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Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome

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Abstract

Terlipressin is an analog of the natural hormone arginine-vasopressin. It is used in the treatment of patients with cirrhosis and bleeding esophageal varices (BEV) and in patients with hepatorenal syndrome (HRS): two of the most dramatic and feared complications of cirrhosis. Terlipressin exerts its main pharmacological effect through stimulation of vasopressin-1 receptors. These receptors are located in vascular smooth muscle and mediate vasoconstriction. In patients with cirrhosis and portal hypertension, treatment with terlipressin increases mean arterial pressure and decreases portal flow and pressure within minutes of administration. Furthermore, in patients with ascites terlipressin improves glomerular filtration and excretion of sodium. Terlipressin decreases failure of initial hemostasis by 34%, decreases mortality by 34%, and is considered a first-line treatment for BEV, when available. Terlipressin in combination with albumin reverses type 1 HRS in 33%–60% of cases and is the only treatment with proven efficacy in randomized trials. The safety profile is favorable when considering the clinical efficacy and the high mortality of these clinical entities. Adverse events are mostly cardiovascular and related to vasoconstriction. Mortality and withdrawal of terlipressin due to adverse events occurs in less than 1% of cases. Mild adverse events related to terlipressin treatment occur in 10%–20% of patients. The benefit, however, of terlipressin on long-term survival in HRS remains to be determined. At present, treatment with terlipressin and albumin is considered the most efficient therapy and should therefore be recommended for the treatment of type 1 HRS-1.

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References

  1. Gines P, Quintero E, Arroyo V, et al. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987;7: 122–128.

    Article  PubMed  CAS  Google Scholar 

  2. Colle I, Durand F, Pessione F, et al. Clinical course, predictive factors and prognosis in patients with cirrhosis and type 1 hepatorenal syndrome treated with terlipressin: a retrospective analysis. J Gastroenterol Hepatol. 2002;17:882–888.

    Article  PubMed  Google Scholar 

  3. Carbonell N, Pauwels A, Serfaty L, Fourdan O, Levy VG, Poupon R. Improved survival after variceal bleeding in patients with cirrhosis over the past two decades. Hepatology. 2004;40:652–659.

    Article  PubMed  Google Scholar 

  4. McCormick PA, O’Keefe C. Improving prognosis following a first variceal haemorrhage over four decades. Gut. 2001;49:682–685.

    Article  PubMed  CAS  Google Scholar 

  5. Freeman JG, Cobden I, Lishman AH, Record CO. Controlled trial of terlipressin (’Glypressin’) versus vasopressin in the early treatment of oesophageal varices. Lancet. 1982;2:66–68.

    Article  PubMed  CAS  Google Scholar 

  6. Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet. 2003;362:1819–1827.

    Article  PubMed  CAS  Google Scholar 

  7. Martín-Llahí M, Pepin MN, Guevara M, et al. Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology. 2008;134:1352–1359.

    Article  PubMed  CAS  Google Scholar 

  8. Neri S, Pulvirenti D, Malaguarnera M, et al. Terlipressin and albumin in patients with cirrhosis and type I hepatorenal syndrome. Dig Dis Sci. 2008;53:830–835.

    Article  PubMed  CAS  Google Scholar 

  9. Sanyal AJ, Boyer T, Garcia-Tsao G, et al. A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome. Gastroenterology. 2008;134:1360–1368.

    Article  PubMed  CAS  Google Scholar 

  10. D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–231.

    Article  PubMed  Google Scholar 

  11. Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG. Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liver Dis. 2006;26:348–362.

    Article  PubMed  Google Scholar 

  12. Abraldes JG, Villanueva C, Banares R, et al. Hepatic venous pressure gradient and prognosis in patients with acute variceal bleeding treated with pharmacologic and endoscopic therapy. J Hepatol. 2008;48: 229–236.

    Article  PubMed  Google Scholar 

  13. Ripoll C, Groszmann R, Garcia-Tsao G, et al. Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. Gastroenterology. 2007;133:481–488.

    Article  PubMed  CAS  Google Scholar 

  14. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960–974.

    Article  PubMed  Google Scholar 

  15. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–851.

    Article  PubMed  CAS  Google Scholar 

  16. Pinzani M, Gentilini P. Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. Semin Liver Dis. 1999;19:397–410.

    Article  PubMed  CAS  Google Scholar 

  17. Groszmann RJ, Abraldes JG. Portal hypertension: from bedside to bench. J Clin Gastroenterol. 2005;39:S125–S130.

    Article  PubMed  Google Scholar 

  18. D’Amico G, de Franchis R. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology. 2003;38:599–612.

    Article  PubMed  Google Scholar 

  19. The North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med. 1988;319:983–989.

    Google Scholar 

  20. Bambha K, Kim WR, Pedersen RA, Bida JP, Kremers WK, Kamath PS. Predictors of rebleeding and mortality following acute variceal hemorrhage in patients with cirrhosis. Gut. 2008;57:814–820.

