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Semin Liver Dis 2006; 26(3): 265-272
DOI: 10.1055/s-2006-947294
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Evolving Dilemmas and Management of Portopulmonary Hypertension

Michael J. Krowka1
  • 1Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
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Publication History

Publication Date:
19 July 2006 (online)

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ABSTRACT

Portopulmonary hypertension (POPH) is an uncommon but serious pulmonary vascular consequence of portal hypertension. Untreated, POPH results in right heart failure and death, regardless of the severity of portal hypertension. The existence of moderate to severe POPH has posed higher risk for orthotopic liver transplantation (OLT). New and evolving medical approaches may change the natural history of this disorder. Such approaches include administration of prostacyclins, endothelin receptor antagonists, and phosphodiesterase inhibitors. Administration may involve 24-hour continuous infusions, periodic inhaled, and oral routes. Liver transplantation in patients with moderate to severe POPH is problematic. Aside from patients being denied OLT specifically because of POPH, intraoperative death has occurred and unacceptable mortality during the transplant hospitalization has been reported. Finally, guidelines are evolving concerning which patients will benefit from the combination of evolving medical therapies and OLT. Whether the natural history of POPH can be dramatically changed remains an optimistic conjecture.

KEYWORDS

Liver transplantation - echocardiography - pulmonary hypertension

REFERENCES

  • 1 Krowka M J. Hepatopulmonary syndrome and portopulmonary hypertension: distinctions and dilemmas.  Hepatology. 1997;  25 1282-1284
    CrossrefPubMedGoogle Scholar
  • 2 Herve P, Lebrec D, Brenot F et al.. Pulmonary vascular disorders in portal hypertension.  Eur Respir J. 1998;  11 1153-1166
    CrossrefPubMedGoogle Scholar
  • 3 Rodriguez-Roisin R, Krowka M J, Herve P et al.. Pulmonary-hepatic vascular disorders: a task force report.  Eur Respir J. 2004;  24 861-880
    CrossrefPubMedGoogle Scholar
  • 4 Krowka M J, Frantz R P, McGoon M D et al.. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension.  Hepatology. 1999;  30 641-648
    CrossrefPubMedGoogle Scholar
  • 5 Edwards B S, Weir E K, Edwards W D et al.. Coexistent pulmonary and portal hypertension: morphologic and clinical features.  J Am Coll Cardiol. 1987;  10 1233-1288
    CrossrefPubMedGoogle Scholar
  • 6 Krowka M J, Edwards W D. The spectrum of pathology in portopulmonary hypertension.  Liver Transpl. 2000;  6 241-242
    CrossrefPubMedGoogle Scholar
  • 7 Hadengue A, Benhayoun M K, Lebrec D et al.. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics.  Gastroenterology. 1991;  100 520-528
    PubMedGoogle Scholar
  • 8 Robalino B D, Moodie D S. Association between primary pulmonary hypertension and portal hypertension: analysis of its pathophysiology and clinical, laboratory and hemodynamic manifestations.  J Am Coll Cardiol. 1991;  17 492-498
    CrossrefPubMedGoogle Scholar
  • 9 Kawut S M, Taichman D B, Alrya V N et al.. Hemodynamics and survival of patients with portopulmonary hypertension.  Liver Transpl. 2005;  11 1107-1111
    CrossrefPubMedGoogle Scholar
  • 10 Swanson K L, McGoon M D, Krowka M J. Survival in portopulmonary hypertension and orthotopic liver transplantation [abstract].  Liver Transpl. 2005;  11 C-71
    PubMedGoogle Scholar
