Skip to main content
SpringerLink
Log in

Portopulmonary Hypertension and Hepatopulmonary Syndrome

  • Chapter
  • First Online:
Orphan Lung Diseases

  • 569 Accesses

Abstract

Portopulmonary hypertension (PoPH) and hepatopulmonary syndrome (HPS) are the two pulmonary vascular disorders that occur in patients with underlying chronic liver disease. Despite being uncommon, these conditions have significant prognostic and therapeutic implications for patients, particularly those considering liver transplantation (LT). Mechanisms of disease pathogenesis in PoPH and HPS are poorly understood but involve vasoactive mediators that bypass liver metabolism, or are generated by liver disease, and drive inappropriate angiogenesis, inflammation, and remodeling of the pulmonary vasculature. Although PoPH and HPS are defined by distinct diagnostic criteria, they can rarely occur simultaneously in the same patient, and the precise relationship between the two is still unclear. Signs and symptoms of PoPH and HPS are nonspecific and are difficult to distinguish from those of underlying chronic liver disease, so it is imperative that clinicians maintain a high index of suspicion for these pulmonary vascular disorders when confronted with a dyspneic patient with hepatic disease (Table 11.1, Fig. 11.1). Both conditions significantly increase the morbidity and mortality of chronic liver disease patients, and aggressive screening for PoPH and HPS is recommended for all liver transplant candidates. Liver transplantation is curative in HPS, and supportive treatment with supplemental oxygen remains the only other approved therapy to show benefit in HPS. Liver transplantation can be effective for PoPH, but outcomes are highly variable, and targeted pulmonary vasodilator therapy is the mainstay of treatment for these patients. Given the high mortality, limited therapeutic options, and unclear molecular pathogenesis of these conditions, additional research into PoPH and HPS is needed in order to improve patient outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Galie N, Humbert M, Vachiery J, Gibbs S, Lang I, Torbicki A, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2015;46:903–75. https://doi.org/10.1016/j.rec.2016.01.002.

    Article  CAS  PubMed  Google Scholar 

  2. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913. https://doi.org/10.1183/13993003.01913-2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Martin P, DiMartini A, Feng S, Brown R Jr, Fallon M. Evaluation for liver transplantation in Adults: 2013 practice guideline by the AASLD and the American society of transplantation. Hepatology. 2014;59(3):1144–65. https://doi.org/10.1002/hep.26972.

    Article  PubMed  Google Scholar 

  4. Krowka MJ, Fallon MB, Kawut SM, Fuhrmann V, Heimbach JK, Ramsay MAE, et al. International liver transplant society practice guidelines: diagnosis and management of hepatopulmonary syndrome and portopulmonary hypertension. Transplantation. 2016;100(7):1440–52. https://doi.org/10.1097/TP.0000000000001229.

    Article  PubMed  Google Scholar 

  5. Porres-Aguilar M, Altamirano JT, Torre-Delgadillo A, Charlton MR, Duarte-Rojo A. Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview. Eur Respir Rev. 2012;21:223–33. https://doi.org/10.1183/09059180.00007211.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Saleemi S. Portopulmonary hypertension. Ann Thorac Med. 2010;5(1):5–9. https://doi.org/10.4103/1817-1737.58953.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bartolome SD. Portopulmonary hypertension: diagnosis, clinical features, and medical therapy. Clin Liver Dis. 2014;4(2):42–5. https://doi.org/10.1002/cld.401.

    Article  Google Scholar 

  8. Schouten JNL, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis. 2015;10:67. https://doi.org/10.1186/s13023-015-0288-8.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Sithamparanathan S, Nair A, Thirugnanasothy L, Coghlan JG, Condliffe R, Dimopoulos K, et al. Survival in portopulmonary hypertension: outcomes of the united kingdom national pulmonary arterial hypertension registry. J Heart Lung Transplant. 2017;36(7):770–9. https://doi.org/10.1016/j.healun.2016.12.014.

    Article  PubMed  Google Scholar 

  10. Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023–30. https://doi.org/10.1164/rccm.200510-1668OC.

    Article  PubMed  Google Scholar 

  11. Cosarderelioglu C, Cosar AM, Gurakar M, Pustavoitau A, Russell SD, Dagher NN, et al. Portopulmonary hypertension and liver transplant: recent review of the literature. Exp Clin Transplant. 2016;14(2):113–20.