    Article  PubMed  CAS  Google Scholar 

  21. Bendtsen F, Krag A, Møller S. Treatment of acute variceal bleeding. Dig Liver Dis. 2008;40:328–336.

    Article  PubMed  CAS  Google Scholar 

  22. de Franchis R, Primignani M. Endoscopic treatments for portal hypertension. Semin Liver Dis. 1999;19:439–455.

    Article  PubMed  Google Scholar 

  23. Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology. 1999;29:1655–1661.

    Article  PubMed  CAS  Google Scholar 

  24. D’Amico G, Luca A. TIPS is a cost effective alternative to surgical shunt as a rescue therapy for prevention of recurrent bleeding from esophageal varices. J Hepatol. 2008;48:387–390.

    Article  PubMed  Google Scholar 

  25. Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology. 1981;80:800–809.

    PubMed  CAS  Google Scholar 

  26. Stokkeland K, Brandt L, Ekbom A, Hultcrantz R. Improved prognosis for patients hospitalized with esophageal varices in Sweden 1969-2002. Hepatology. 2006;43:500–505.

    Article  PubMed  Google Scholar 

  27. Garcia-Pagan JC, Escorsell A, Moitinho E, Bosch J. Influence of pharmacological agents on portal hemodynamics: basis for its use in the treatment of portal hypertension. Semin Liver Dis. 1999;19:427–438.

    Article  PubMed  CAS  Google Scholar 

  28. D’Amico G, Pietrosi G, Tarantino I, Pagliaro L. Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis: a Cochrane meta-analysis. Gastroenterology. 2003;124:1277–1291.

    Article  PubMed  CAS  Google Scholar 

  29. Kowalski HJ, Abelmann WH. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest. 1953;32:1025–1033.

    Article  PubMed  CAS  Google Scholar 

  30. Hecker R, Sherlock S. Electrolyte and circulatory changes in terminal liver failure. Lancet. 1956;271:1121–1125.

    Article  PubMed  CAS  Google Scholar 

  31. Schrier RW, Arroyo V, Bernardi M, Epstein M, Henriksen JH, Rodes J. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8:1151–1157.

    Article  PubMed  CAS  Google Scholar 

  32. Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule. Hepatology. 2006;43:S121–S131.

    Article  PubMed  CAS  Google Scholar 

  33. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646–1654.

    Article  PubMed  CAS  Google Scholar 

  34. Schrier RW. Decreased effective blood volume in edematous disorders: what does this mean? J Am Soc Nephrol. 2007;18: 2028–2031.

    Article  PubMed  Google Scholar 

  35. Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis: pathophysiological basis of therapy and current management. J Hepatol. 2003;38(suppl. 1):S69–S89.

    Article  PubMed  Google Scholar 

  36. Ruiz-del-Arbol L, Urman J, Fernandez J, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003;38:1210–1218.

    Article  PubMed  Google Scholar 

  37. Ruiz-del-Arbol L, Monescillo A, Arocena C, et al. Circulatory function and hepatorenal syndrome in cirrhosis. Hepatology. 2005;42:439–447.

    Article  PubMed  CAS  Google Scholar 

  38. Epstein M, Berk DP, Hollenberg NK, et al. Renal failure in the patient with cirrhosis. The role of active vasoconstriction. Am J Med. 1970;49:175–185.

    Article  PubMed  CAS  Google Scholar 

  39. Arroyo V, Terra C, Gines P. Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome. J Hepatol. 2007;46:935–946.

    Article  PubMed  CAS  Google Scholar 

  40. Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56:1310–1318.

    Article  PubMed  CAS  Google Scholar 

  41. Alessandria C, Ottobrelli A, Bernardi-Venon W, et al. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007;47:499–505.

    Article  PubMed  CAS  Google Scholar 

  42. Halimi C, Bonnard P, Bernard B, et al. Effect of terlipressin (Glypressin) on hepatorenal syndrome in cirrhotic patients: results of a multicentre pilot study. Eur J Gastroenterol Hepatol. 2002;14:153–158.

    Article  PubMed  CAS  Google Scholar 

  43. Moreau R, Durand F, Poynard T, et al. Terlipressin in patients with cirrhosis and type 1 hepatorenal syndrome: a retrospective multicenter study. Gastroenterology. 2002;122:923–930.

