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Expert Opinion on Pharmacotherapy Volume 10, 2009 - Issue 3
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Review

Pathophysiologic basis for the medical management of portal hypertension

Fred F Poordad Cedars-Sinai Medical Center, Center for Liver Disease and Transplantation, 8635 W. Third Street, Suite 1060W, Los Angeles, CA 90048, USA, +1 310 423 1971; +1 310 423 1693; [email protected]
, MD,
Samuel H Sigal Weill Cornell Medical College, New York, NY, USA
, MD &
Robert S Brown Jr Columbia University Medical Center, New York, NY, USA
, MD MPH
Pages 453-467 | Published online: 04 Feb 2009

Bibliography

  • Bosch J. Vascular deterioration in cirrhosis: the big picture. J Clin Gastroenterol 2007;41(10 Suppl 3):S247-53
  • Bosch J, Navasa M, Kravetz D, et al. Diagnosis and evaluation of portal hypertension. Z Gastroenterol 1988;26(Suppl 2):8-14
  • Groszmann RJ, Garcia-Tsao G, Bosch J, et al. Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. N Engl J Med 2005;353(21):2254-61
  • Harmanci O, Bayraktar Y. Portal hypertension due to portal venous thrombosis: etiology, clinical outcomes. World J Gastroenterol 2007;13(18):2535-40
  • Harmanci O, Bayraktar Y. Clinical characteristics of idiopathic portal hypertension. World J Gastroenterol 2007;13(13):1906-11
  • Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol 2007;46(5):927-34
  • Wiest R, Groszmann RJ. The paradox of nitric oxide in cirrhosis and portal hypertension: too much, not enough. Hepatology 2002;35(2):478-91
  • Gupta TK, Toruner M, Groszmann RJ. Intrahepatic modulation of portal pressure and its role in portal hypertension. Role of nitric oxide. Digestion 1998;59(4):413-5
  • Shah V, Toruner M, Haddad F, et al. Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat. Gastroenterology 1999;117(5):1222-8
  • Graupera M, Garcia-Pagan JC, Pares M, et al. Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers. J Hepatol 2003;39(4):515-21
  • Rockey DC. Vascular mediators in the injured liver. Hepatology 2003;37(1):4-12
  • Zipprich A. Hemodynamics in the isolated cirrhotic liver. J Clin Gastroenterol 2007;41(10 Suppl 3):S254-8
  • 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(1):98-103
  • 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(5):1210-8
  • Dagher L, Moore K. The hepatorenal syndrome. Gut 2001;49(5):729-37
  • Tox U, Steffen HM. Impact of inhibitors of the Renin-Angiotensin-aldosterone system on liver fibrosis and portal hypertension. Curr Med Chem 2006;13(30):3649-61
  • Warner FJ, Lubel JS, McCaughan GW, Angus PW. Liver fibrosis: a balance of ACEs? Clin Sci (Lond) 2007;113(3):109-18
  • Baveja R, Kresge N, Ashburn JH, et al. Potentiated hepatic microcirculatory response to endothelin-1 during polymicrobial sepsis. Shock 2002;18(5):415-22
  • Eum HA, Park SW, Lee SM. Role of nitric oxide in the expression of hepatic vascular stress genes in response to sepsis. Nitric Oxide 2007;17(3-4):126-33
  • Han X, Fink MP, Yang R, Delude RL. Increased iNOS activity is essential for intestinal epithelial tight junction dysfunction in endotoxemic mice. Shock 2004;21(3):261-70
  • Batkai S, Mukhopadhyay P, Harvey-White J, et al. Endocannabinoids acting at CB1 receptors mediate the cardiac contractile dysfunction in vivo in cirrhotic rats. Am J Physiol Heart Circ Physiol 2007;293(3):H1689-95
  • Ros J, Claria J, To-Figueras J, et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology 2002;122(1):85-93
  • Toghill P. The syndromes of splenic dysfunction: a clinical overview. In: Bowdler AJ, editor, The spleen. Structure, function and clinical significance. Chapman & Hall, New York, NY; 1990. p. 209-32
  • Cales P, Desmorat H, Vinel JP, et al. Incidence of large oesophageal varices in patients with cirrhosis: application to prophylaxis of first bleeding. Gut 1990;31(11):1298-302
  • Christensen E, Fauerholdt L, Schlichting P, et al. Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone. Gastroenterology 1981;81(5):944-52
  • Albillos A. Preventing first variceal hemorrhage in cirrhosis. J Clin Gastroenterol 2007;41(10 Suppl 3):S305-11
  • Samonakis DN, Triantos CK, Thalheimer U, et al. Management of portal hypertension. Postgrad Med J 2004;80(949):634-41
  • De Franchis R. 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(15):983-9
  • Sandhu BS, Sanyal AJ. Management of ascites in cirrhosis. Clin Liver Dis 2005;9(4):715-32, viii
  • Kuiper JJ, De Man RA, Van Buuren HR. Review article: Management of ascites and associated complications in patients with cirrhosis. Aliment Pharmacol Ther 2007;26(Suppl 2):183-93
  • Kuiper JJ, Van Buuren HR, De Man RA. Ascites in cirrhosis: a review of management and complications. Neth J Med 2007;65(8):283-8
  • Vivas S, Rodriguez M, Palacio MA, et al. Presence of bacterial infection in bleeding cirrhotic patients is independently associated with early mortality and failure to control bleeding. Dig Dis Sci 2001;46(12):2752-7
  • Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology 2007;133(3):818-24
  • 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(1):164-76
  • Wadei HM, Mai ML, Ahsan N, Gonwa TA. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol 2006;1(5):1066-79
  • Gines A, Escorsell A, Gines P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology 1993;105(1):229-36
  • Bichet DG, Van Putten VJ, Schrier RW. Potential role of increased sympathetic activity in impaired sodium and water excretion in cirrhosis. N Engl J Med 1982;307(25):1552-7
  • Henriksen JH, Ring-Larsen H. Hepatorenal disorders: role of the sympathetic nervous system. Semin Liver Dis 1994;14(1):35-43
  • Cordoba J, Minguez B. Hepatic encephalopathy. Semin Liver Dis 2008;28(1):70-80
  • Heidelbaugh JJ, Sherbondy M. Cirrhosis and chronic liver failure: part II. Complications and treatment. Am Fam Physician 2006;74(5):767-76
  • Addolorato G, Leggio L, Ferrulli A, et al. Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study. Lancet 2007;370(9603):1915-22
  • Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351(15):1521-31
  • Roberts S, Gordon A, McLean C, et al. Effect of sustained viral response on hepatic venous pressure gradient in hepatitis C-related cirrhosis. Clin Gastroenterol Hepatol 2007;5(8):932-7
  • Akriviadis E, Botla R, Briggs W, et al. Pentoxifylline improves short-term survival in severe acute alcoholic hepatitis: a double-blind, placebo-controlled trial. Gastroenterology 2000;119(6):1637-48
  • Austin AS, Mahida YR, Clarke D, et al. A pilot study to investigate the use of oxpentifylline (pentoxifylline) and thalidomide in portal hypertension secondary to alcoholic cirrhosis. Aliment Pharmacol Ther 2004;19(1):79-88
  • Albillos A, Lledo JL, Rossi I, et al. Continuous prazosin administration in cirrhotic patients: effects on portal hemodynamics and on liver and renal function. Gastroenterology 1995;109(4):1257-65
  • Evangelista ML, Amadori S, Stasi R. Biologic aspects of thrombopoietin and the development of novel thrombopoietic agents for clinical use. Curr Drug Discov Technol 2007;4(3):162-73
  • Rios R, Sangro B, Herrero I, et al. The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am J Gastroenterol 2005;100(6):1311-6
  • McHutchison JG, Dusheiko G, Shiffman ML, et al. Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C. N Engl J Med 2007;357(22):2227-36
  • Merkel C, Marin R, Angeli P, et al. A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis. Gastroenterology 2004;127(2):476-84
  • Reichen J. Liver function and pharmacological considerations in pathogenesis and treatment of portal hypertension. Hepatology 1990;11(6):1066-78
  • Poynard T, Cales P, Pasta L, et al. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of data and prognostic factors in 589 patients from four randomized clinical trials. Franco-Italian Multicenter Study Group. N Engl J Med 1991;324(22):1532-8
  • Abraczinskas DR, Ookubo R, Grace ND, et al. Propranolol for the prevention of first esophageal variceal hemorrhage: a lifetime commitment? Hepatology 2001;34(6):1096-102
  • Cales P, Oberti F, Payen JL, et al. Lack of effect of propranolol in the prevention of large oesophageal varices in patients with cirrhosis: a randomized trial. French-Speaking Club for the Study of Portal Hypertension. Eur J Gastroenterol Hepatol 1999;11(7):741-5
  • Abecasis R, Kravetz D, Fassio E, et al. Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study. Hepatology 2003;37(2):359-65
  • Albillos A, Banares R, Gonzalez M, et al. Value of the hepatic venous pressure gradient to monitor drug therapy for portal hypertension: a meta-analysis. Am J Gastroenterol 2007;102(5):1116-26
  • D'Amico G, Garcia-Pagan JC, Luca A, Bosch J. Hepatic vein pressure gradient reduction and prevention of variceal bleeding in cirrhosis: a systematic review. Gastroenterology 2006;131(5):1611-24
  • Lin HC, Yang YY, Hou MC, et al. Acute administration of carvedilol is more effective than propranolol plus isosorbide-5-mononitrate in the reduction of portal pressure in patients with viral cirrhosis. Am J Gastroenterol 2004;99(10):1953-8
  • Thalheimer U, Triantos CK, Samonakis DN, et al. Infection, coagulation, and variceal bleeding in cirrhosis. Gut 2005;54(4):556-63
  • Jun CH, Park CH, Lee WS, et al. Antibiotic prophylaxis using third generation cephalosporins can reduce the risk of early rebleeding in the first acute gastroesophageal variceal hemorrhage: a prospective randomized study. J Korean Med Sci 2006;21(5):883-90
  • Bernard B, Grange JD, Khac EN, et al. Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Hepatology 1999;29(6):1655-61
  • Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database Syst Rev 2002;2:CD002907
  • Bendtsen F, Krag A, Moller S. Treatment of acute variceal bleeding. Dig Liver Dis 2008;40(5):328-36
  • Ioannou G, Doust J, Rockey DC. Terlipressin for acute esophageal variceal hemorrhage. Cochrane Database Syst Rev 2003;1:CD002147
  • Romero G, Kravetz D, Argonz J, et al. Terlipressin is more effective in decreasing variceal pressure than portal pressure in cirrhotic patients. J Hepatol 2000;32(3):419-25
  • Yang JF, Wu XJ, Li JS, et al. Effect of somatostatin versus octreotide on portal haemodynamics in patients with cirrhosis and portal hypertension. Eur J Gastroenterol Hepatol 2005;17(1):53-7
  • Morales GF, Pereira Lima JC, Hornos AP, et al. Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial. Hepatogastroenterology 2007;54(73):195-200
  • Cales P, Masliah C, Bernard B, et al. Early administration of vapreotide for variceal bleeding in patients with cirrhosis. N Engl J Med 2001;344(1):23-8
  • Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006;355(20):2099-112
  • Gines P. Vaptans: a promising therapy in the management of advanced cirrhosis. J Hepatol 2007;46(6):1150-2
  • Bernardi M, Laffi G, Salvagnini M, et al. Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content. Liver 1993;13(3):156-62
  • Soares-Weiser K, Brezis M, Tur-Kaspa R, et al. Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials. Scand J Gastroenterol 2003;38(2):193-200
  • Rasaratnam B, Kaye D, Jennings G, et al. The effect of selective intestinal decontamination on the hyperdynamic circulatory state in cirrhosis. A randomized trial. Ann Intern Med 2003;139(3):186-93
  • Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341(6):403-9
  • Ghassemi S, Garcia-Tsao G. Prevention and treatment of infections in patients with cirrhosis. Best Pract Res Clin Gastroenterol 2007;21(1):77-93
  • 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(3):830-5
  • Solanki P, Chawla A, Garg R, et al. Beneficial effects of terlipressin in hepatorenal syndrome: a prospective, randomized placebo-controlled clinical trial. J Gastroenterol Hepatol 2003;18(2):152-6
  • 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(10):1535-40
  • 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(4 Pt 1):941-8
  • 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(5):1360-8
  • Esrailian E, Pantangco ER, Kyulo NL, et al. Octreotide/Midodrine therapy significantly improves renal function and 30-day survival in patients with type 1 hepatorenal syndrome. Dig Dis Sci 2007;52(3):742-8
  • Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology 2004;40(1):55-64
  • Lawrence KR, Klee JA. Rifaximin for the treatment of hepatic encephalopathy. Pharmacotherapy 2008;28(8):1019-32
  • Koconis KG, Singh H, Soares G. Partial splenic embolization in the treatment of patients with portal hypertension: a review of the english language literature. J Vasc Interv Radiol 2007;18(4):463-81
  • Laine L, Cook D. Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis. Ann Intern Med 1995;123(4):280-7
  • Sakai T, Shiraki K, Inoue H, et al. Complications of partial splenic embolization in cirrhotic patients. Dig Dis Sci 2002;47(2):388-91
  • Singh P, Pooran N, Indaram A, Bank S. Combined ligation and sclerotherapy versus ligation alone for secondary prophylaxis of esophageal variceal bleeding: a meta-analysis. Am J Gastroenterol 2002;97(3):623-9
  • Klupp J, Kohler S, Pascher A, Neuhaus P. Liver transplantation as ultimate tool to treat portal hypertension. Dig Dis 2005;23(1):65-71
  • Gonzalo T, Beljaars L, Van De Bovenkamp M, et al. Local inhibition of liver fibrosis by specific delivery of a platelet-derived growth factor kinase inhibitor to hepatic stellate cells. J Pharmacol Exp Ther 2007;321(3):856-65
  • Tu CT, Guo JS, Wang M, Wang JY. Antifibrotic activity of rofecoxib in vivo is associated with reduced portal hypertension in rats with carbon tetrachloride-induced liver injury. J Gastroenterol Hepatol 2007;22(6):877-84
  • Matei V, Rodriguez-Vilarrupla A, Deulofeu R, et al. The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis. Hepatology 2006;44(1):44-52
  • Trebicka J, Hennenberg M, Laleman W, et al. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology 2007;46(1):242-53
  • Laleman W, Van Landeghem L, Van Der Elst I, et al. Nitroflurbiprofen, a nitric oxide-releasing cyclooxygenase inhibitor, improves cirrhotic portal hypertension in rats. Gastroenterology 2007;132(2):709-19
  • Fernandez M, Mejias M, Garcia-Pras E, et al. Reversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats. Hepatology 2007;46(4):1208-17
  • Angermayr B, Fernandez M, Mejias M, et al. NAD(P)H oxidase modulates angiogenesis and the development of portosystemic collaterals and splanchnic hyperaemia in portal hypertensive rats. Gut 2007;56(4):560-4

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