    PubMed  Google Scholar 

  12. Kawut S, Krowka MJ, Trotter JF, Roberts KE, Benza RL, Badesch DB, et al. Clinical risk factors for portopulmonary hypertension. Hepatology. 2008;48(1):196–203. https://doi.org/10.1002/hep.22275.

    Article  PubMed  Google Scholar 

  13. DuBrock HM, Goldberg DS, Sussman NL, Bartolome SD, Kadry Z, Salgia RJ, et al. Predictors of waitlist mortality in portopulmonary hypertension. Transplantation. 2017;101(7):1609–15. https://doi.org/10.1097/TP.0000000000001666.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Reynaert H, Thompson MG, Thomas T, Geerts A. Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. Gut. 2002;50(4):571–81. https://doi.org/10.1136/gut.50.4.571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Gandi CR. Hepatic stellate cell activation and pro-fibrogenic signals. J Hepatol. 2017;67(5):1104–5. https://doi.org/10.1016/j.jhep.2017.06.001.

    Article  Google Scholar 

  16. Benjaminov FS, Prentice M, Sniderman KW, Siu S, Liu P, Wong F. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut. 2003;52(9):1355–62. https://doi.org/10.1136/gut.52.9.1355.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pellicelli AM, Barbaro G, Puoti C, Guarascio P, Lusi EA, Bellis L, et al. Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation. Angiology. 2010;61(8):802–6. https://doi.org/10.1177/0003319710369101.

    Article  CAS  PubMed  Google Scholar 

  18. DuBrock HM, Rodriguez-Lopez JM, LeVarge BL, Curry MP, VanderLaan PA, Zsengeller ZK, et al. Macrophage migration inhibitory factor as a novel biomarker of portopulmonary hypertension. Pulm Circ. 2016;6(4):498–507. https://doi.org/10.1086/688489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nikolic I, Yung LM, Yang P, Malhotra R, Paskin-Flerlage SD, Dinter T, et al. Bone morphogenic protein 9 is a mechanistic biomarker of portopulmonary hypertension. Am J Respir Crit Care Med. 2019;199(7):891–902. https://doi.org/10.1164/rccm.201807-1236OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rochon ER, Krowka MJ, Bartolome S, Heresi GA, Bull T, Roberts K, et al. BMP 9/10 in pulmonary vascular complications of liver disease. Am J Respir Crit Care Med. 2020;201(12):1575–8. https://doi.org/10.1164/rccm.201912-2514LE.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Breitkopf-Heinlein K, Meyer C, Konig C, Gaitantzi H, Addante A, Thomas M, et al. BMP-9 interferes with liver regeneration and promotes liver fibrosis. Gut. 2017;66(5):939–54. https://doi.org/10.1136/gutjnl-2016-313314.

    Article  CAS  PubMed  Google Scholar 

  22. Hodgson J, Swietlik EM, Salmon RM, Hadinnapola C, Nikolic I, Wharton J, et al. Characterization of GDF2 mutations and levels of BMP9 and BMP10 in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2020;201(5):575–85. https://doi.org/10.1164/rccm.201906-1141OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Roberts KE, Fallon MB, Krowka MJ, Brown RS, Trotter JF, Peter I, et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179(9):835–42. https://doi.org/10.1164/rccm.200809-1472OC.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ramachandran P, Dobie R, Wilson-Kanamori JR, Dora EF, Henderson BEP, Luu NT, et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature. 2019;575:512–8. https://doi.org/10.1038/s41586-019-1631-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502–10. https://doi.org/10.1002/hep.21431.

    Article  PubMed  Google Scholar 

  26. Colle IO, Moreau R, Godinho E, Belghiti J, Ettori F, Cohen-Solal A, et al. Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. Hepatology. 2003;37(2):401–9. https://doi.org/10.1053/jhep.2003.50060.

    Article  PubMed  Google Scholar 

  27. Bernal V, Pascual I, Esquivias P, Garcia-Gil A, Mateo JM, Lascambra I, et al. N-terminal brain natriuretic peptide as a diagnostic test in cirrhotic patients with pulmonary arterial hypertension. Transplant Proc. 2009;41(3):987–8. https://doi.org/10.1016/j.transproceed.2009.02.025.

    Article  CAS  PubMed  Google Scholar 

  28. Kim WR, Krowka MJ, Plevak DJ, Lee J, Rettke SR, Frantz RP, et al. Accuracy of doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates. Liver Transpl. 2000;6(4):453–8. https://doi.org/10.1053/jlts.2000.7573.