  • 11 Simonneau G, Galie N, Rubin L J et al.. Clinical classification of pulmonary hypertension.  J Am Coll Cardiol. 2004;  43 5S-12S
    CrossrefPubMedGoogle Scholar
  • 12 Mantz Jr F A, Craige E. Portal axis thrombosis with spontaneous portacaval shunt and resultant cor pulmonale.  AMA Arch Pathol. 1951;  52 91-97
    PubMedGoogle Scholar
  • 13 Senior R M, Britton R C, Turino G M et al.. Pulmonary hypertension associated with cirrhosis of the liver and with portacaval shunts.  Circulation. 1968;  37 88-96
    CrossrefPubMedGoogle Scholar
  • 14 Lebrec D, Capron J P, Dhumeaux D, Benhamou J P. Pulmonary hypertension complicating portal hypertension.  Am Rev Respir Dis. 1979;  120 849-856
    PubMedGoogle Scholar
  • 15 Kuo P C, Plotkin J S, Johnson L B et al.. Distinctive clinical features of portopulmonary hypertension.  Chest. 1997;  112 980-986
    PubMedGoogle Scholar
  • 16 Hoeper M M, Rubin L J. Update in pulmonary hypertension 2005.  Am J Respir Crit Care Med. 2006;  173 499-503
    CrossrefPubMedGoogle Scholar
  • 17 Donovan C L, Marcovitz P A, Punch J D et al.. Two-dimensional and dobutamine stress echocardiography in the preoperative assessment of patients with end-stage liver disease prior to orthotopic liver transplantation.  Transplantation. 1996;  61 1180-1188
    PubMedGoogle Scholar
  • 18 Kim W R, Krowka M J, Plevak D J et al.. Accuracy of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplant candidates.  Liver Transpl. 2000;  6 453-458
    CrossrefPubMedGoogle Scholar
  • 19 Cotton C L, Gandhi S, Vaitkus P T et al.. Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates.  Liver Transpl. 2002;  8 1051-1054
    CrossrefPubMedGoogle Scholar
  • 20 Krowka M J, Swanson K L, Frantz R P et al.. Screening for portopulmonary hypertension and results of right heart catheterization [abstract].  Liver Transpl. 2005;  11 C-83
    PubMedGoogle Scholar
  • 21 Benjaminov F S, Prentice M, Sniderman K W et al.. Portopulmonary hypertension in decompensated cirrhosis and refractory ascites.  Gut. 2003;  52 1355-1362
    CrossrefPubMedGoogle Scholar
  • 22 Castro M, Krowka M J, Schroeder D R et al.. Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients.  Mayo Clin Proc. 1996;  71 543-551
    CrossrefPubMedGoogle Scholar
  • 23 Wiesner R, Edwards E, Freeman R et al.. Model for end-stage liver disease (MELD) and allocation of liver donors.  Gastroenterology. 2003;  124 91-96
    CrossrefPubMedGoogle Scholar
  • 24 Azoulay D, Castaing Y, Dennison A et al.. Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic circulatory state of the cirrhotic patient.  Hepatology. 1994;  19 129-132
    CrossrefPubMedGoogle Scholar
  • 25 Van der Linden P, Le Moine O, Ghysels M et al.. Pulmonary hypertension after transjugular intrahepatic portosystemic shunt effects on the right ventricle.  Hepatology. 1996;  23 982-987
    PubMedGoogle Scholar
  • 26 Murray K F, Carithers R L. AASLD practice guidelines: evaluation of the patients for liver transplantation.  Hepatology. 2005;  41 1407-1432
    CrossrefPubMedGoogle Scholar
  • 27 Kuo P C, Johnson L B, Plotkin J S et al.. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension.  Transplantation. 1997;  63 604-606
    CrossrefPubMedGoogle Scholar
  • 28 McLaughlin V V, Genthner R N, Panella M M et al.. Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension.  Ann Intern Med. 1999;  130 740-743
    PubMedGoogle Scholar
  • 29 Hoeper M M, Halank M, Marx C et al.. Bosentan for the treatment of portopulmonary hypertension.  Eur Respir J. 2005;  25 502-508
    CrossrefPubMedGoogle Scholar
