Clinical Pharmacology of Portal Hypertension

Gastroenterology Clinics of North America

Volumn 39, Issue 3, 2010, Pages 681-695

  Miñano, Cecilia ^a,b   Garcia Tsao, Guadalupe ^a,b  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

Author keywords

Cirrhosis; Hepatic venous pressure gradient; Portal hypertension; Portal pressure; Variceal hemorrhage; Varices

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; ATENOLOL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CARVEDILOL; CEFTRIAXONE; CLONIDINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; GLYCERYL TRINITRATE; IRBESARTAN; ISOSORBIDE MONONITRATE; METOPROLOL; NADOLOL; NCX 1000; NITRIC ACID DERIVATIVE; NORFLOXACIN; OCTREOTIDE; PLACEBO; PRAZOSIN; PROPRANOLOL; SIMVASTATIN; SOMATOSTATIN DERIVATIVE; TERLIPRESSIN; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID DERIVATIVE; VAPREOTIDE; VASOCONSTRICTOR AGENT; VASODILATOR AGENT; VASOPRESSIN DERIVATIVE;

ABDOMINAL PAIN; ASCITES; BLOOD PRESSURE MEASUREMENT; BUDD CHIARI SYNDROME; CLINICAL TRIAL; COLLATERAL CIRCULATION; CONTINUOUS INFUSION; CREATININE CLEARANCE; DIZZINESS; DRUG DOSE INCREASE; DRUG HALF LIFE; DRUG METABOLISM; DRUG RESPONSE; DRUG WITHDRAWAL; DYSPNEA; EDEMA; ESOPHAGUS VARICES; ESOPHAGUS VARICES BLEEDING; EVENING DOSAGE; FATIGUE; FLUID RETENTION; GANGRENE; GASTROINTESTINAL HEMORRHAGE; HEART HEMODYNAMICS; HEART MUSCLE ISCHEMIA; HUMAN; HYPERGLYCEMIA; HYPERTENSION; LIVER CIRRHOSIS; MEAN ARTERIAL PRESSURE; NAUSEA; NONHUMAN; PATHOPHYSIOLOGY; PERIPHERAL ISCHEMIA; PORTAL HYPERTENSION; PORTAL VEIN BLOOD FLOW; PORTAL VEIN BLOOD PRESSURE; PRESSURE GRADIENT; PRIMARY PREVENTION; REVIEW; SECONDARY PREVENTION; SIDE EFFECT; SODIUM RETENTION; SPLENIC VEIN; UNSPECIFIED SIDE EFFECT; VASCULAR RESISTANCE; VASOCONSTRICTION; VASODILATATION; VEIN THROMBOSIS; VOMITING;

ADRENERGIC BETA-ANTAGONISTS; FIBROSIS; HEMORRHAGE; HUMANS; HYPERTENSION, PORTAL; LIVER; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SOMATOSTATIN; VARICOSE VEINS; VASOCONSTRICTOR AGENTS; VASODILATOR AGENTS; VASOPRESSINS;

EID: 77957907233     PISSN: 08898553     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.gtc.2010.08.015     Document Type: Review

References (88)

1. Groszmann R.J., Garcia-Tsao G., Bosch J., et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005, 353:2254-2261.
2. 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.
3. Bruix J., Castells A., Bosch J., et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients. Prognostic value of preoperative portal pressure. Gastroenterology 1996, 111:1018-1022.
4. Ripoll C., Groszmann R.J., Garcia-Tsao G., et al. Hepatic venous pressure gradient predicts development of hepatocellular carcinoma independently of severity of cirrhosis. J Hepatol 2009, 50:923-928.
5. Bhathal P.S., Grossman H.J. Reduction of the increased portal vascular resistance of the isolated perfused cirrhotic rat liver by vasodilators. J Hepatol 1985, 1:325-337.
6. 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.
7. Wiest R., Groszmann R.J. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 2002, 35:478-491.
8. Iwakiri Y., Groszmann R.J. Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007, 46:927-934.
9. Sikuler E., Groszmann R.J. Interaction of flow and resistance in maintenance of portal hypertension in a rat model. Am J Physiol 1986, 250:G205-G212.
10. Fernandez M., Vizzutti F., Garcia-Pagan J.C., et al. Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice. Gastroenterology 2004, 126:886-894.
11. Groszmann R.J., Wongcharatrawee S. The hepatic venous pressure gradient: anything worth doing should be done right. Hepatology 2004, 39:280-283.
12. Feu F., Bordas J.M., Luca A., et al. Reduction of variceal pressure by propranolol: comparison of the effects on portal pressure and azygos blood flow in patients with cirrhosis. Hepatology 1993, 18:1082-1089.
13. Abraldes J.G., Tarantino I., Turnes J., et al. Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis. Hepatology 2003, 37:902-908.
14. D'Amico G., Garcia-Pagan J.C., Luca A., et al. HVPG reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 2006, 131:1611-1624.
15. Villanueva C., Aracil C., Colomo A., et al. Acute hemodynamic response to beta-blockers and prediction of long-term outcome in primary prophylaxis of variceal bleeding. Gastroenterology 2009, 137:119-128.
16. La Mura V., Abraldes J.G., Raffa S., et al. Prognostic value of acute hemodynamic response to i.v. propranolol in patients with cirrhosis and portal hypertension. J Hepatol 2009, 51:279-287.
17. Garcia-Tsao G., Bosch J., Groszmann R.J. Portal hypertension and variceal bleeding-unresolved issues. Summary of an American Association for the Study of Liver Diseases and European Association for the Study of the Liver single-topic conference. Hepatology 2008, 47:1764-1772.
18. Fernandez M., Mejias M., Angermayr B., et al. Inhibition of VEGF receptor-2 decreases the development of hyperdynamic splanchnic circulation and portal-systemic collateral vessels in portal hypertensive rats. J Hepatol 2005, 43:98-103.
19. Mills P.R., Rae A.P., Farah D.A., et al. Comparison of three adrenoceptor blocking agents in patients with cirrhosis and portal hypertension. Gut 1984, 25:73-78.
20. Garcia-Tsao G., Grace N., Groszmann R.J., et al. Short term effects of propranolol on portal venous pressure. Hepatology 1986, 6:101-106.
21. Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: varices and variceal hemorrhage, ascites and spontaneous bacterial peritonitis. Gastroenterology 2001, 120:726-748.
22. Groszmann R.J., Bosch J., Grace N., et al. Hemodynamic events in a prospective randomized trial of propranolol vs placebo in the prevention of the first variceal hemorrhage. Gastroenterology 1990, 99(5):1401-1407.
23. 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.
24. Banares R., Moitinho E., Matilla A., et al. Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis. Hepatology 2002, 36:1367-1373.
25. Turnes J., Garcia-Pagan J.C., Abraldes J.G., et al. Pharmacological reduction of portal pressure and long-term risk of first variceal bleeding in patients with cirrhosis. Am J Gastroenterol 2006, 101:506-512.
26. Sharma P., Kumar A., Sharma B.C., et al. Early identification of haemodynamic response to pharmacotherapy is essential for primary prophylaxis of variceal bleeding in patients with 'high-risk' varices. Aliment Pharmacol Ther 2009, 30:48-60.
27. Merkel C., Bolognesi M., Berzigotti A., et al. Clinical significance of worsening portal hypertension during long-term medical treatment in patients with cirrhosis who had been classified as early good-responders on haemodynamic criteria. J Hepatol 2010, 52:45-53.
28. Feu F., Garcia-Pagan J.C., 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.
29. Villanueva C., Balanzo J., Novella M.T., et al. Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding. N Engl J Med 1996, 334:1624-1629.
30. McCormick P.A., Patch D., Greenslade L., et al. Clinical vs hemodynamic response to drugs in portal hypertension. J Hepatol 1998, 28:1015-1019.
31. 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.
32. Patch D., Goulis J., Gerunda G., et al. A randomized controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis. Gastroenterology 2002, 123:1013-1019.
33. Villanueva C., Lopez-Balaguer J.M., Aracil C., et al. Maintenance of hemodynamic response to treatment for portal hypertension and influence on complications of cirrhosis. J Hepatol 2004, 40:757-765.
34. Garcia-Pagan J.C., Villanueva C., Albillos A., et al. Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of variceal rebleeding: a multicenter randomized controlled trial. Gut 2009, 58:1144-1150.
35. Villanueva C., Aracil C., Colomo A., et al. Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy. Aliment Pharmacol Ther 2009, 29:397-408.
36. Escorsell A., Bordas J.M., Castaneda B., et al. Predictive value of the variceal pressure response to continued pharmacological therapy in patients with cirrhosis and portal hypertension. Hepatology 2000, 31:1061-1067.
37. Bureau C., Peron J.M., Alric L., et al. ″ A La Carte″ treatment of portal hypertension: adapting medical therapy to hemodynamic response for the prevention of bleeding. Hepatology 2002, 36:1361-1366.
38. Kroeger R.J., Groszmann R.J. Increased portal venous resistance hinders portal pressure reduction during the administration of beta-adrenergic blocking agents in a portal hypertensive model. Hepatology 1985, 5:97-101.
39. Garcia-Tsao G., Sanyal A.J., Grace N.D., et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007, 46:922-938.
40. Longacre A.V., Imaeda A., Garcia-Tsao G., et al. A pilot project examining the predicted preferences of patients and physicians in the primary prophylaxis of variceal hemorrhage. Hepatology 2008, 47:169-176.
41. D'Amico G., Pagliaro L., Bosch J. Pharmacological treatment of portal hypertension: an evidence-based approach. Semin Liver Dis 1999, 19:475-505.
42. 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.
43. Wiest R., Tsai M.H., Groszmann R.J. Octreotide potentiates PKC-dependent vasoconstrictors in portal-hypertensive and control rats. Gastroenterology 2000, 120:975-983.
44. Cirera I., Feu F., Luca A., et al. Effects of bolus injections and continuous infusions of somatostatin and placebo in patients with cirrhosis and portal hypertension. A double-blind hemodynamic investigation. Hepatology 1995, 22:106-111.
45. Escorsell A., Bandi J.C., Andreu V., et al. Desensitization to the effects of intravenous octreotide in cirrhotic patients with portal hypertension. Gastroenterology 2001, 120:161-169.
46. Buonamico P., Sabba C., Garcia-Tsao G., et al. Octreotide blunts post-prandial splanchnic hyperemia in cirrhotic patients: a double-blind randomized echo-Doppler study. Hepatology 1995, 21:134-139.
47. Spahr L., Giostra E., Frossard J.L., et al. A 3-month course of long-acting repeatable octreotide (sandostatin LAR) improves portal hypertension in patients with cirrhosis: a randomized controlled study. Am J Gastroenterol 2007, 102:1397-1405.
48. 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.
49. Escorsell A., Bordas J.M., Ruiz-del-Arbol L., et al. Randomized controlled trial of sclerotherapy versus somatostatin infusion in the prevention of early rebleeding following acute variceal hemorrhage in patients with cirrhosis. J Hepatol 1998, 29:779-788.
50. Blei A.T., Garcia-Tsao G., Groszmann R.J., et al. Hemodynamic evaluation of isosorbide dinitrate in alcoholic cirrhosis: pharmacokinetic-hemodynamic interactions. Gastroenterology 1987, 93:576-583.
51. Schepke M., Werner E., Biecker E., et al. Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Gastroenterology 2001, 121:389-395.
52. Albillos A., Lledo J.L., Banares R., et al. Hemodynamic effects of a-adrenergic blockade with prazosin in cirrhotic patients with portal hypertension. Hepatology 1994, 20:611-617.
53. Albillos A., Lledo J.L., Rossi I., et al. Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function. Gastroenterology 1995, 109:1257-1265.
54. Garcia-Pagan J.C., Villanueva C., Vila M.C., et al. Isosorbide mononitrate in the prevention of first variceal bleed in patients who cannot receive beta-blockers. Gastroenterology 2001, 121:908-914.
55. Tandon P., Abraldes J.G., Berzigotti A., et al. Renin-angiotensin-aldosterone inhibitors in the reduction of portal pressure: a systematic review and meta-analysis. J Hepatol 2010, 53:273-282.
56. Berzigotti A., Bellot P., De Gottardi A., et al. NCX-1000, a nitric oxide-releasing derivative of UDCA, does not decrease portal pressure in patients with cirrhosis: results of a randomized, double-blind, dose-escalating study. Am J Gastroenterol 2010, 105:1094-1101.
57. Abraldes J.G., Albillos A., Banares R., et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology 2009, 136:1651-1658.