    Article  PubMed  Google Scholar 

  29. Habash F, Gurram P, Almomani A, Duarte A, Hakeem A, Vallurupalli S, et al. Correlation between echocardiographic pulmonary artery pressure estimates and right heart catheterization measurement in liver transplant candidates. J Cardiovasc Imaging. 2018;26(2):75–84. https://doi.org/10.4250/jcvi.2018.26.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Cotton CL, Gandhi S, Vaitkus PT, Massad MG, Benedetti E, Mrtek RG, et al. Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates. Liver Transpl. 2002;8(11):1051–4. https://doi.org/10.1053/jlts.2002.35554.

    Article  PubMed  Google Scholar 

  31. Kovacs G, Berghold A, Scheidl S, Olschewski H. Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review. Eur Respir J. 2009;34:888–94.

    Article  CAS  PubMed  Google Scholar 

  32. Blendis L, Wong F. The hyperdynamic circulation in cirrhosis: an overview. Pharmacol Ther. 2001;89(3):221–31. https://doi.org/10.1183/09031936.00145608.

    Article  CAS  PubMed  Google Scholar 

  33. Pozzi M, Ratti L, Redaelli E, Guidi C, Mancia G. Cardiovascular abnormalities in special conditions of advanced cirrhosis: the circulatory adaptive changes to specific therapeutic procedures for the management of refractory ascites. Gastroenterol Hepatol. 2006;29(4):264–72. https://doi.org/10.1157/13086820.

    Article  Google Scholar 

  34. Goldberg DS, Batra S, Sahay S, Kawut SM, Fallon MB. MELD exceptions for portopulmonary hypertension: current policy and future implementation. Am J Transplant. 2014;14(9):2081–7. https://doi.org/10.1111/ajt.12783.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Le Pavec J, Souza R, Herve P, Lebrec D, Savale L, Tcherakian C, et al. Portopulmonary hypertension: survival and prognostic factors. Am J Respir Crit Care Med. 2008;178(6):637–43. https://doi.org/10.1164/rccm.200804-613OC.

    Article  PubMed  Google Scholar 

  36. Swanson KL, Wiesner RH, Nyberg SL, Rosen CB, Krowka MJ. Survival in portopulmonary hypertension: Mayo clinic experience categorized by treatment subgroups. Am J Transplant. 2008;8(11):2445–53. https://doi.org/10.1111/j.1600-6143.2008.02384.x.

    Article  CAS  PubMed  Google Scholar 

  37. Krowka MJ, Mandell MS, Ramsay MA, Kawut SM, Fallon MB, Manzarbeitia C, et al. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database. Liver Transpl. 2004;10(2):174–82. https://doi.org/10.1002/lt.20016.

    Article  PubMed  Google Scholar 

  38. Li J, Zhuang Q, Zhang X, Zheng Y, Qiao Z, Zhang J, et al. Prevalence and prognosis of portopulmonary hypertension in 223 liver transplant recipients. Can Respir J. 2018;2018:9629570. https://doi.org/10.1155/2018/9629570.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Krowka MJ, Plevak DJ, Findlay JY, Rosen CB, Wiesner RH, Krom RA. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000;6(4):443–50. https://doi.org/10.1053/jlts.2000.6356.

    Article  CAS  PubMed  Google Scholar 

  40. Ashfaq M, Chinnakolta S, Rogers L, Ausloos K, Saadeh S, Klintmalm GB, et al. The impact of treatment of portopulmonary hypertension on survival following liver transplantation. Am J Transplant. 2007;7(5):1258–64. https://doi.org/10.1111/j.1600-6143.2006.01701.x.

    Article  CAS  PubMed  Google Scholar 

  41. Bandara M, Gordon FD, Sarwar A, Knauflt ME, Pomfret EA, Freeman RB, et al. Successful outcomes following living donor liver transplantation for portopulmonary hypertension. Liver Transpl. 2010;16(8):983–9. https://doi.org/10.1002/lt.22107.

    Article  PubMed  Google Scholar 

  42. DuBrock HM, Salgia RJ, Sussman NL, Bartolome SD, Kadry Z, Mulligan DC, et al. Portopulmonary hypertension: a survey of practice patterns and provider attitudes. Transpl Dir. 2019;5(6):e456. https://doi.org/10.1097/TXD.0000000000000900.

