Current Gastroenterology Reports

, Volume 13, Issue 1, pp 34–39 | Cite as

Pulmonary Complications of Cirrhosis

  • Rajan Kochar
  • Moises I. Nevah Rubin
  • Michael B. FallonEmail author


Pulmonary vascular complications of liver disease comprise two distinct clinical entities: hepatopulmonary syndrome (HPS—microvascular dilatation and angiogenesis) and portopulmonary hypertension (POPH—vasoconstriction and remodeling in resistance vessels). These complications occur in similar pathophysiologic environments and may share pathogenic mechanisms. HPS is found in 15% to 30% of patients with cirrhosis and its presence increases mortality and the risks of liver transplantation, particularly when hypoxemia is present. Contrast echocardiography and arterial blood gas analysis are required to establish the diagnosis. No medical therapies are available, although liver transplantation is effective in reversing the syndrome. POPH is found in 4% to 8% of patients undergoing liver transplantation evaluation, and the presence of moderate to severe disease significantly increases perioperative transplant mortality. Transthoracic echocardiography is recommended for screening and right-heart catheterization is required to establish the diagnosis. Medical therapies are increasingly effective in improving pulmonary vascular hemodynamics in POPH and may result in better perioperative outcomes.


Hepatopulmonary syndrome Portopulmonary hypertension Liver transplantation Pulmonary hypertension Intrapulmonary vasodilation Intrapulmonary shunting Pulmonary vascular complications of liver disease Contrast echocardiography 



No potential conflict of interest relevant to this article was reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Lange PA, Stoller JK: The hepatopulmonary syndrome. Ann Intern Med 1995;122:521–529.PubMedGoogle Scholar
  2. 2.
    Martinez G, Barbera J, Navasa M, et al.: Hepatopulmonary syndrome associated with cardiorespiratory disease. J. Hepatol. 1999;30:882–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Abrams GA, Jaffe CC, Hoffer PB, et al.: Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology 1995;109:1283–1288.CrossRefPubMedGoogle Scholar
  4. 4.
    Martinez G, Barbera J, Visa J, et al.: Hepatopulmonary Syndrome in candidates for liver transplantation. J. Hepatol. 2001;34:756–758.CrossRefGoogle Scholar
  5. 5.
    Regev A, Yeshurun M, Rodriguez M, et al.: Transient hepatopulmonary syndrome in a patient with acute hepatitis A. J. Viral Hep. 2001;8:83–86.CrossRefGoogle Scholar
  6. 6.
    Teuber G, Teupe C, Dietrich C, et al.: Pulmonary dysfunction in non-cirrhotic patients with chronic viral hepatitis. Eur J Intern Med 2002;13:311–318.CrossRefPubMedGoogle Scholar
  7. 7.
    Fuhrmann V, Madl C, Mueller C, et al.: Hepatopulmonary Syndrome in Patients With Hypoxic Hepatitis. Gastroenterology 2006;131:69–75.CrossRefPubMedGoogle Scholar
  8. 8.
    Dimand RJ, Heyman MB, Bass NM, et al.: Hepatopulmonary syndrome: response to hepatic transplantation. Hepatology 1991;141 (Pt. 2):55A [Abstract].Google Scholar
  9. 9.
    Abrams G, Fallon M: The Hepatopulmonary Syndrome. Clinics in Liver Disease 1997;1:185–200.CrossRefPubMedGoogle Scholar
  10. 10.
    Binay K, Sen S, Biswas PK, et al.: Hepatopulmonary syndrome in inferior vena cava obstruction responding to cavoplasty. Gastroenterology. 2000;118:192–196.CrossRefGoogle Scholar
  11. 11.
    Gupta D, Vijaya DR, Gupta R, et al.: Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction. American Journal of Gastroenterology 2001;96:3395–3399.CrossRefPubMedGoogle Scholar
  12. 12.
    • Fallon M, Krowka M, Brown R, et al.; Pulmonary Vascular Complications of Liver Disease Study Group: Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates. Gastroenterol 2008, Oct;135(4):1168–75. This article describes a recent multicenter prospective study of a large group of liver transplant candidates demonstrating reduced quality of life and survival in patients with HPS. CrossRefGoogle Scholar
  13. 13.
    Schraufnagel D, Kay J: Structural and pathologic changes in the lung vasculature in chronic liver disease. Clinics in Chest Medicine 1996;17:1–15.CrossRefPubMedGoogle Scholar
  14. 14.
    Brussino L, Bucca C, Morello M, et al.: Effect on dyspnoea and hypoxaemia of inhaled NG-nitro-L-arginine methyl ester in hepatopulmonary syndrome. The Lancet 2003;362:43–44.CrossRefGoogle Scholar
  15. 15.
    Schenk P, Madl C, Rezale-Majd S, et al.: Methylene blue improves the hepatopulmonary syndrome. Ann. Int. Med. 2000;133:701–6.PubMedGoogle Scholar
  16. 16.
    Degano B, Mittaine M, Hervé P, et al.: Nitric oxide production by the alveolar compartment of the lungs in cirrhotic patients. Eur Respir J. 2009 Jul;34(1):138–44.CrossRefPubMedGoogle Scholar
  17. 17.
    Fallon MB, Abrams GA, Luo B, et al.: The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome. Gastroenterology 1997;113:606–614.CrossRefPubMedGoogle Scholar
  18. 18.
    Ling Y, Zhang J, Luo B, et al.: The role of endothelin-1 and the endothelin B receptor in the pathogenesis of experimental hepatopulmonary syndrome. Hepatology 2004;39:1593–1602.CrossRefPubMedGoogle Scholar
  19. 19.
    Zhang J, Ling Y, Luo B, et al.: Analysis of pulmonary heme oxygenase-1 and nitric oxide synthase alterations in experimental hepatopulmonary syndrome. Gastroenterology 2003;125:1441–51.CrossRefPubMedGoogle Scholar
  20. 20.
    Carter EP, Hartsfield CL, Miyazono M, et al.: Regulation of heme oxygenase-1 by nitric oxide during hepatopulmonary syndrome. American Journal of Physiology—Lung Cellular & Molecular Physiology. 2002;283:L346–L353.Google Scholar
  21. 21.
    Zhang J, Luo B, Tang L, et al.: Pulmonary Angiogenesis in a Rat Model of Hepatopulmonary Syndrome. Gastroenterology 2009;136:1070–1080.CrossRefPubMedGoogle Scholar
  22. 22.
    Sood G, Fallon MB, Niwas S, et al.: Utility of a dyspnea-fatigue index for screening liver transplant candidates for hepatopulmonary syndrome. Hepatology. 1998;28:2319 [abstract].Google Scholar
  23. 23.
    Robin ED, Laman D, Horn BR, et al.: Platypnea related to orthodeoxia caused by true vascular lung shunts. N Engl J Med 1976;294:941–943.CrossRefPubMedGoogle Scholar
  24. 24.
    Martinez GP, Barbera JA, Visa J, et al.: Hepatopulmonary syndrome in candidates for liver transplantation. Journal of Hepatology. 2001;34(5):651–7.CrossRefPubMedGoogle Scholar
  25. 25.
    McAdams HP, Erasmus J, Crockett R, et al.: The hepatopulmonary syndrome: radiologic findings in 10 patients. Am J Roentgenol 1996;166 (6):1379–85.Google Scholar
  26. 26.
    Lima B, Franca A, Pazin-Filho A, et al.: Frequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome. Mayo Clin Proc 2004;79:42–8.CrossRefPubMedGoogle Scholar
  27. 27.
    Abrams GA, Sanders MK, Fallon MB: Utility of pulse oximetry in the detection of arterial hypoxemia in liver transplant candidates. Liver Transpl.. 2002;8(4):391–6.CrossRefPubMedGoogle Scholar
  28. 28.
    Abrams G, Nanda N, Dubovsky E, et al.: Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome:a new approach. Gastroenterology. 1998;114(305–10).Google Scholar
  29. 29.
    Lee KN, Lee HJ, Shin WW, et al.: Hypoxemia and liver cirrhosis (hepatopulmonary syndrome) in eight patients: comparison of the central and peripheral pulmonary vasculature. Radiology 1999;211:549–553.PubMedGoogle Scholar
  30. 30.
    Swanson K, Wiesner R, Krowka M: Natural history of hepatopulmonary syndrome: Impact of liver transplantation. Hepatology 2005;41:1122–1129.CrossRefPubMedGoogle Scholar
  31. 31.
    Abrams GA, Fallon MB: Treatment of hepatopulmonary syndrome with allium sativum L. (garlic): A pilot trial. J. Clin. Gastro. 1998;27:232–235.CrossRefGoogle Scholar
  32. 32.
    Song JY, Choi JY, Ko JT, et al.: Long-term aspirin therapy for hepatopulmonary syndrome. Pediatrics 1996;97 (6 Pt 1):917–920.PubMedGoogle Scholar
  33. 33.
    Anel RM, Sheagren JN: Novel presentation and approach to management of hepatopulmonary syndrome with use of antimicrobial agents. Clinical Infectious Diseases. 2001;32:E131–136.CrossRefPubMedGoogle Scholar
  34. 34.
    Brussino L, Bucca C, Morello M, et al.: Effect on dyspnoea and hypoxaemia of inhaled NG-nitro-L-arginine methyl ester in hepatopulmonary syndrome. The Lancet 2003;362:43–44.CrossRefGoogle Scholar
  35. 35.
    Tanikella R, Philips G, Faulk D, et al.: Pilot study of pentoxifylline in hepatopulmonary syndrome. Liver Transplantation 2008;14:1199–1203.CrossRefPubMedGoogle Scholar
  36. 36.
    Arguedas M, Abrams GA, Krowka MJ, et al.: Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation. Hepatology 2003;37:192–197.CrossRefPubMedGoogle Scholar
  37. 37.
    • Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB, on behalf of the ERS Task Force Pulmonary-Hepatic Vascular Disorders Scientific Committee ERS Task Force PHD Scientific Committee. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J 2004;24:861–880. Recent comprehensive review of HPS and POPH outlining epidemiology, pathogenesis, diagnosis and current therapies. CrossRefPubMedGoogle Scholar
  38. 38.
    • Colle I, Moreau R, Godinho E, et al.: Portopulmonary Hypertension in Candidates For Liver Transplantation: Diagnosis at Evaluation Comparing Doppler Echocardiography With Cardiac Catheterization and Incidence on The Waiting List. Hepatology 2003;37:401–409. In this study the authors emphasize the importance of Doppler echocardiography as a excellent screening modality for portopulmonary hypertension and the need for right side cardiac catheterization as a confirmatory test. CrossRefPubMedGoogle Scholar
  39. 39.
    Torregrosa M, Genesca J, Gonzalez A, et al.: Role of Doppler echocardiography in the assessment of portopulmonary hypertension in liver transplantation candidates. Transplantation. 2001;71:572–574.CrossRefPubMedGoogle Scholar
  40. 40.
    • Kawut S, Krowka M, Trotter J, et al.: Clinical risk factors for portopulmonary hypertension. Hepatology 2008;48:196–203. This article describes a multicenter case-control study that assessed the different risk factors associated with portopulmonary hypertension. CrossRefPubMedGoogle Scholar
  41. 41.
    Budhiraja R, Hassoun PM: Portopulmonary Hypertension: A Tale of Two Circulations. Chest 2003;123(2):562–576.CrossRefPubMedGoogle Scholar
  42. 42.
    Swanson KL, Krowka MJ: Screen for portopulmonary hypertension, especially in liver transplant candidates. Cleve Clin J Med 2008; 75:121–36.CrossRefPubMedGoogle Scholar
  43. 43.
    Hoeper MM, Krowka MJ, Strassburg CP: Portopulmonary hypertension and hepatopulmonary syndrome. The Lancet 2004;363:1461–1468.CrossRefGoogle Scholar
  44. 44.
    Krowka MJ: Portopulmonary hypertension: Diagnostic advances and caveats. Liver Transpl 2003; 9:1336–7.PubMedGoogle Scholar
  45. 45.
    Murray KF, Carrithers RL, Jr.: AASLD Practice Guidelines: Evaluation of the patient for liver transplantation. Hepatology 2005; 1–26.Google Scholar
  46. 46.
    Swanson K, Wiesner R, Nyberg S, et al.: Survival in Portopulmonary Hypertension: Mayo Clinic Experience Categorized by Treatment Subgroups. American Journal of Transplantation 2008;8:2445–2453.CrossRefPubMedGoogle Scholar
  47. 47.
    Le Pavec J, Souza R, Herve P, et al.: Portopulmonary Hypertension: Survival and Prognostic Factors. Am. J. Respir. Crit. Care Med. 2008;178:637–643.CrossRefPubMedGoogle Scholar
  48. 48.
    Kawut S, Taichman D, Ahya V, et al.: Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl 2005;11:1107–1111.CrossRefPubMedGoogle Scholar
  49. 49.
    Ashfaq M, Chinnakotla S, Rogers L, et al.: The Impact of Treatment of Portopulmonary Hypertension on Survival Following Liver Transplantation. American Journal of Transplantation 2007;7:1258–1264.CrossRefPubMedGoogle Scholar
  50. 50.
    Fix O, Bass N, De Marco T, Merriman R: Long-term follow-up of portopulmonary hypertension: Effect of treatment with epoprostenol. Liver Transplantation 2007;13:875–885.CrossRefPubMedGoogle Scholar
  51. 51.
    Austin MJ, McDougall NI, Wendon JA, et al.: Safety and efficacy of combined use of sildenafil, bosentan, and iloprost before and after liver transplantation in severe portopulmonary hypertension. Liver Transplantation 2008;14:287–291.CrossRefPubMedGoogle Scholar
  52. 52.
    Hoeper MM, Seyfarth HJ, Hoeffken G, et al.: Experience with inhaled iloprost and bosentan in portopulmonary hypertension. Eur Respir J 2007;30:1096–1102.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Rajan Kochar
    • 1
  • Moises I. Nevah Rubin
    • 1
  • Michael B. Fallon
    • 1
    Email author
  1. 1.Division of Gastroenterology, Hepatology, and NutritionThe University of Texas Health Science Center at HoustonHoustonUSA

Personalised recommendations