to weight loss, ob gene expression and the acute-phase response in surgical patients. Br J Surg. 2001; 88 588-593
- 33 Nakamuta M, Tada S, Uchimura K, Enjoji M, Kinukawa N, Iwamoto H, Sugimoto R, Shimada M, Ohashi M, Sugimachi K, Nawata H. Serum leptin levels in patients with nonalcoholic chronic liver disease. Hepatogastroenterology. 2001; 48 527-532
- 34 Nicolas J M, Fernandez-Sola J, Fatjo F, Casamitjana R, Bataller R, Sacanella E, Tobias E, Badia E, Estruch R. Increased circulating leptin levels in chronic alcoholism. Alcohol Clin Exp Res. 2001; 25 83-88
- 35 Nolte W, Munke H, Schindler C G, Figulla H R, Werner G, Leonhardt U, Hartmann H, Ramadori G. Doppler sonographic short- and long-term studies of portal hemodynamics following transjugular intrahepatic portosystemic shunt (TIPSS). Z Gastroenterol. 1998; 36 491-499
- 36 Nolte W, Wiltfang J, Schindler C, Munke H, Unterberg K, Zumhasch U, Figulla H R, Werner G, Hartmann H, Ramadori G. Portosystemic hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with cirrhosis: clinical, laboratory, psychometric, and electroencephalographic investigations. Hepatology. 1998; 28 1215-1225
- 37 Ockenga J, Bischoff S C, Tillmann H L, Rifai K, Widjaja A, Böker K HW, Manns M P, Brabant G. Elevated bound leptin correlates with energy expenditure in cirrhotics. Gastroenterology. 2000; 119 1656-1662
- 38 Odamaki M, Furuya R, Yoneyama T, Nishikino M, Hibi I, Miyaji K, Kumagai H. Association of the serum leptin concentration with weight loss in chronic hemodialysis patients. Am J Kidney Dis. 1999; 33 361-368
- 39 Onodera K, Kato A, Suzuki K. Serum leptin concentrations in liver cirrhosis: relationship to the severity of liver dysfunction and their characteristic diurnal profiles. Hepatol Res. 2001; 21 205-212
- 40 Piche T, Gelsi E, Schneider S M, Hebuterne X, Giudicelli J, Ferrua B, Laffont C, Benzaken S, Hastier P, Montoya M L, Longo F, Rampal P, Tran A. Fatigue is associated with high circulating leptin levels in chronic hepatitis C. Gut. 2002; 51 434-439
- 41 Potter J J, Womack L, Mezey E, Anania F A. Transdifferentiation of rat hepatic stellate cells results in leptin expression. Biochem Biophys Res Commun. 1998; 244 178-182
- 42 Pugh R N, Murray-Lyon I M, Dawson J L, Pietroni M C, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973; 60 646-649
- 43 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . . Diabetes Care. 1997; 20 1183-1197
- 44 Rosemurgy A S, Zervos E E, Goode S E, Black T J, Zwiebel B R. Differential effects on portal and effective hepatic blood flow. A comparison between transjugular intrahepatic portosystemic shunt and small-diameter H-graft portacaval shunt. Ann Surg. 1997; 225 601-607
- 45 Rosenbaum M, Leibel R L. The role of leptin in human physiology. N Engl J Med. 1999; 341 913-915
- 46 Rosenbaum M, Nicolson M, Hirsch J, Heymsfield S B, Gallagher D, Chu F, Leibel R L. Effects of gender, body composition, and menopause on plasma concentrations of leptin. J Clin Endocrinol Metab. 1996; 81 3424-3427
- 47 Saladin R, De Vos P, Guerre-Millo M, Leturque A, Girare J, Staels B, Auwerx J. Transient increase in obese gene expression after food intake or insulin administration. Nature. 1995; 377 527-529
- 48 Sanyal A J, Freedman A M, Luketic V A. Purdum PP 3rd . The natural history of portal hypertension after transjugular intrahepatic portosystemic shunts. Gastroenterology. 1997; 112 889-898
- 49 Sarraf P, Fredereich R C, Turner E M, Ma G, Jaskowiak N T, Rivet 3rd D J. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role of inflammatory anorexia. J Exp Med. 1997; 185 171-175
- 50 Saxena N K, Ikeda K, Rockey D C, Friedman S L, Anania F A. Leptin in hepatic fibrosis: evidence for increased collagen production in stellate cells and lean littermates of ob/ob mice. Hepatology. 2002; 35 762-771
- 51 Schuetz T, Zillich D P, Jurczak S, Ertel S, Lochs H, Plauth M. Improvement in body composition after transjugular intrahepatic portosystemic stent-shunt (TIPS) in patients with liver cirrhosis. Gastroenterology. 1999; 116 L0414
- 52 Shimizu H, Kakizaki S, Tsuchiya T, Nagamine T, Takagi H, Takayama H, Kobayashi I, Mori M. An increase of circulating leptin in patients with liver cirrhosis. Int J Obes Relat Metab Disord. 1998; 22 1234-1238
- 53 Sobhani I, Buyse M, Goiot H, Weber N, Laigneau J P, Henin D, Soul J C, Bado A. Vagal stimulation rapidly increases leptin secretion in human stomach. Gastroenterology. 2002; 122 259-263
- 54 Stenvinkel P, Lindholm B, Lönnqvist F, Katzarski K, Heimbürer O. Increases in serum leptin levels during peritoneal dialysis are associated with inflammation and a decrease in lean body mass. J Am Soc Nephrol. 2000; 11 1303-1309
- 55 Testa R, Franceschini R, Giannini E, Cataldi A, Botta F, Fasoli A, Tenerelli P, Rolandi E, Barreca T. Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis. J Hepatol. 2000; 33 33-37
- 56 Weigle D S, Duell P B, Connor W E, Steiner R A, Soules M R, Kuijper J. Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab. 1997; 82 561-565
- 57 Zumbach M S, Boheme M W, Wahl P, Stremmel W, Ziegler R, Nawroth P P. Tumor necrosis factor increases serum leptin levels in humans. J Clin Endocrinol Metabl. 1997; 82 4080-4082
1 The first two authors contributed equally to this paper.
M. D. M. Wirtz
Chirurgische Universitätsklinik
Abteilung für Allgemein-, Viszeral- und Unfallchirurgie
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M. D. W. Nolte
Medizinische Universitätsklinik
Abteilung für Gastroenterologie und Endokrinologie
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