    Article  Google Scholar 

  43. Huang B, Shi Y, Liu J, Schroder PM, Deng S, Chen M, et al. The early outcomes of candidates with portopulmonary hypertension after liver transplantation. BMC Gastroenterol. 2018;18:79. https://doi.org/10.1186/s12876-018-0797-8.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Starkel P, Vera A, Gunson B, Mutimer D. Outcome of liver transplantation for patients with pulmonary hypertension. Liver Trasnpl. 2002;8(4):382–8. https://doi.org/10.1053/jlts.2002.31343.

    Article  Google Scholar 

  45. Bozbas SS, Eyuboglu FO, Arslan NG, Ergur FO, Karakayali H, Haberal M. The prevalence and the impact of portopulmonary hypertension on postoperative course in patients undergoing liver transplantation. Transplant Proc. 2009;41(7):2860–3. https://doi.org/10.1016/j.transproceed.2009.06.178.

    Article  CAS  PubMed  Google Scholar 

  46. Khaderi S, Khan R, Safdar Z, Stribling R, Vierling JM, Goss JA, et al. Long-term follow-up of portopulmonary hypertension patients after liver transplantation. Liver Transpl. 2014;20(6):724–7. https://doi.org/10.1002/lt.23870.

    Article  PubMed  Google Scholar 

  47. Savale L, Sattler C, Coilly A, Conti F, Renard S, Francoz C, et al. Long-term outcome in liver transplantation candidates with portopulmonary hypertension. Hepatology. 2017;65(5):1683–92. https://doi.org/10.1002/hep.28990.

    Article  CAS  PubMed  Google Scholar 

  48. Sitbon O, Bosch J, Cottreel E, Csonka D, Groote P, Hoeper MM, et al. Macitentan for the treatment of portopulmonary hypertension (PORTICO): a multicenter, randomized, double-blind, placebo-controlled, phase 4 trial. Lancet Respir Med. 2019;7(7):594–604. https://doi.org/10.1016/S2213-2600(19)30091-8.

    Article  CAS  PubMed  Google Scholar 

  49. Preston IR, Burger CD, Bartolome S, Safdar Z, Krowka M, Sood N, et al. Ambrisentan in portopulmonary hypertension: a multicenter, open-label trial. J Heart Lung Transplant. 2020;39(5):464–72. https://doi.org/10.1016/j.healun.2019.12.008.

    Article  PubMed  Google Scholar 

  50. Cartin-Ceba R, Swanson K, Iyer V, Wiesner RH, Krowka MJ. Safety and efficacy of ambrisentan for the treatment of portopulmonary hypertension. Chest. 2011;139(1):109–14. https://doi.org/10.1378/chest.10-057.

    Article  CAS  PubMed  Google Scholar 

  51. Cartin-Ceba R, Halank M, Ghofrani H, Humbert M, Mattson J, Fritsch A, et al. Riociguat treatment for portopulmonary hypertension: a subgroup analysis from the PATENT-1/-2 studies. Pulm Circ. 2018;8(2):2045894018769305. https://doi.org/10.1177/2045894018769305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Riechenberger F, Voswinckel R, Steveling E, Enke B, Kreckel A, Olschewski H, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006;28(3):563–7. https://doi.org/10.1183/09031936.06.00030206.

    Article  CAS  Google Scholar 

  53. Fisher JH, Johnson SR, Chau C, Kron AT, Granton JT. Effectiveness of phosophodiesterase-5 inhibitor therapy for portopulmonary hypertension. Can Respir J. 2015;22(1):42–6. https://doi.org/10.1155/2015/810376.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Faisal M, Siddiqui F, Alkaddour A, Bajwa AA, Shujaat A. Effect of PAH specific therapy on pulmonary hemodynamics and six-minute walk distance in portopulmonary hypertension: a systematic review and meta-analysis. Pulm Med. 2014;2014:528783. https://doi.org/10.1155/2014/528783.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Yamashita Y, Tsujino I, Sato T, Yamada A, Watanabe T, Ohira H, et al. Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension. World J Hepatol. 2014;6(11):825–9. https://doi.org/10.4254/wjh.v6.i11.825.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Hemnes AR, Robbins IM. Sildenafil monotherapy in portopulmonary hypertension can facilitate liver transplantation. Liver Transpl. 2009;15(1):15–9. https://doi.org/10.1002/lt.21479.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Gough MS, White RJ. Sildenafil therapy is associated with improved hemodynamics in liver transplantation candidates with pulmonary arterial hypertension. Liver Transpl. 2009;15(1):30–6. https://doi.org/10.1002/lt.21533.

