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Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices

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Abstract

Cirrhosis results in portal hypertension in many patients. The major complications of portal hypertension include development of ascites and esophageal or gastric varices. Varices lead to hemorrhage and death in a significant proportion of patients. This review focuses on the pharmacologic approach to management of portal hypertension in patients at risk of variceal hemorrhage, or those who have already had variceal bleeding. Pharmacologic therapy is used for 1) primary prevention of bleeding, 2) management of acute bleeding, and 3) prevention of recurrent bleeding (secondary prophylaxis). For acute esophageal variceal hemorrhage, a variety of pharmacologic agents are used, including somatostatin, octreotide, vapreotide, lanreotide, terlipressin, and vasopressin (with nitrates). For primary and secondary prevention of esophageal variceal hemorrhage, a-blockers remain the mainstay therapy.

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References and Recommended Reading

  1. 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. Demonstrates that outcomes appear to be improving-implying that implementation of newer therapeutics and intensive care has improved patient care.

    Article  PubMed  Google Scholar 

  2. van Leerdam ME, Vreeburg EM, Rauws EA, et al.: Acute upper GI bleeding: did anything change? Time trend analysis of incidence and outcome of acute upper GI bleeding between 1993/1994 and 2000. Am J Gastroenterol 2003, 98:1494–1499.

    Article  PubMed  Google Scholar 

  3. 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 

  4. Rockey DC: Vascular mediators in the injured liver. Hepatology 2003, 37:4–12. Includes a concise overview of the pathophysiologic basis of intrahepatic portal hypertension.

    Article  PubMed  CAS  Google Scholar 

  5. Viallet A, Marleau D, Huet M, et al.: Hemodynamic evaluation of patients with intrahepatic portal hypertension. Relationship between bleeding varices and the portohepatic gradient. Gastroenterology 1975, 69:1297–1300.

    PubMed  CAS  Google Scholar 

  6. Lebrec D, De Fleury P, Rueff B, et al.: Portal hypertension, size of esophageal varices, and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology 1980, 79:1139–1144. Emphasizes that the worse the liver disease, the larger the varices, and the more likely they are to bleed.

    PubMed  CAS  Google Scholar 

  7. Garcia-Tsao G, Groszmann RJ, Fisher RL, et al.: Portal pressure, presence of gastroesophageal varices and variceal bleeding. Hepatology 1985, 5:419–424. The seminal observation that esophageal varices bleed only after HVPG exceeds 12 mm Hg.

    Article  PubMed  CAS  Google Scholar 

  8. Cales P, Pascal JP: Gastroesophageal endoscopic features in cirrhosis: comparison of intracenter and intercenter observer variability. Gastroenterology 1990, 99:1189.

    PubMed  CAS  Google Scholar 

  9. Ng FH, Wong SY, Loo CK, et al.: Prediction of oesopha gogastric varices in patients with liver cirrhosis. J Gastroenterol Hepatol 1999, 14:785–790.

    Article  PubMed  CAS  Google Scholar 

  10. Chalasani N, Imperiale TF, Ismail A, et al.: Predictors of large esophageal varices in patients with cirrhosis. Am J Gastroenterol 1999, 94:3285–291. Low platelets and splenomegaly appear to be the most useful predictors of the presence of large varices.

    Article  PubMed  CAS  Google Scholar 

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

  12. Beppu K, Inokuchi K, Koyanagi N, et al.: Prediction of variceal hemorrhage by esophageal endoscopy. Gastrointest Endosc 1981, 27:213–218.

    PubMed  CAS  Google Scholar 

  13. Kleber G, Sauerbruch T, Ansari H, Paumgartner G: Prediction of variceal hemorrhage in cirrhosis: a prospective follow-up study. Gastroenterology 1991, 100:1332–1337.

    PubMed  CAS  Google Scholar 

  14. Sarin SK, Sundaram KR, Ahuja RK: Predictors of variceal bleeding: an analysis of clinical, endoscopic, and haemodynamic variables, with special reference to intravariceal pressure. Gut 1989, 30:1757–1764.

    PubMed  CAS  Google Scholar 

  15. Sharara AI, Rockey DC: Gastroesophageal variceal hemorrhage. N Engl J Med 2001, 345:669–681.

    Article  PubMed  CAS  Google Scholar 

  16. Boyer TD, Triger DR, Horisawa M, et al.: Direct transhepatic measurement of portal vein pressure using a thin needle. Comparison with wedged hepatic vein pressure. Gastroenterology 1977, 72:584–589.

    PubMed  CAS  Google Scholar 

  17. Merkel C, Bolognesi M, Bellon S, et al.: Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices. Gastroenterology 1992, 102:973–979.

    PubMed  CAS  Google Scholar 

  18. Villanueva C, Minana J, Ortiz J, et al.: Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding. N Engl J Med 2001, 345:647–655. Important study that additionally demonstrated that those patients with a hemodynamic response to a-blocker therapy have an extremely low risk of recurrent bleeding, emphasizing that physiologic assessment of portal pressure is critical.