  • 30 Plotkin J S, Kuo P C, Rubin L J et al.. Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension.  Transplantation. 1998;  65 457-459
    PubMedGoogle Scholar
  • 31 Tan H P, Markowitz J S, Montgomery R A et al.. Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.  Liver Transpl. 2001;  7 745-749
    CrossrefPubMedGoogle Scholar
  • 32 Kett D H, Acost R C, Campos M A et al.. Recurrent portopulmonary hypertension after liver transplantation: management with epoprostenol and resolution after retransplantation.  Liver Transpl. 2001;  7 645-648
    CrossrefPubMedGoogle Scholar
  • 33 Minder S, Fishler M, Muelihaupt B et al.. Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension.  Eur Respir J. 2004;  24 703-707
    CrossrefPubMedGoogle Scholar
  • 34 Clift P F, Bramhill S, Isaac J L. Successful treatment of severe portopulmonary hypertension after liver transplantation by bosentan.  Transplantation. 2004;  77 1774-1776
    PubMedGoogle Scholar
  • 35 Kuntzen C, Golberg V, Gerbes A L. Use of a mixed endothelin receptor antagonist in portopulmonary hypertension: a safe and effective therapy?.  Gastroenterology. 2005;  128 164-168
    CrossrefPubMedGoogle Scholar
  • 36 Molnar C, Alber H, Colleselli D et al.. Successful switch from inhaled iloprost to oral bosentan in portopulmonary hypertension associated with liver cirrhosis.  Wien Klin Wochenschr. 2004;  116 627-630
    CrossrefPubMedGoogle Scholar
  • 37 Kahler C M, Graziadei I, Wiedermann C J et al.. Novel use of sildenafil in the treatment of portopulmonary hypertension.  Wien Klin Wochenschr. 2000;  112 637-640
    PubMedGoogle Scholar
  • 38 Makisalo H, Koivusalo A, Vakkuri A et al.. Sildenafil for portopulmonary hypertension in a patient undergoing liver transplantation.  Liver Transpl. 2004;  10 945-950
    CrossrefPubMedGoogle Scholar
  • 39 Kao P N. Simvastatin treatment for pulmonary hypertension.  Chest. 2005;  127 1446-1452
    CrossrefPubMedGoogle Scholar
  • 40 Sulica R, Emre S, Poon M. Medical management of portopulmonary hypertension and right heart failure prior to living-related liver transplantation.  Congest Heart Fail. 2004;  10 192-194
    PubMedGoogle Scholar
  • 41 Henriksen J H, Gotz J P, Fuglsang S et al.. Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease.  Gut. 2003;  52 1511-1517
    CrossrefPubMedGoogle Scholar
  • 42 Provencher S, Herve P, Jais X et al.. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension.  Gastroenterology. 2006;  130 120-126
    CrossrefPubMedGoogle Scholar
  • 43 Krowka M J, Mandell M S, Ramsay M AE et al.. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database.  Liver Transpl. 2004;  10 174-182
    CrossrefPubMedGoogle Scholar
  • 44 Schott R, Chaouat A, Launoy A et al.. Improvement of pulmonary hypertension after liver transplantation.  Chest. 1999;  115 1748-1749
    CrossrefPubMedGoogle Scholar
  • 45 De Wolf A M, Gasior T, Kang Y. Pulmonary hypertension in a patient undergoing liver transplantation.  Transplant Proc. 1991;  23 2000-2001
    PubMedGoogle Scholar
  • 46 Krowka M J, Plevak D J, Findlay J Y et al.. Pulmonary hemodynamics and perioperative cardiopulmonary mortality in patients with portopulmonary hypertension undergoing liver transplantation.  Liver Transpl. 2000;  6 443-450
    CrossrefPubMedGoogle Scholar
  • 47 Ramsay M AE, Simpson B R, Nguyen A T et al.. Severe pulmonary hypertension in liver transplant candidates.  Liver Transpl Surg. 1997;  3 494-500
    CrossrefPubMedGoogle Scholar
  • 48 Starkel P, Vera A, Gunson B, Mutimer D. Outcome of liver transplantation for patients with pulmonary hypertension.  Liver Transpl. 2002;  8 382-388