    Article  PubMed  Google Scholar 

  58. Kuo PC, Johnson LB, Plotkin JS, Howell CD, Bartlett ST, Rubin LJ. Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension. Transplantation. 1997;63(4):604–6. https://doi.org/10.1097/00007890-199702270-00020.

    Article  CAS  PubMed  Google Scholar 

  59. Krowka MJ, Frantz RP, McGoon MD, Severson C, Plevak DJ, Wiesner RH. Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): a study of 15 patients with moderate to severe portopulmonary hypertension. Hepatology. 1999;30(3):641–8. https://doi.org/10.1002/hep.510300307.

    Article  CAS  PubMed  Google Scholar 

  60. Fix OK, Bass NM, De Marco T, Merriman RB. Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl. 2007;13(6):875–85. https://doi.org/10.1002/lt.21174.

    Article  PubMed  Google Scholar 

  61. Sitbon O, Vonk Noordegraaf A. Epoprostenol and pulmonary arterial hypertension: 20 years of clinical experience. Eur Respir Rev. 2017;26:160055. https://doi.org/10.1183/16000617.0055-2016.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Barst RJ, Rubin LJ, Wong WA, McGoon MD, Rich S, Badesch DB, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996;334(5):296–301. https://doi.org/10.1056/NEJM199602013340504.

    Article  CAS  PubMed  Google Scholar 

  63. AbuHalimeh B, Krowka MJ, Tonelli AR. Treatment barriers in portopulmonary hypertension. Hepatology. 2018;69(1):431–43. https://doi.org/10.1002/hep.30197.

    Article  PubMed  Google Scholar 

  64. Provencher S, Herve P, Jais X, Lebrec D, Humbert M, Simonneau G, et al. Deleterious effects of beta-blockers on exercise capacity and hemodynamics in patients with portopulmonary hypertension. Gastroenterology. 2006;130(1):120–6. https://doi.org/10.1053/j.gastro.2005.10.013.

    Article  CAS  PubMed  Google Scholar 

  65. Aday AW, Mayo MJ, Elliott A, Rockey DC. The beneficial effect of beta-blockers in patients with cirrhosis, portal hypertension, and ascites. Am J Med Sci. 2016;351(2):169–76. https://doi.org/10.1016/j.amjms.2015.11.018.

    Article  PubMed  Google Scholar 

  66. Bandyopadhyay D, Bajaj NS, Zein J, Minai OA, Dweik RA. Outcomes of b-blocker use in pulmonary arterial hypertension: a propensity-matched analysis. Eur Respir J. 2015;46(3):750–60. https://doi.org/10.1183/09031936.00215514.

    Article  CAS  PubMed  Google Scholar 

  67. Lv Y, Yang Z, Liu L, Li K, He C, Wang Z, et al. Early TIPS with covered stents versus standard treatment for acute variceal bleeding in patients with advanced cirrhosis: a randomized controlled trial. Lancet. 2019;4(8):587–98. https://doi.org/10.1016/S2468-1253(19)30090-1.

    Article  Google Scholar 

  68. Merli M, Salerno F, Riggio O, de Franchis R, Fiaccadori F, Meddi P, et al. Transjugular intrahepatic portosystemic shunt versus endoscopic sclerotherapy for the prevention of variceal bleeding in cirrhosis: a randomized multicenter trial. Hepatology. 1998;27(1):48–53. https://doi.org/10.1002/hep.510270109.

    Article  CAS  PubMed  Google Scholar 

  69. Van der Linden P, Le Moine O, Ghysels M, Ortinez M, Deviere J. Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function. Hepatology. 1996;23(5):982–7. https://doi.org/10.1053/jhep.1996.v23.pm0008621179.

    Article  PubMed  Google Scholar 

  70. Chung S, Lee K, Chang S, Kim D. Aggravation of hepatopulmonary syndrome after sildenafil treatment in a patient with coexisting portopulmonary hypertension. Korean Circ J. 2015;45(1):77–80. https://doi.org/10.4070/kcj.2015.45.1.77.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Zopey R, Susanto I, Barjaktarevic I, Wang T. Transition from hepatopulmonary syndrome to portopulmonary hypertension: a case series of 3 patients. Case Rep Pulmonol. 2013;2013:561870. https://doi.org/10.1155/2013/561870.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Fallon MB, Krowka MJ, Brown RS, Trotter JF, Zacks S, Roberts KE, et al. Impact of hepatopulmonary syndrome on quality of life and survival in liver transplant candidates. Gastroentrology. 2008;135(4):1168–75. https://doi.org/10.1053/j.gastro.2008.06.038.