    Article  PubMed  CAS  Google Scholar 

  44. Mulkay JP, Louis H, Donckier V, et al. Longterm terlipressin administration improves renal function in cirrhotic patients with type 1 hepatorenal syndrome: a pilot study. Acta Gastroenterol Belg. 2001;64:15–19.

    PubMed  CAS  Google Scholar 

  45. Ortega R, Gines P, Uriz J, et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology. 2002;36:941–948.

    PubMed  CAS  Google Scholar 

  46. Sharma P, Kumar A, Shrama BC, Sarin SK. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103:1689–1697.

    Article  PubMed  CAS  Google Scholar 

  47. Solanki P, Chawla A, Garg R, Gupta R, Jain M, Sarin SK. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol. 2003;18:152–156.

    Article  PubMed  CAS  Google Scholar 

  48. Testro AG, Wongseelashote S, Angus PW, Gow PJ. Long-term outcome of patients treated with terlipressin for types 1 and 2 hepatorenal syndrome. J Gastroenterol Hepatol. 2007;23:1535–1540.

    Article  CAS  Google Scholar 

  49. Forsling ML, Aziz LA, Miller M, Davies R, Donovan B. Conversion of triglycylvasopressin to lysine-vasopressin in man. J Endocrinol. 1980;85:237–244.

    PubMed  CAS  Google Scholar 

  50. Nilsson G, Lindblom P, Ohlin M, Berling R, Vernersson E. Pharmacokinetics of terlipressin after single i.v. doses to healthy volunteers. Drugs Exp Clin Res. 1990;16:307–314.

    PubMed  CAS  Google Scholar 

  51. Holmes CL, Landry DW, Granton JT. Science review: vasopressin and the cardiovascular system part 1-receptor physiology. Crit Care. 2003;7:427–434.

    Article  PubMed  Google Scholar 

  52. Krag A, Møller S, Henriksen JH, Holstein-Rathlou NH, Larsen FS, Bendtsen F. Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome. Hepatology. 2007;46:1863–1871.

    Article  PubMed  CAS  Google Scholar 

  53. Hirasawa A, Shibata K, Kotosai K, Tsujimoto G. Cloning, functional expression and tissue distribution of human cDNA for the vascular-type vasopressin receptor. Biochem Biophys Res Commun. 1994;203:72–79.

    Article  PubMed  CAS  Google Scholar 

  54. Walker BR, Childs ME, Adams EM. Direct cardiac effects of vasopressin: role of V1-and V2-vasopressinergic receptors. Am J Physiol. 1988;255:H261–H265.

    PubMed  CAS  Google Scholar 

  55. Boyle WA 3rd, Segel LD. Direct cardiac effects of vasopressin and their reversal by a vascular antagonist. Am J Physiol. 1986;251:H734–H741.

    PubMed  CAS  Google Scholar 

  56. Barrett LK, Singer M, Clapp LH. Vasopressin: mechanisms of action on the vasculature in health and in septic shock. Crit Care Med. 2007;35:33–40.

    Article  PubMed  CAS  Google Scholar 

  57. Treschan TA, Peters J. The vasopressin system: physiology and clinical strategies. Anesthesiology. 2006;105:599–612.

    Article  PubMed  CAS  Google Scholar 

  58. Fenton RA, Knepper MA. Mouse models and the urinary concentrating mechanism in the new millennium. Physiol Rev. 2007;87:1083–1112.

    Article  PubMed  CAS  Google Scholar 

  59. Nielsen S, Frøkiær J, Marples D, Kwon TH, Agre P, Knepper MA. Aquaporins in the kidney: from molecules to medicine. Physiol Rev. 2002;82:205–244.

    PubMed  CAS  Google Scholar 

  60. Møller S, Hansen EF, Becker U, Brinch K, Henriksen JH, Bendtsen F. Central and systemic haemodynamic effects of terlipressin in portal hypertensive patients. Liver. 2000;20:51–59.

    Article  PubMed  Google Scholar 

  61. Romero G, Kravetz D, Argonz J, Bildozola M, Suarez A, Terg R. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol. 2000;32:419–425.

    Article  PubMed  CAS  Google Scholar 

  62. Kiszka-Kanowitz M, Henriksen JH, Hansen EF, Møller S, Bendtsen F. Effect of terlipressin on blood volume distribution in patients with cirrhosis. Scand J Gastroenterol. 2004;39:486–492.