    CrossrefPubMedGoogle Scholar
  • 49 Pirenne J, Verlede G, Nevens F et al.. Combined liver and heart-lung transplantation in liver transplant candidates with refractory portopulmonary hypertension.  Transplantation. 2002;  73 140-142
    PubMedGoogle Scholar
  • 50 Urashima Y, Tojimbara T, Nakajima I et al.. Living related liver transplantation for biliary atresia with portopulmonary hypertension.  Transplant Proc. 2004;  36 2237-2238
    CrossrefPubMedGoogle Scholar
  • 51 Kikuchi H, Ohkoohchi N, Orli T et al.. Living-related liver transplantation in patients with pulmonary vascular disease.  Transplant Proc. 2000;  32 2177-2178
    CrossrefPubMedGoogle Scholar
  • 52 Martinez-Palli G, Barbera J A, Taura P et al.. Severe portopulmonary hypertension after liver transplantation in a patient with preexisting hepatopulmonary syndrome.  J Hepatol. 1999;  31 1075-1079
    CrossrefPubMedGoogle Scholar
  • 53 Kaspar M D, Ramsay M A, Shuey Jr C B et al.. Severe pulmonary hypertension and amelioration of hepatopulmonary syndrome after liver transplantation.  Liver Transpl Surg. 1998;  4 177-179
    CrossrefPubMedGoogle Scholar
  • 54 Aucejo F, Miller C, Vogt D et al.. Portopulmonary hypertension following liver transplantation in patients with antecedent hepatopulmonary syndrome.  Liver Transpl. 2006;  , In press
    PubMedGoogle Scholar
  • 55 Mandell M S, Groves B M, Duke J. Progressive plexogenic pulmonary hypertension following liver transplantation.  Transplantation. 1995;  59 1488-1490
    PubMedGoogle Scholar
  • 56 Koneru B, Fisher A, Wilson D J et al.. De novo diagnosis of portopulmonary hypertension following liver transplantation.  Am J Transplant. 2002;  2 883-886
    CrossrefPubMedGoogle Scholar
  • 57 Mal H, Burgiere O, Durand F et al.. Pulmonary hypertension following hepatopulmonary syndrome.  J Hepatol. 1999;  31 360-364
    CrossrefPubMedGoogle Scholar
  • 58 Shah T, Isaac J, Adams D et al.. Development of hepatopulmonary syndrome and portopulmonary hypertension in a paediatric liver transplant recipient.  Pediatr Transplant. 2005;  9 127-131
    CrossrefPubMedGoogle Scholar
  • 59 Jones F D, Kuo P C, Johnson L B et al.. The coexistence of portopulmonary hypertension and hepatopulmonary syndrome.  Anesthesiology. 1999;  90 626-629
    PubMedGoogle Scholar
  • 60 Tasaka S, Kanazawa M, Nakamura H et al.. An autopsied case of primary pulmonary hypertension complicated by hepatopulmonary syndrome.  Nihon Kyobu Shikkan Gakkai Zasshi. 1995;  33 90-94
    PubMedGoogle Scholar
  • 61 Castro P F, Bourge R C, McGiffin D C. Intrapulmonary shunting in primary pulmonary hypertension: an observation in two patients treated with epoprostenol sodium.  Chest. 1998;  114 334-336
    PubMedGoogle Scholar
  • 62 Cool C D, Stewart J S, Werahera P et al.. Three-dimensional reconstruction of pulmonary arteries in plexiform pulmonary hypertension.  Am J Pathol. 1999;  155 411-419
    CrossrefPubMedGoogle Scholar
  • 63 Sussman N, Frost A, Kaza V et al.. Successful liver transplantation following treatment of portopulmonary hypertension [abstract].  Hepatology. 2005;  42 327A
    PubMedGoogle Scholar
  • 64 Schermuly R T, Dony E, Ghofrani H A et al.. Reversal of experimental pulmonary hypertension by PDGF inhibition.  J Clin Invest. 2005;  115 2811-2821
    CrossrefPubMedGoogle Scholar

Michael J KrowkaM.D. 

Professor of Medicine, Vice-Chair, Division of Pulmonary and Critical Care, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine

200 First Street SW, Rochester, MN 55905

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