    Article  Google Scholar 

  73. Soulaidopoulos S, Cholongitas E, Giannakoulas G, Vlachou M, Goulis I. Review article: update on current and emerging data on hepatopulmonary syndrome. World J Gastroenterol. 2018;24(12):1285–98. https://doi.org/10.3748/wjg.v24.i12.1285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cosarderelioglu C, Cosar AM, Gurakar M, Dagher NN, Gurakar A. Hepatopulmonary syndrome and liver transplantation: a recent review of the literature. J Clin Transl Hepatol. 2016;4(1):47–53. https://doi.org/10.14218/JCTH.2015.00044.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Nunes H, Lebrec D, Mazmanian M, Capron F, Heller J, Tazi KA, et al. Role of nitric oxide in hepatopulmonary syndrome in cirrhotic rats. Am J Respir Crit Care Med. 2001;164(5):879–85. https://doi.org/10.1164/ajrccm.164.5.2009008.

    Article  CAS  PubMed  Google Scholar 

  76. Rabiller A, Nunes H, Lebrec D, Tazi KA, Wartski M, Dulmet E, et al. Prevention of gram-negative translocation reduces severity of hepatopulmonary syndrome. Am J Respir Crit Care Med. 2002;166(4):514–7. https://doi.org/10.1164/rccm.200201-027OC.

    Article  PubMed  Google Scholar 

  77. Thenappan T, Goel A, Marsboom G, Fang Y, Toth PT, Zhang HJ, et al. A central role for CD68+ macrophages in hepatopulmonary syndrome. Reversal by macrophage depletion. Am J Respir Crit Care Med. 2011;183(8):1080–91. https://doi.org/10.1164/rccm.201008-1303OC.

    Article  PubMed  Google Scholar 

  78. Cremona G, Higenbottam TW, Mayoral V, Alexander G, Demoncheaux E, Borland C, et al. Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome. Eur Respir J. 1995;8(11):1883–5. https://doi.org/10.1183/09031936.95.08111883.

    Article  CAS  PubMed  Google Scholar 

  79. Sztrymf B, Libert J, Mougeot C, Lebrec D, Mazmanian M, Humbert M, et al. Cirrhotic rats with bacterial translocation have higher incidence and severity of hepatopulmonary syndrome. J Gastroenterol Hepatol. 2005;20(10):1538–44. https://doi.org/10.1111/j.1440-1746.2005.03914.x.

    Article  CAS  PubMed  Google Scholar 

  80. Ling Y, Zhang J, Luo B, Song D, Liu L, Tang L, et al. The role of endothelin-1 and endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat. Hepatology. 2004;39(6):1593–602. https://doi.org/10.1002/hep.20244.

    Article  CAS  PubMed  Google Scholar 

  81. Zhang J, Ling Y, Tang L, et al. Attenuation of experimental hepatopulmonary syndrome in endothelin B receptor-deficient rats. Am J Physiol Gastrointest Liver Physiol. 2009;296(4):G704–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Luo B, Liu L, Tang L, Luo B, Pollock DM, Fallon MB. Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. J Hepatol. 2003;38(5):556–63. https://doi.org/10.1152/ajpgi.90627.2008.

    Article  CAS  PubMed  Google Scholar 

  83. Roberts KE, Kawut SM, Krowka MJ, Brown RS, Trotter JF, Shah V, et al. Genetic risk factors for hepatopulmonary syndrome in patients with advanced liver disease. Gastroenterology. 2010;139(1):130–9.e24. https://doi.org/10.1053/j.gastro.2010.03.044. Epub 24 Mar 2010.

    Article  CAS  PubMed  Google Scholar 

  84. Alizadeh AHM, Fatemi SR, Mirzaee V, Khoshbaten M, Talebipour B, Sharifian A, et al. Clinical features of hepatopulmonary syndrome in cirrhotic patients. World J Gastroenterol. 2006;12(12):1954–6. https://doi.org/10.3748/wjg.v12.i12.1954.