    Article  PubMed  CAS  Google Scholar 

  63. Merkel C, Gatta A, Bolognesi M, et al. Hemodynamic changes of systemic, hepatic, and splenic circulation following triglycyllysin-vasopressin administration in alcoholic cirrhosis. Dig Dis Sci. 1988;33:1103–1109.

    Article  PubMed  CAS  Google Scholar 

  64. Hansen EF, Bendtsen F, Brinch K, Møller S, Henriksen JH, Becker U. Endoscopic Doppler ultrasound for measurement of azygos blood flow. Validation against thermodilution and assessment of pharmacological effects of terlipressin in portal hypertension. Scand J Gastroenterol. 2001;36:318–325.

    Article  PubMed  CAS  Google Scholar 

  65. Baik SK, Jeong PH, Ji SW, et al. Acute hemodynamic effects of octreotide and terlipressin in patients with cirrhosis: a randomized comparison. Am J Gastroenterol. 2005;100:631–635.

    Article  PubMed  CAS  Google Scholar 

  66. Escorsell A, Bandi JC, Moitinho E, et al. Time profile of the haemodynamic effects of terlipressin in portal hypertension. J Hepatol. 1997;26:621–627.

    Article  PubMed  CAS  Google Scholar 

  67. Lin HC, Yang YY, Hou MC, et al. Hemodynamic effects of a combination of octreotide and terlipressin in patients with viral hepatitis related cirrhosis. Scand J Gastroenterol. 2002;37:482–487.

    Article  PubMed  CAS  Google Scholar 

  68. Escorsell A, Bandi JC, Andreu V, et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology. 2001;120:161–169.

    Article  PubMed  CAS  Google Scholar 

  69. Villanueva C, Planella M, Aracil C, et al. Hemodynamic effects of terlipressin and high somatostatin dose during acute variceal bleeding in nonresponders to the usual somatostatin dose. Am J Gastroenterol. 2005;100:624–630.

    Article  PubMed  CAS  Google Scholar 

  70. Nevens F, Van SW, Yap SH, Fevery J. Assessment of variceal pressure by continuous non-invasive endoscopic registration: a placebo controlled evaluation of the effect of terlipressin and octreotide. Gut. 1996;38:129–134.

    Article  PubMed  CAS  Google Scholar 

  71. Cestari R, Braga M, Missale G, Ravelli P, Burroughs AK. Haemodynamic effect of triglycyl-lysine-vasopressin (glypressin) on intravascular oesophageal variceal pressure in patients with cirrhosis. A randomized placebo controlled trial. J Hepatol. 1990;10:205–210.

    Article  PubMed  CAS  Google Scholar 

  72. Lote CJ, McVicar AJ, Thewles A. Renal haemodynamic actions of pressor doses of lysine vasopressin in the rat. J Physiol. 1987;391:407–418.

    PubMed  CAS  Google Scholar 

  73. Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG. Association of beta-arrestin with G protein-coupled receptors during clathrinmediated endocytosis dictates the profile of receptor resensitization. J Biol Chem. 1999;274:32248–32257.

    Article  PubMed  CAS  Google Scholar 

  74. Krag A, Bendtsen F, Pedersen EB, Holstein-Rathlou NH, Moller S. Effects of terlipressin on the aquaretic system-evidence of antidiuretic effects. Am J Physiol Renal Physiol. 2008 [Epub ahead of print]

  75. Nadvornikova H, Schuck O. The influence of a single dose of vasopressin analogs on human renal potassium excretion. Int J Clin Pharmacol Ther Toxicol. 1982;20:155–158.

    PubMed  CAS  Google Scholar 

  76. Stephan F, Paillard F. Terlipressinexacerbated hypokalaemia. Lancet. 1998;351:1249–1250.

    Article  PubMed  CAS  Google Scholar 

  77. de Franchis R. Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension. J Hepatol. 2005;43:167–176.

    Article  PubMed  Google Scholar 

  78. Ioannou GN, Doust J, Rockey DC. Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther. 2003;17:53–64.

    Article  PubMed  CAS  Google Scholar 

  79. Hu RH, Lee PH. Open, randomized, comparative study of efficacy and safety between Haemopressin and Glypressin in treating acute esophageal varices hemorrhage. Hepatogastroenterology. 2008;55:448–452.

    PubMed  CAS  Google Scholar 

  80. Bruha R, Marecek Z, Spicak J, et al. Doubleblind randomized, comparative multicenter study of the effect of terlipressin in the treatment of acute esophageal variceal and/or hypertensive gastropathy bleeding. Hepatogastroenterology. 2002;49:1161–1166.

    PubMed  CAS  Google Scholar 

  81. Levacher S, Letoumelin P, Pateron D, Blaise M, Lapandry C, Pourriat JL. Early administration of terlipressin plus glyceryl trinitrate to control active upper gastrointestinal bleeding in cirrhotic patients. Lancet. 1995;346:865–868.

    Article  PubMed  CAS  Google Scholar 

  82. Söderlund C, Magnusson I, Torngren S, Lundell L. Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial. Scand J Gastroenterol. 1990;25:622–630.

    Article  PubMed  Google Scholar 

  83. Walker S, Stiehl A, Raedsch R, Kommerell B. Terlipressin in bleeding esophageal varices: a placebo-controlled, double-blind study. Hepatology. 1986;6:112–115.

    Article  PubMed  CAS  Google Scholar 

  84. Pauwels A, Florent C, Desaint B, Van Guivarch PH, Levy VG. Terlipressin and somatostatin in the treatment of hemorrhages from rupture of esophageal varices (letter) [French]. Gastroenterologie Clinique Biologique. 1994;18:388–389.

    CAS  Google Scholar 

  85. Brunati X, Ceriani R, Curioni R, Brunelli L, Repaci G, Morini L. Sclerotherapy alone vs scherotherapy plus terlipressin vs sclerotherapy plus octreotide in the treatment of acute variceal hemorrhage. Hepatology. 1996;24:207A.

    Google Scholar 

  86. Patch D, Caplin M, Greenslade L, Burroughs A. Randomized double blind controlled trial of 5 day terlipressin vs placebo in acute variceal hemorrhage. J Hepatol. 1999;30(suppl. 1):55.

    Google Scholar 

  87. Garcia-Tsao G, Groszmann RJ. Portal hemodynamics during nitroglycerin administration in cirrhotic patients. Hepatology. 1987;7:805–809.

    Article  PubMed  CAS  Google Scholar 

  88. Moitinho E, Planas R, Banares R, et al. Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding. J Hepatol. 2001;35:712–718.

    Article  PubMed  CAS  Google Scholar 

  89. Ottesen LH, Flyvbjerg A, Møller S, Bendtsen F. The organ extraction and splanchnic haemodynamic effects of octreotide in cirrhotic patients. Aliment Pharmacol Ther. 1998;12:657–665.

    Article  PubMed  CAS  Google Scholar 

  90. Møller S, Brinch K, Henriksen JH, Becker U. Effect of octreotide on systemic, central, and splanchnic haemodynamics in cirrhosis. J Hepatol. 1997;26:1026–1033.

    Article  PubMed  Google Scholar 

  91. Gotzsche PC, Hrobjartsson A. Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database Syst Rev. 2008;(3):CD000193.

    PubMed  Google Scholar 

  92. Banares R, Albillos A, Rincon D, et al. Endoscopic treatment versus endoscopic plus pharmacologic treatment for acute variceal bleeding: a meta-analysis. Hepatology. 2002;35:609–615.

    Article  PubMed  Google Scholar 

  93. Fort E, Sautereau D, Silvain C, Ingrand P, Pillegand B, Beauchant M. A randomized trial of terlipressin plus nitroglycerin vs. balloon tamponade in the control of acute variceal hemorrhage. Hepatology. 1990;11:678–681.

    Article  PubMed  CAS  Google Scholar 

  94. Garcia-Compean D, Blanc P, Bories JM, et al. Treatment of active gastroesophageal variceal bleeding with terlipressin or hemostatic balloon in patients with cirrhosis. A randomized controlled trial. Arch Med Res. 1997;28:241–245.

    PubMed  CAS  Google Scholar 

  95. Colin R, Giuli N, Czernichow P, et al. Prospective comparison of glypressin, tamponade and their association in the treatment of bleeding esophageal varices. In: Lebrec, D, Blei, AT, eds. Vasopressin Analogs and Portal Hypertension. Paris: John Libbey Eurotext; 1987:149–153.

    Google Scholar 

  96. Pedretti G, Elia G, Calzetti C, Magnani G, Fiaccadori F. Octreotide versus terlypressin in acute variceal hemorrhage in liver cirrhosis. Emergency control and prevention of early rebleeding. Clin Investig. 1994;72:653–659.

    Article  PubMed  CAS  Google Scholar 

  97. Silvain C, Carpentier S, Sautereau D, et al. Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multicenter randomized trial. Hepatology. 1993;18:61–65.

    PubMed  CAS  Google Scholar 

  98. Walker S, Kreichgauer HP, Bode JC. Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices-final report of a placebo-controlled, double-blind study. Gastroenterol. 1996;34:692–698.

    CAS  Google Scholar 

  99. Feu F, Ruiz del Arbol L, Banares R, Planas R, Bosch J. Double-blind randomized controlled trial comparing terlipressin and somatostatin for acute variceal hemorrhage. Variceal Bleeding Study Group. Gastroenterology. 1996;111:1291–1299.

    Article  PubMed  CAS  Google Scholar 

  100. Escorsell A, Ruiz del Arbol L, Planas R, et al. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Hepatology. 2000;32:471–476.

    Article  PubMed  CAS  Google Scholar 

  101. Wechowski J, Connolly M, Woehl A, et al. An economic evaluation of vasoactive agents used in the United Kingdom for acute bleeding oesophageal varices in patients with liver cirrhosis. Curr Med Res Opin. 2007;23:1481–1491.

    Article  PubMed  Google Scholar 

  102. Connolly M, Bhatt A, Wechowski J, Colle I. An economic evaluation of vasoactive agents used to treat acute bleeding oesophageal varices in Belgium. Acta Gastroenterol Belg. 2008;71:230–236.

    PubMed  Google Scholar 

  103. Angeli P, Merkel C. Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis. J Hepatol. 2008;48(suppl. 1):S93–S103.

    Article  PubMed  CAS  Google Scholar 

  104. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996;23:164–176.

    Article  PubMed  CAS  Google Scholar 

  105. Duvoux C, Zanditenas D, Hezode C, et al. Effects of noradrenalin and albumin in patients with type I hepatorenal syndrome: a pilot study. Hepatology. 2002;36:374–380.

    Article  PubMed  CAS  Google Scholar 

  106. Restuccia T, Ortega R, Guevara M, et al. Effects of treatment of hepatorenal syndrome before transplantation on posttransplantation outcome. A case-control study. J Hepatol. 2004;40:140–146.

    Article  PubMed  Google Scholar 

  107. Barcroft H, Konzett H. On the actions of noradrenaline, adrenaline and isopropyl noradrenaline on the arterial blood pressure, heart rate and muscle blood flow in man. J Physiol. 1949;110:194–204.

    PubMed  CAS  Google Scholar 

  108. Swan HJ. Noradrenaline, adrenaline, and the human circulation. BMJ. 1952;1:1003–1006.

    PubMed  CAS  Google Scholar 

  109. Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or foes? Crit Care. 2001;5:294–298.

    Article  PubMed  CAS  Google Scholar 

  110. Pittner H, Turnheim K. Pulmonary and systemic circulatory effects of midodrine, a new sympathomimetic, and its metabolite, ST 1059. Arch Int Pharmacodyn Ther. 1974;207:180–192.

    PubMed  CAS  Google Scholar 

  111. Angeli P, Volpin R, Piovan D, et al. Acute effects of the oral administration of midodrine, an alpha-adrenergic agonist, on renal hemodynamics and renal function in cirrhotic patients with ascites. Hepatology. 1998;28:937–943.

    Article  PubMed  CAS  Google Scholar 

  112. Kalambokis G, Economou M, Fotopoulos A, et al. The effects of chronic treatment with octreotide versus octreotide plus midodrine on systemic hemodynamics and renal hemodynamics and function in nonazotemic cirrhotic patients with ascites. Am J Gastroenterol. 2005;100:879–885.

    Article  PubMed  CAS  Google Scholar 

  113. Kalambokis G, Fotopoulos A, Economou M, Pappas K, Tsianos EV. Effects of a 7-day treatment with midodrine in non-azotemic cirrhotic patients with and without ascites. J Hepatol. 2007;46:213–221.

    Article  PubMed  CAS  Google Scholar 

  114. Angeli P, Volpin R, Gerunda G, et al. Reversal of type 1 hepatorenal syndrome with the administration of midodrine and octreotide. Hepatology. 1999;29:1690–1697.

    Article  PubMed  CAS  Google Scholar 

  115. Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004;40:55–64.

    Article  PubMed  CAS  Google Scholar 

  116. Esrailian E, Pantangco ER, Kyulo NL, Hu KQ, Runyon BA. Octreotide/midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci. 2007;52:742–748.

    Article  PubMed  CAS  Google Scholar 

  117. Pomier-Layrargues G, Paquin SC, Hassoun Z, Lafortune M, Tran A. Octreotide in hepatorenal syndrome: a randomized, double-blind, placebo-controlled, crossover study. Hepatology. 2003;38:238–243.

    Article  PubMed  CAS  Google Scholar 

  118. Ottesen LH, Aagaard NK, Kiszka-Kanowitz M, et al. Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial. Hepatology. 2001;34:471–477.

    Article  PubMed  CAS  Google Scholar 

  119. Kiser TH, Fish DN, Obritsch MD, Jung R, MacLaren R, Parikh CR. Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: a retrospective study. Nephrol Dial Transplant. 2005;20:1813–1820.

    Article  PubMed  CAS  Google Scholar 

  120. Gines P, Tito L, Arroyo V, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology. 1988;94:1493–1502.

    PubMed  CAS  Google Scholar 

  121. Moreau R, Asselah T, Condat B, et al. Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study. Gut. 2002;50:90–94.

    Article  PubMed  CAS  Google Scholar 

  122. Lata J, Marecek Z, Fejfar T, et al. The efficacy of terlipressin in comparison with albumin in the prevention of circulatory changes after the paracentesis of tense ascites-a randomized multicentric study. Hepatogastroenterology. 2007;54:1930–1933.

    PubMed  CAS  Google Scholar 

  123. Singh V, Dheerendra PC, Singh B, et al. Midodrine versus albumin in the prevention of paracentesis-induced circulatory dysfunction in cirrhotics: a randomized pilot study. Am J Gastroenterol. 2008;103:1399–1405.

    Article  PubMed  CAS  Google Scholar 

  124. Eefsen M, Dethloff T, Frederiksen HJ, Hauerberg J, Hansen BA, Larsen FS. Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support. J Hepatol. 2007;47:381–386.

    Article  PubMed  CAS  Google Scholar 

  125. Shawcross DL, Davies NA, Mookerjee RP, et al. Worsening of cerebral hyperemia by the administration of terlipressin in acute liver failure with severe encephalopathy. Hepatology. 2004;39:471–475.

    Article  PubMed  CAS  Google Scholar 

  126. Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev. 2003;(1):CD002147.

    PubMed  Google Scholar 

  127. D’Amico G, Traina M, Vizzini G et al. Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis. A randomized clinical trial. Liver Study Group of V. Cervello Hospital. J Hepatol. 1994;20:206–212.

    Article  PubMed  CAS  Google Scholar 

  128. Sanyal AJ, Bosch J, Blei A, Arroyo V. Portal hypertension and its complications. Gastroenterology. 2008;134:1715–1728.

    Article  PubMed  Google Scholar 

  129. Gulberg V, Bilzer M, Gerbes AL. Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine. Hepatology. 1999;30:870–875.

    Article  PubMed  CAS  Google Scholar 

  130. Guevara M, Gines P, Fernandez-Esparrach G, et al. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology. 1998;27:35–41.

    Article  PubMed  CAS  Google Scholar 

  131. Lee MY, Chu CS, Lee KT, et al. Terlipressinrelated acute myocardial infarction: a case report and literature review. Kaohsiung J Med Sci. 2004;20:604–608.

    PubMed  Google Scholar 

  132. Rosario R, Lalanne B, Lebre P, et al. Myocardial infarction after injection of terlipressin for digestive hemorrhage. Gastroenterol Clin Biol. 1996;20:712–713.

    PubMed  CAS  Google Scholar 

  133. Urge J, Sincl F, Prochazka V, Urbanek K. Terlipressin-induced ventricular arrhythmia. Scand J Gastroenterol. 2008;43:1145–1148.

    Article  PubMed  CAS  Google Scholar 

  134. Kelly KJ, Stang JM, Mekhjian HS. Vasopressin provocation of ventricular dysrhythmia. Ann Intern Med. 1980;92:205–206.

    PubMed  CAS  Google Scholar 

  135. Eden E, Teirstein A, Wiener I. Ventricular arrhythmia induced by vasopressin: torsade de pointes related to vasopressin-induced bradycardia. Mt Sinai J Med. 1983;50:49–51.

    PubMed  CAS  Google Scholar 

  136. Mauro VF, Bingle JF, Ginn SM, Jafri FM. Torsade de pointes in a patient receiving intravenous vasopressin. Crit Care Med. 1988;16:200–201.

    Article  PubMed  CAS  Google Scholar 

  137. Kupferschmidt H, Meier CH, Sulzer M, Meier PJ, Buhler H. Clinicopharmacological case. Bradycardia and ventricular tachycardia of the torsades de pointes type as a side effect of vasopressin: 3 case reports. Praxis. 1996;85:340–343.

    PubMed  CAS  Google Scholar 

  138. Faigel DO, Metz DC, Kochman ML. Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol. 1995;90:822–824.

    PubMed  CAS  Google Scholar 

  139. Stein LB, Dabezies MA, Silverman M, Brozena SC. Fatal torsade de pointes occurring in a patient receiving intravenous vasopressin and nitroglycerin. J Clin Gastroenterol. 1992;15:171–174.

    Article  PubMed  CAS  Google Scholar 

  140. Klein GJ. Vasopressin, “torsades de pointes”, and QT syndrome. Ann Intern Med. 1980;93:511–512.

    PubMed  CAS  Google Scholar 

  141. Ouattara A, Landi M, Le MY, et al. Comparative cardiac effects of terlipressin, vasopressin, and norepinephrine on an isolated perfused rabbit heart. Anesthesiology. 2005;102:85–92.

    Article  PubMed  CAS  Google Scholar 

  142. Wu IC, Yu FJ, Chou JJ, et al. Predictive risk factors for upper gastrointestinal bleeding with simultaneous myocardial injury. Kaohsiung J Med Sci. 2007;23:8–16.

    Article  PubMed  Google Scholar 

  143. Di Micoli A, Bracci E, Cappa FM, et al. Terlipressin infusion induces ischemia of breast skin in a cirrothic patient with hepatorenal syndrome. Dig Liver Dis. 2008;40:304–305.

    Article  PubMed  Google Scholar 

  144. Donnellan F, Cullen G, Hegarty JE, McCormick PA. Ischaemic complications of Glypressin in liver disease: a case series. Br J Clin Pharmacol. 2007;64:550–552.

    Article  PubMed  Google Scholar 

  145. Lee JS, Lee HS, Jung SW, et al. A case of peripheral ischemic complication after terlipressin therapy. Korean J Gastroenterol. 2006;47:454–457.

    PubMed  Google Scholar 

  146. Vaccaro F, Giorgi A, Riggio O, De SA, Laviano A, Rossi-Fanelli F. Is spontaneous bacterial peritonitis an inducer of vasopressin analogue side-effects? A case report. Dig Liver Dis. 2003;35:503–506.

    Article  PubMed  CAS  Google Scholar 

  147. Oh JE, Ha JS, Cho DH, Yu GJ, Shim SG. A case of ischemic skin necrosis after glypressin therapy in liver cirrhosis. Korean J Gastroenterol. 2008;51:381–384.

    PubMed  Google Scholar 

  148. Willems MG, Schoenemann J, Rey C, Schafer H, Lindecken KD. Ischemia of the cecum caused by glycylpressin [in German]. Leber Magen Darm. 1985;15:165–168.

    PubMed  CAS  Google Scholar 

  149. Hansen M, Bjerg J, Gilsaa T. Terlipressin and reversible intestinal ischaemia [in Danish]. Ugeskr Laeger. 2007;169:1802–1803.

    PubMed  Google Scholar 

  150. Schmitt W, Wagner-Thiessen E, Lux G. Ischaemic colitis in a patient treated with glypressin for bleeding oesophageal varices. Hepatogastroenterology. 1987;34:134–136.

    PubMed  CAS  Google Scholar 

  151. Machova A. Antidiuretic activity of terlipressin (triglycyl-lysine vasopressin)-role of pressure natriuresis. Physiol Res. 1992;41:121–127.

    PubMed  CAS  Google Scholar 

  152. Douriez E, Mollard P, Laval C, Albengres E, Laporte JP, Tillement JP. Severe hyponatremia after repeated administration of terlipressin [in French]. Therapie. 1993;48:518–519.

    PubMed  CAS  Google Scholar 

  153. Dunwoodie E, Jowett S. Terlipressin causing a hyponatraemic seizure. Scand J Gastroenterol. 2007;42:665.

    Article  PubMed  Google Scholar 

  154. Chalasani N, Kahi C, Francois F, et al. Improved patient survival after acute variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003;98:653–659.

    Article  PubMed  Google Scholar 

  155. Alessandria C, Ozdogan O, Guevara M, et al. MELD score and clinical type predict prognosis in hepatorenal syndrome: relevance to liver transplantation. Hepatology. 2005;41:1282–1289.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Departments of Gastroenterology and Clinical Physiology, Hvidovre University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Aleksander Krag

  2. Department of Gastroenterology, Hvidovre University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Tine Borup & Flemming Bendtsen

  3. Department of Clinical Physiology, Hvidovre University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark

    Søren Møller

  4. Department of Medical Gastroenterology, 439 Hvidovre Hospital, DK-2650, Hvidovre, Denmark

    Aleksander Krag

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Krag, A., Borup, T., Møller, S. et al. Efficacy and safety of terlipressin in cirrhotic patients with variceal bleeding or hepatorenal syndrome. Adv Therapy 25, 1105–1140 (2008). https://doi.org/10.1007/s12325-008-0118-7

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