58. Groszmann R.J., Kravetz D., Bosch J., et al. Nitroglycerin improves the hemodynamic response to vasopressin in portal hypertension. Hepatology 1982, 2:757-762.
59. Albillos A., Garcia-Pagan J.C., Iborra J., et al. Propranolol plus prazosin compared with propranolol plus isosorbide-5-mononitrate in the treatment of portal hypertension. Gastroenterology 1998, 115:116-123.
60. Stanley A.J., Therapondos G., Helmy A., et al. Acute and chronic haemodynamic and renal effects of carvedilol in patients with cirrhosis. J Hepatol 1999, 30:479-484.
61. Bruha R., Vitek L., Petrtyl J., et al. Effect of carvedilol on portal hypertension depends on the degree of endothelial activation and inflammatory changes. Scand J Gastroenterol 2006, 41:1454-1463.
62. 1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis. Hepatology 1999, 30:79-83.
63. Kovalak M., Lake J., Mattek N., et al. Endoscopic screening for varices in cirrhotic patients: data from a national endoscopic database. Gastrointest Endosc 2007, 65:82-88.
64. Merli M., Nicolini G., Angeloni S., et al. Incidence and natural history of small esophageal varices in cirrhotic patients. J Hepatol 2003, 38:266-272.
65. 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.
66. Abraldes J.G., 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.
67. Augustin S., Muntaner L., Altamirano J.T., et al. Predicting early mortality after acute variceal hemorrhage based on classification and regression tree analysis. Clin Gastroenterol Hepatol 2009, 7:1347-1354.
68. Bosch J., Garcia-Pagan J.C. Prevention of variceal rebleeding. Lancet 2003, 361:952-954.
69. Garcia-Pagan J.C., Morillas R., Banares R., et al. Propranolol plus placebo versus propranolol plus isosorbide-5-mononitrate in the prevention of a first variceal bleed: a double-blind RCT. Hepatology 2003, 37:1260-1266.
70. Gluud L.L., Klingenberg S., Nikolova D., et al. Banding ligation versus beta-blockers as primary prophylaxis in esophageal varices: systematic review of randomized trials. Am J Gastroenterol 2007, 102:2842-2848.
71. Bosch J., Berzigotti A., Garcia-Pagan J.C., et al. The management of portal hypertension: rational basis, available treatments and future options. J Hepatol 2008, 48(Suppl 1):S68-S92.
72. Tripathi D., Ferguson J.W., Kochar N., et al. Randomized controlled trial of carvedilol versus variceal band ligation for the prevention of the first variceal bleed. Hepatology 2009, 50:825-833.
73. 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.
74. Ioannou G., Doust J., Rockey D.C. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev 2001, (1). CD002147.
75. 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.
76. Bernard B., Grange J.D., Khac E.N., et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 1999, 29:1655-1661.
77. Hou M.C., Lin H.C., Liu T.T., et al. Antibiotic prophylaxis after endoscopic therapy prevents rebleeding in acute variceal hemorrhage: a randomized trial. Hepatology 2004, 39:746-753.
78. Fernandez J., Ruiz d A., Gomez C., et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology 2006, 131:1049-1056.
79. Bosch J., Thabut D., Bendtsen F., et al. Recombinant factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis: a randomized, double-blind trial. Gastroenterology 2004, 127:1123-1130.
80. Bosch J., Thabut D., Albillos A., et al. Recombinant factor VIIa for variceal bleeding in patients with advanced cirrhosis: a randomized, controlled trial. Hepatology 2008, 47:1604-1614.
81. Gonzalez R., Zamora J., Gomez-Camarero J., et al. Meta-analysis: combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis. Ann Intern Med 2008, 149:109-122.
82. Lo G.H., Chen W.C., Lin C.K., et al. Improved survival in patients receiving medical therapy as compared with banding ligation for the prevention of esophageal variceal rebleeding. Hepatology 2008, 48:580-587.
83. Lo G.H., Lai K.H., Cheng J.S., 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.
84. de la Pena J., Brullet E., Sanchez-Hernandez E., et al. Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: a multicenter trial. Hepatology 2005, 41:572-578.
85. Lo G.H., Chen W.C., Chen M.H., et al. A prospective, randomized trial of endoscopic variceal ligation versus nadolol and isosorbide mononitrate for the prevention of esophageal variceal rebleeding. Gastroenterology 2002, 123:728-734.
86. Romero G., Kravetz D., Argonz J., et al. Comparative study between nadolol and 5-isosorbide mononitrate vs. endoscopic band ligation plus sclerotherapy in the prevention of variceal rebleeding in cirrhotic patients: a randomized controlled trial. Aliment Pharmacol Ther 2006, 24:601-611.
87. Lo G.H., Chen W.C., Chan H.H., et al. A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding. J Gastroenterol Hepatol 2009, 24:982-987.
88. Kumar A., Jha S.K., Sharma P., et al. Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence. Gastroenterology 2009, 137:892-901.