    Article  PubMed Central  Google Scholar 

  85. Forde KA, Fallow MB, Krowka MJ, Sprys M, Goldberg DS, Krok KL, et al. Pulse oximetry is insensitive for detection of hepatopulmonary syndrome in patients evaluated for liver transplantation. Hepatology. 2019;69(1):270–81. https://doi.org/10.1002/hep.30139.

    Article  CAS  PubMed  Google Scholar 

  86. Arguedas MR, Singh H, Faulk DK, Fallon MB. Utility of pulse oximetry screening for hepatopulmonary syndrome. Clin Gastroenterol Hepatol. 2007;5(6):749–54. https://doi.org/10.1016/j.cgh.2006.12.003.

    Article  PubMed  Google Scholar 

  87. Gomez FP, Martinez-Palli G, Barbera JA, Roca J, Navas M, Rodriguez-Roisin R. Gas exchange mechanism of orthodeoxia in hepatopulmonary syndrome. Hepatology. 2004;40(3):660–6. https://doi.org/10.1002/hep.20358.

    Article  PubMed  Google Scholar 

  88. Diebert P, Allgaier H, Loesch S, Muller C, Olschewski M, Hamm H, et al. Hepatopulmonary syndrome in patients with chronic liver disease: role of pulse oximetry. BMC Gastroenterol. 2006;6:15. https://doi.org/10.1186/1471-230X-6-15.

    Article  Google Scholar 

  89. Schenk P, Fuhrmann V, Madl C, Funk G, Lehr S, Kandel O, et al. Hepatopulmonary syndrome: prevalence and predictive value of various cut offs for arterial oxygenation and their clinical consequences. Gut. 2002;51(6):853–9. https://doi.org/10.1136/gut.51.6.853.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Rodriguez-Roisin R, Krowka MJ. Hepatopulmonary syndrome – a liver-induced lung vascular disorder. N Engl J Med. 2008;358(22):2378–87. https://doi.org/10.1056/NEJMra0707185.

    Article  CAS  PubMed  Google Scholar 

  91. Abrams GA, Jaffe CC, Hoffer PB, Binder JH, Fallon MB. Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome. Gastroenterology. 1995;109(4):1283–8. https://doi.org/10.1016/0016-5085(95)90589-8.

    Article  CAS  PubMed  Google Scholar 

  92. van Gent MWF, Post MC, Snijder RJ, Swaans MJ, Plokker HWM, Westermann CJJ, et al. Grading of pulmonary right-to-left shunt with transthoracic contrast echocardiography: does it predict the indication for embolotherapy? Chest. 2009;135(5):1288–92. https://doi.org/10.1378/chest.08-1266.

    Article  PubMed  Google Scholar 

  93. Surasi DS, Manapragada P, Bhambhvani P. Lung perfusion imaging in hepatopulmonary syndrome using 99mTc macroaggregated albumin. J Nucl Cardiol. 2015;22:586–8. https://doi.org/10.1007/s12350-014-9990-5.

    Article  PubMed  Google Scholar 

  94. Abrams GA, Nanda NC, Dubovsky EV, Krowka MJ, Fallon MB. Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach. Gastroenterology. 1998;114(2):P305–10. https://doi.org/10.1016/s0016-5085(98)70481-0.

    Article  Google Scholar 

  95. Arguedas MR, Abrams GA, Krowka MJ, Fallon MB. Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation. Hepatology. 2003;37(1):192–7. https://doi.org/10.1053/jhep.2003.50023.

    Article  PubMed  Google Scholar 

  96. Stoller JK, Lange PA, Westveer MK, Carey WD, Vogt D, Henderson JM. Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic Experience. West J Med. 1995;163(2):133–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Schiffer E, Manjo P, Mentha G, Giostra E, Burri H, Klopfenstein CE, et al. Hepatopulmonary syndrome increases the postoperative mortality rate following liver transplantation: a prospective study in 90 patients. Am J Transplant. 2006;6(6):1430–7. https://doi.org/10.1111/j.1600-6143.2006.01334.x.

    Article  CAS  PubMed  Google Scholar 

  98. Pacasio JM, Grilo I, Lopez-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, et al. Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation. Am J Transplant. 2014;14(6):1391–9. https://doi.org/10.1111/ajt.12713.

    Article  CAS  Google Scholar 

  99. Raevens S, Rogiers X, Geerts A, Verhelst X, Samuel U, van Rosmalen M, et al. Outcome of liver transplantation for hepatopulmonary syndrome: a Eurotransplant experience. Eur Respir J. 2019;53(2):1801096. https://doi.org/10.1183/13993003.01096-2018.