    Article  PubMed  CAS  Google Scholar 

  19. Merkel C, Bolognesi M, Sacerdoti D, et al.: The hemodynamic response to medical treatment of portal hypertension as a predictor of clinical effectiveness in the primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000, 32:930–934.

    Article  PubMed  CAS  Google Scholar 

  20. Moitinho E, Escorsell A, Bandi JC, et al.: Prognostic value of early measurements of portal pressure in acute variceal bleeding. Gastroenterology 1999, 117:626–631.

    Article  PubMed  CAS  Google Scholar 

  21. Thalheimer U, Mela M, Patch D, Burroughs AK: Targeting portal pressure measurements: a critical reappraisal. Hepatology 2004, 39:286–290.

    Article  PubMed  Google Scholar 

  22. Boyer TD: Changing clinical practice with measurements of portal pressure. Hepatology 2004, 39:283–285.

    Article  PubMed  Google Scholar 

  23. 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 

  24. Schepis F, Camma C, Niceforo D, et al.: Which patients with cirrhosis should undergo endoscopic screening for esophageal varices detection? Hepatology 2001, 33:333–338.

    Article  PubMed  CAS  Google Scholar 

  25. D'Amico G, Pagliaro L, Bosch J: The treatment of portal hypertension: a meta-analytic review. Hepatology 1995, 22:332–354.

    Article  PubMed  Google Scholar 

  26. Feu F, Garcia-Pagan JC, Bosch J, et al.: Relation between portal pressure response to pharmacotherapy and risk of recurrent variceal haemorrhage in patients with cirrhosis. Lancet 1995, 346:1056–1059.

    Article  PubMed  CAS  Google Scholar 

  27. Lebrec D, Hillon P, Munoz C, et al.: The effect of propranolol on portal hypertension in patients with cirrhosis: a hemodynamic study. Hepatology 1982, 2:523–527.

    Article  PubMed  CAS  Google Scholar 

  28. Hayes PC, Davis JM, Lewis JA, Bouchier IA: Meta-analysis of value of propranolol in prevention of variceal haemorrhage. Lancet 1990, 336:153–156.

    Article  PubMed  CAS  Google Scholar 

  29. D'Amico G, Pagliaro L, Bosch J: Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999, 19:475–505.

    Article  PubMed  Google Scholar 

  30. Vlachogiannakos J, Goulis J, Patch D, Burroughs AK: Review article: primary prophylaxis for portal hypertensive bleeding in cirrhosis. Aliment Pharmacol Ther 2000, 14:851–860.

    Article  PubMed  CAS  Google Scholar 

  31. Teran JC, Imperiale TF, Mullen KD, et al.: Primary prophylaxis of variceal bleeding in cirrhosis: a costeffectiveness analysis. Gastroenterology 1997, 112:473–482.

    Article  PubMed  CAS  Google Scholar 

  32. Laine L, Cook D: Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995, 123:280–287.

    PubMed  CAS  Google Scholar 

  33. Sarin SK, Lamba GS, Kumar M, et al.: Comparison of endoscopic ligation and propranolol for the primary prevention of variceal bleeding. N Engl J Med 1999, 340:988–993.

    Article  PubMed  CAS  Google Scholar 

  34. De BK, Ghoshal UC, Das T, et al.: Endoscopic variceal ligation for primary prophylaxis of oesophageal variceal bleed: preliminary report of a randomized controlled trial. J Gastroenterol Hepatol 1999, 14:220–224.

    Article  PubMed  CAS  Google Scholar 

  35. Lui HF, Stanley AJ, Forrest EH, et al.: Primary prophylaxis of variceal hemorrhage: a randomized controlled trial comparing band ligation, propranolol, and isosorbide mononitrate. Gastroenterology 2002, 123:735–744.

    Article  PubMed  CAS  Google Scholar 

  36. Lo GH, Chen WC, Chen MH, et al.: Endoscopic ligation vs. nadolol in the prevention of first variceal bleeding in patients with cirrhosis. Gastrointest Endosc 2004, 59:333–338. The most recent in a series of studies comparing endoscopic band ligation and nadolol for primary prevention of esophageal variceal hemorrhage. This study demonstrated no difference in the two approaches.

    Article  PubMed  Google Scholar 

  37. Angelico M, Carli L, Piat C, et al.: Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis. Gastroenterology 1997, 113:1632–9.

    Article  PubMed  CAS  Google Scholar 

  38. Angelico M, Lionetti R: Long-acting nitrates in portal hypertension: to be or not to be? Dig Liver Dis 2001, 33:205–211.

    Article  PubMed  CAS  Google Scholar 

  39. Garcia-Pagan JC, Feu F, Bosch J, Rodes J: Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis: a randomized controlled study. Ann Intern Med 1991, 114:869–873.

    PubMed  CAS  Google Scholar 

  40. Merkel C, Marin R, Sacerdoti D, et al.: Long-term results of a clinical trial of nadolol with or without isosorbide mononitrate for primary prophylaxis of variceal bleeding in cirrhosis. Hepatology 2000, 31:324–329.

    Article  PubMed  CAS  Google Scholar 

  41. Bataller R, Gines P, Lora J, et al.: Evidence for a local renin-angiotensin system in human liver: Expression in activated hepatic stellate cells. Hepatology 2001, 34:399A.

    Google Scholar 

  42. Schneider AW, Kalk JF, Klein CP: Effect of losartan, an angiotensin II receptor antagonist, on portal pressure in cirrhosis. Hepatology 1999, 29:334–339.

    Article  PubMed  CAS  Google Scholar 

  43. Gonzalez-Abraldes J, Albillos A, Banares R, et al.: Randomized comparison of long-term losartan versus propranolol in lowering portal pressure in cirrhosis. Gastroenterology 2001, 121:382–388.

    Article  PubMed  CAS  Google Scholar 

  44. Conn HO, Ramsby GR, Storer EH, et al.: Intraarterial vasopressin in the treatment of upper gastrointestinal hemorrhage: a prospective, controlled clinical trial. Gastroenterology 1975, 68:211–221.

    PubMed  CAS  Google Scholar 

  45. Bosch J, Groszmann RJ, Garcia-Pagan JC, et al.: Association of transdermal nitroglycerin to vasopressin infusion in the treatment of variceal hemorrhage: a placebo-controlled clinical trial. Hepatology 1989, 10:962–968.

    Article  PubMed  CAS  Google Scholar 

  46. Levacher S, Letoumelin P, Pateron D, et al.: 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 

  47. Ioannou GN, Doust J, Rockey DC: Systematic review: terlipressin in acute oesophageal variceal haemorrhage. Aliment Pharmacol Ther 2003, 17:53–64. Demonstrated that terlipressin is the only pharmacologic agent that improves mortality when used in the setting of acute variceal bleeding.

    Article  PubMed  CAS  Google Scholar 

  48. Feu F, Ruiz del Arbol L, Banares R, et al.: 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 

  49. Corley DA, Cello JP, Adkisson W, et al.: Octreotide for acute esophageal variceal bleeding: a meta-analysis. Gastroenterology 2001, 120:946–954.

    Article  PubMed  CAS  Google Scholar 

  50. Besson I, Ingrand P, Person B, et al.: Sclerotherapy with or without octreotide for acute variceal bleeding. N Engl J Med 1995, 333:555–560.

    Article  PubMed  CAS  Google Scholar 

  51. Sung JJ, Chung SC, Yung MY, et al.: Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation. Lancet 1995, 346:1666–1669.

    Article  PubMed  CAS  Google Scholar 

  52. 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 

  53. de Franchis R, Primignani M: Why do varices bleed? Gastroenterol Clin North Am 1992, 21:85–101.

    PubMed  Google Scholar 

  54. Grace ND, Groszmann RJ, Garcia-Tsao G, et al.: Portal hypertension and variceal bleeding: an AASLD single topic symposium. Hepatology 1998, 28:868–880.

    Article  PubMed  CAS  Google Scholar 

  55. de Franchis R, Dellera A, Fazzini L, et al.: Evaluation and follow-up of patients with portal hypertension and oesophageal varices: how and when. Dig Liver Dis 2001, 33:643–646.

    Article  PubMed  Google Scholar 

  56. de Franchis R: Review article: definition and diagnosis in portal hypertension-continued problems with the Baveno consensus? Aliment Pharmacol Ther 2004, 20(Suppl 3):2–6, discussion 7.

    Article  PubMed  Google Scholar 

  57. Henderson JM, Boyer TD, Kutner MH, et al.: DSRS vs. TIPS for refractory variceal bleeding: a prospective randomized controlled trial. Hepatology 2004, 40:725A.

    Article  Google Scholar 

  58. Bernard B, Lebrec D, Mathurin P, et al.: Beta-adrenergic antagonists in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis. Hepatology 1997, 25:63–70.

    Article  PubMed  CAS  Google Scholar 

  59. Vinel JP, Lamouliatte H, Cales P, et al.: Propranolol reduces the rebleeding rate during endoscopic sclerotherapy before variceal obliteration. Gastroenterology 1992, 102:1760–3.

    PubMed  CAS  Google Scholar 

  60. Lo GH, Lai KH, Cheng JS, et al.: Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial. Hepatology 2000, 32:461–465.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, 75390-8887, Dallas, TX, USA

    Don C. Rockey MD

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Rockey, D.C. Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices. Curr Gastroenterol Rep 8, 7–13 (2006). https://doi.org/10.1007/s11894-006-0058-9

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