    Article  PubMed  Google Scholar 

  100. Swanson KL, Wiesner RH, Krowka MJ. Natural history of hepatopulmonary syndrome: impact of liver transplantation. Hepatology. 2005;41(5):1122–9. https://doi.org/10.1002/hep.20658.

    Article  PubMed  Google Scholar 

  101. Goldberg DS, Krok K, Batra S, Trotter JF, Kawut SM, Fallon MB. Impact of the hepatopulmonary syndrome MELD exception policy on outcomes of patients after liver transplantation: an analysis of the UNOS database. Gastroenterology. 2014;146(5):1256–1265.e1. https://doi.org/10.1053/j.gastro.2014.01.005.

    Article  PubMed  Google Scholar 

  102. Krowka MJ, Dickson ER, Cortese DA. Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue. Chest. 1993;104(2):515–21. https://doi.org/10.1378/chest.104.2.515.

    Article  CAS  PubMed  Google Scholar 

  103. Soderman C, Juhlin-Dannfelt A, Lagerstrand L, Eriksson LS. Ventilation-perfusion relationships and central haemodynamics in patients with cirrhosis. Effects of a somatostatin analogue. J Hepatol. 1994;21(1):52–7. https://doi.org/10.1016/s0168-8278(94)80136-3.

    Article  CAS  PubMed  Google Scholar 

  104. Gomez FP, Barbera JA, Roca J, Burgos F, Gistau C, Rodriguez-Roisin R. Effects of nebulized N(G)-nitro-L-arginine methyl ester in patients with hepatopulmonary syndrome. Hepatology. 2006;43(5):1084–91. https://doi.org/10.1002/hep.21141.

    Article  CAS  PubMed  Google Scholar 

  105. Abrams GA, Fallon MB. Treatment of hepatopulmonary syndrome with allium sativum L. (garlic): a pilot study. J Clin Gastroenterol. 1998;27(3):232–5.

    Article  CAS  PubMed  Google Scholar 

  106. Kawut SM, Ellenberg SS, Krowka MJ, et al. Sorafenib in hepatopulmonary syndrome: a randomized, double-blind, placebo-controlled trial. Liver Transpl. 2019;25(8):1155–64. https://doi.org/10.1097/00004836-199810000-00010.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Zhou H, Liu F, Yue Z, Wang L, Fan Z, He F. Clinical efficacy of transjugular intrahepatic portosystemic shunt in the treatment of hepatopulmonary syndrome. Medicine (Baltimore). 2017;96(49):e9080. https://doi.org/10.1097/MD.0000000000009080.

    Article  Google Scholar 

  108. Grady K, Gowda S, Kingah P, Soubani AO. Coil embolization of pulmonary arteries as a palliative treatment of diffuse type I hepatopulmonary syndrome. Respir Care. 2015;60(2):e20–5. https://doi.org/10.4187/respcare.03198.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Arun Jose, Francis X. McCormack & Jean M. Elwing

  2. Pulmonary Hypertension, Cincinnati VA Medical Center, Cincinnati, OH, USA

    Arun Jose & Chandrashekar J. Gandhi

  3. Division of Transplantation, Department of Surgery, University of Cincinnati, Cincinnati, OH, USA

    Shimul A. Shah

  4. Divisions of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Chandrashekar J. Gandhi

Authors
  1. Arun Jose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shimul A. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chandrashekar J. Gandhi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francis X. McCormack
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jean M. Elwing
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arun Jose .

Editor information

Editors and Affiliations

  1. Department of Respiratory Medicine, National Coordinating Reference Centre for Rare Pulmonary Diseases (OrphaLung), Louis Pradel Hospital, University of Lyon, Lyon, France

    Vincent Cottin

  2. Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, Italy

    Luca Richeldi

  3. National Jewish Health, Denver, CO, USA

    Kevin Brown

  4. Division of Pulmonary, Critical Care, and Sleep Medicine Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Francis X. McCormack

Rights and permissions

Reprints and permissions

Copyright information

© 2023 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jose, A., Shah, S.A., Gandhi, C.J., McCormack, F.X., Elwing, J.M. (2023). Portopulmonary Hypertension and Hepatopulmonary Syndrome. In: Cottin, V., Richeldi, L., Brown, K., McCormack, F.X. (eds) Orphan Lung Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-12950-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-12950-6_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-12949-0

  • Online ISBN: 978-3-031-12950-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation