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Review Article

Portopulmonary hypertension

, &
Pages 795-806 | Received 27 Jan 2016, Accepted 20 Feb 2016, Published online: 22 Mar 2016

References

  • Hoeper MM, Krowka MJ, Strassburg CP. Portopulmonary hypertension and hepatopulmonary syndrome. Lancet. 2004;363:1461–1468.
  • Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology. 2014;59:1627–1637.
  • Rodriguez-Roisin R, Krowka MJ, Herve P, et al. Pulmonary-hepatic vascular disorders (PHD). Eur Respir J. 2004;24:861–880.
  • Porres-Aguilar M, Mukherjee D. Portopulmonary hypertension: an update. Respirology. 2015;20:235–242.
  • Cartin-Ceba R, Krowka MJ. Portopulmonary hypertension. Clin Liver Dis. 2014;18:421–438.
  • Safdar Z, Bartolome S, Sussman N. Portopulmonary hypertension: an update. Liver Transpl. 2012;18:881–891.
  • Rodriquez-Roisin R, Krowka MJ, Herve P, et al. Highlights of the ERS Task Force on pulmonary-hepatic vascular disorders (PHD). J Hepatol. 2005;42:924–927.
  • Mantz FJ, Craige E. Portal axis thrombosis with spontaneous portacaval shunt and resultant cor pulmonale. AMA Arch Pathol. 1951;52:91–97.
  • Lebrec D, Capron JP, Dhumeaux D, et al. Pulmonary hypertension complicating portal hypertension. Am Rev Respir Dis. 1979;120:849–856.
  • Herve P, Lebrec D, Brenot F, et al. Pulmonary vascular disorders in portal hypertension. Eur Respir J. 1998;11:1153–1166.
  • Herve P, Le Pavec J, Sztrymf B, et al. Pulmonary vascular abnormalities in cirrhosis. Best Pract Res Clin Gastroenterol. 2007;21:141–159.
  • Porres-Aguilar M, Gallegos-Orozco JF, Garcia H, et al. Pulmonary vascular complications in portal hypertension and liver disease: a concise review. Rev Gastroenterol Mex. 2013;78:35–44.
  • Fritz JS, Fallon MB, Kawut SM. Pulmonary vascular complications of liver disease. Am J Respir Crit Care Med. 2013;187:133–143.
  • Horvatits T, Fuhrmann V. Therapeutic options in pulmonary hepatic vascular diseases. Expert Rev Clin Pharmacol. 2014;7:31–42.
  • Al-Harbi A, Abdullah K, Al-Abdulkareem A, et al. Prevalence of portopulmonary hypertension among liver transplant candidates in a region highly endemic for viral hepatitis. Ann Transplant. 2014;19:1–5.
  • Chen HS, Xing SR, Xu WG, et al. Portopulmonary hypertension in cirrhotic patients: prevalence, clinical features and risk factors. Exp Ther Med. 2013;5:819–824.
  • Krowka MJ, Swanson KL, Frantz RP, et al. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44:1502–1510.
  • Raevens S, Colle I, Reyntjens K, et al. Echocardiography for the detection of portopulmonary hypertension in liver transplant candidates: an analysis of cutoff values. Liver Transpl. 2013;19:602–610.
  • Cotton CL, Gandhi S, Vaitkus PT, et al. Role of echocardiography in detecting portopulmonary hypertension in liver transplant candidates. Liver Transpl. 2002;8:1051–1054.
  • Colle I. Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study. Hepatology. 2003;37:401–409.
  • Perkins JD. Screening for portopulmonary hypertension. Liver Transpl. 2007;13:463–464.
  • Farzaneh-Far R, McKeown BH, Dang D, et al. Accuracy of Doppler-estimated pulmonary vascular resistance in patients before liver transplantation. Am J Cardiol. 2008;101:259–262.
  • Krowka MJ, Miller DP, Barst RJ, et al. Portopulmonary hypertension: a report from the US-based REVEAL Registry. Chest. 2012;141:906–915.
  • Yang YY, Lin HC, Lee WC, et al. Portopulmonary hypertension: distinctive hemodynamic and clinical manifestations. J Gastroenterol. 2001;36:181–186.
  • Ghayumi SM, Mehrabi S, Zamirian M, et al. Pulmonary complications in cirrhotic candidates for liver transplantation. Hepat Mon. 2010;10:105–109.
  • Gayathri AP, Jaya DR, Anjali AD, et al. Portopulmonary hypertension in a case of non-cirrhotic portal fibrosis. Indian J Pathol Microbiol. 2007;50:828–830.
  • Kobayashi D, Edwards HD, Singh J, et al. Portopulmonary hypertension secondary to congenital extrahepatic portosystemic shunt with heterotaxy and polysplenia: a cause of sudden death in an infant. Pediatr Pulmonol. 2011;46:1041–1044.
  • Saunders JB, Constable TJ, Heath D, et al. Pulmonary hypertension complicating portal vein thrombosis. Thorax. 1979;34:281–283.
  • Kawut SM, Krowka MJ, Trotter JF, et al. Clinical risk factors for portopulmonary hypertension. Hepatology. 2008;48:196–203.
  • Budhiraja R, Hassoun PM. Portopulmonary hypertension: a tale of two circulations. Chest. 2003;123:562–576.
  • Krowka MJ, McGoon MD. Portopulmonary hypertension: the next step. Chest. 1997;112:869–870.
  • Porres-Aguilar M, Zuckerman MJ, Figueroa-Casas JB, et al. Portopulmonary hypertension: state of the art. Ann Hepatol. 2008;7:321–330.
  • Fallon MB. Portopulmonary hypertension: mew clinical insights and more questions on pathogenesis. Hepatology. 2003;37:253–255.
  • Krowka MJ, Edwards WD. A spectrum of pulmonary vascular pathology in portopulmonary hypertension. Liver Transpl. 2000;6:241–242.
  • Feltracco P, Serra E, Brezzi ML, et al. Hemodynamic profile of portopulmonary hypertension. Transplant Proc. 2009;41:1235–1239.
  • Yeshua H, Blendis LM, Oren R. Pulmonary manifestations of liver diseases. Sem Cardiothoracic Vasc Anesth. 2009;13:60–69.
  • Kuo PC, Plotkin JS, Johnson LB, et al. Distinctive clinical features of portopulmonary hypertension. Chest. 1997;112:980–986.
  • Raevens S, Geerts A, Van Steenkiste C, et al. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int. 2015;35:1646–1660.
  • Jones FD, Kuo PC, Johnson LB, et al. The coexistence of portopulmonary hypertension and hepatopulmonary syndrome. Anesthesiology. 1999;90:626–629.
  • Ioachimescu OC, Mehta AC, Stoller JK. Hepatopulmonary syndrome following portopulmonary hypertension. Eur Respir J. 2007;29:1277–1280.
  • Pham DM, Subramanian R, Parekh S. Coexisting hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation. J Clin Gastroenterol. 2010;44:e136–e140.
  • Umeda A, Tagawa M, Kohsaka T, et al. Hepatopulmonary syndrome can show spontaneous resolution: possible mechanism of portopulmonary hypertension overlap? Respirology. 2006;11:120–123.
  • Benjaminov FS, Prentice M, Sniderman KW, et al. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut. 2003;52:1355–1362.
  • Pellicelli AM. Cytokines in portopulmonary hypertension. Gut. 2004;53:1721.
  • Pellicelli AM, Barbaro G, Puoti C, et al. Plasma cytokines and portopulmonary hypertension in patients with cirrhosis waiting for orthotopic liver transplantation. Angiology. 2010;61:802–806.
  • Sinzinger H. Prostacyclin in portopulmonary hypertension. Wien Klin Wochenschr. 2000;112:1020–1021.
  • Martinez-Palli G, Vidal JB, Beltran J, et al. Portopulmonary hypertension and hepatopulmonary syndrome: two different entities affecting pulmonary vasculature in liver disease. Crit Care Med. 2005;33:269.
  • Chavez-Tapia NC, Uribe M, Lopez E. Pulmonary complications of hepatic cirrhosis: portopulmonary hypertension and hepatopulmonary syndrome. The paradox of pulmonary vasoconstriction and vasodilation. Gac Med Mex. 2007;143:333–339.
  • Wong F. Portopulmonary hypertension in cirrhosis: the pathogenetic challenge. Gut. 2005;54:309.
  • Aldenkortt F, Aldenkortt M, Caviezel L, et al. Portopulmonary hypertension and hepatopulmonary syndrome. World J Gastroenterol. 2014;20:8072–8081.
  • Medarov BI, Chopra A, Judson MA. Clinical aspects of portopulmonary hypertension. Respir Med. 2014;108:943–954.
  • Bernthal AC, Eybel CE, Payne JA. Primary pulmonary hypertension after portocaval shunt. J Clin Gastroenterol. 1983;5:353–356.
  • Talwalkar JA, Swanson KL, Krowka MJ, et al. Prevalence of spontaneous portosystemic shunts in patients with portopulmonary hypertension and effect on treatment. Gastroenterology. 2011;141:1673–1679.
  • Khimji AK, Rockey DC. Endothelin-biology and disease. Cell Signal. 2010;22:1615–1625.
  • Shao D, Park JE, Wort SJ. The role of endothelin-1 in the pathogenesis of pulmonary arterial hypertension. Pharmacol Res. 2011;63:504–511.
  • Benigni A, Remuzzi G. Endothelin antagonists. Lancet. 1999;353:133–138.
  • Dupuis J. Endothelin-receptor antagonists in pulmonary hypertension. Lancet. 2001;358:1113–1114.
  • Halank M, Miehlke S, Hoeffken G, et al. Use of oral endothelin-receptor antagonist bosentan in the treatment of portopulmonary hypertension. Transplantation. 2004;77:1775–1776.
  • Tempe DK, Datt V, Datta D. Bosentan for the treatment of portopulmonary hypertension. Ann Card Anaesth. 2008;11:139–140.
  • Sallam M, Watson WC. Pulmonary hypertension due to micro-thromboembolism from splenic and portal veins after portacaval anastomosis. Br Heart J. 1970;32:269–271.
  • Edwards BS, Weir EK, Edwards WD, et al. Coexistent pulmonary and portal hypertension: morphologic and clinical features. J Am Coll Cardiol. 1987;10:1233–1238.
  • Robalino BD, Moodie DS. 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.
  • Robbins IM, Kawut SM, Yung D, et al. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension. Eur Respir J. 2006;27:578–584.
  • Nakonechnicov S, Gabbasov Z, Chazova I, et al. Platelet aggregation in patients with primary pulmonary hypertension. Blood Coagul Fibrinolysis. 1996;7:225–227.
  • Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992;327:70–75.
  • Maruyama T, Ohsaki K, Shimoda S, et al. Thromboxane-dependent portopulmonary hypertension. Am J Med. 2005;118:93–94.
  • Roberts KE, Fallon MB, Krowka MJ, et al. Genetic risk factors for portopulmonary hypertension in patients with advanced liver disease. Am J Respir Crit Care Med. 2009;179:835–842.
  • Girerd B, Coulet F, Jais X, et al. Characteristics of pulmonary arterial hypertension in affected carriers of a mutation located in the cytoplasmic tail of bone morphogenetic protein receptor type 2. Chest. 2015;147:1385–1394.
  • Maruyama H, Dewachter C, Belhaj A, et al. Endothelin-bone morphogenetic protein type 2 receptor interaction induces pulmonary artery smooth muscle cell hyperplasia in pulmonary arterial hypertension. J Heart Lung Transplant. 2015;34:468–478.
  • Kabata H, Satoh T, Kataoka M, et al. Bone morphogenetic protein receptor type 2 mutations, clinical phenotypes and outcomes of Japanese patients with sporadic or familial pulmonary hypertension. Respirology. 2013;18:1076–1082.
  • Castano G, Sookoian S. Female sex and autoimmune hepatitis and the risk of portopulmonary hypertension. Hepatology. 2008;48:2090.
  • 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.
  • Pilatis ND, Jacobs LE, Rerkpattanapipat P, et al. Clinical predictors of pulmonary hypertension in patients undergoing liver transplant evaluation. Liver Transpl. 2000;6:85–91.
  • Halank M, Langner S, Kolditz M, et al. Nocturnal oxygen desaturation is a frequent complication in portopulmonary hypertension. Z Gastroenterol. 2008;46:1260–1265.
  • Devaraj A, Loveridge R, Bosanac D, et al. Portopulmonary hypertension: improved detection using CT and echocardiography in combination. Eur Radiol. 2014;24:2385–2393.
  • Kim WR, Krowka MJ, Plevak DJ, et al. Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates. Liver Transpl. 2000;6:453–458.
  • 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.
  • Hua R, Sun YW, Wu ZY, et al. Role of 2-dimensional Doppler echo-cardiography in screening portopulmonary hypertension in portal hypertension patients. Hepatobiliary Pancreat Dis Int. 2009;8:157–161.
  • Auletta M, Oliviero U, Iasiuolo L, et al. Pulmonary hypertension associated with liver cirrhosis: an echocardiographic study. Angiology. 2000;51:1013–1020.
  • Ko JM, Ahn MI, Han DH, et al. Dynamic CT and MRA findings of a case of portopulmonary venous anastomosis (PPVA) in a patient with portal hypertension: a case report and review of the literature. Acta Radiol. 2011;52:566–569.
  • Krowka MJ. Portopulmonary hypertension: diagnostic advances and caveats. Liver Transpl. 2003;9:1336–1337.
  • Kawut SM, Taichman DB, Ahya VN, et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl. 2005;11:1107–1111.
  • Naeije R, Vachiery JL, Yerly P, et al. The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease. Eur Respir J. 2013;41:217–223.
  • Porres-Aguilar M, Mukherjee D. Cardiopulmonary hemodynamics for accurate diagnosis of portopulmonary hypertension: a redefinition to consider. Hepatology. 2015;61:733–734.
  • Krowka MJ. Portopulmonary hypertension and the issue of survival. Liver Transpl. 2005;11:1026–1027.
  • Saner FH, Nadalin S, Pavlakovic G, et al. Portopulmonary hypertension in the early phase following liver transplantation. Transplantation. 2006;82:887–891.
  • Swanson KL, Wiesner RH, Nyberg SL, et al. Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups. Am J Transplant. 2008;8:2445–2453.
  • Porres-Aguilar M, Altamirano JT, Torre-Delgadillo A, et al. Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview. Eur Respir Rev. 2012;21:223–233.
  • Savale L, O'Callaghan DS, Magnier R, et al. Current management approaches to portopulmonary hypertension. Int J Clin Pract Suppl. 2011;169:11–18.
  • Chan-Dominy AC, Rahiman SN, Anders M, et al. Extracorporeal membrane oxygenation and severe portopulmonary hypertension following liver transplantation: brief report. Int J Artif Organs. 2015;38:337–342.
  • Solik P, Lesny P, Luknar M, et al. The long-term response to treatment with calcium channel blockers in a patient with idiopathic pulmonary arterial hypertension. Bratisl Lek Listy. 2013;114:283–286.
  • Montani D, Savale L, Natali D, et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. Eur Heart J. 2010;31:1898–1907.
  • Ota K, Shijo H, Kokawa H, et al. Effects of nifedipine on hepatic venous pressure gradient and portal vein blood flow in patients with cirrhosis. J Gastroenterol Hepatol. 1995;10:198–204.
  • 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.
  • Huonker M, Schumacher YO, Ochs A, et al. Cardiac function and haemodynamics in alcoholic cirrhosis and effects of the transjugular intrahepatic portosystemic stent shunt. Gut. 1999;44:743–748.
  • Van der Linden P, Le Moine O, Ghysels M, et al. Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function. Hepatology. 1996;23:982–987.
  • DuBrock HM, Channick RN, Krowka MJ. What's new in the treatment of portopulmonary hypertension? Expert Rev Gastroenterol Hepatol. 2015;9:983–992.
  • Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351:1425–1436.
  • Ghofrani HA, Galie N, Grimminger F, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369:330–340.
  • Greig SL, Scott LJ, Plosker GL. Epoprostenol (Veletri®, Caripul®): a review of its use in patients with pulmonary arterial hypertension. Am J Cardiovasc Drugs. 2014;14:463–470.
  • Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med. 2010;104:9–21.
  • Safdar Z. Treatment of pulmonary arterial hypertension: the role of prostacyclin and prostaglandin analogs. Respir Med. 2011;105:818–827.
  • LeVarge BL. Prostanoid therapies in the management of pulmonary arterial hypertension. Ther Clin Risk Manag. 2015;11:535–547.
  • Lang IM, Gaine SP. Recent advances in targeting the prostacyclin pathway in pulmonary arterial hypertension. Eur Respir Rev. 2015;24:630–641.
  • Saito Y, Nakamura K, Akagi S, et al. Epoprostenol sodium for treatment of pulmonary arterial hypertension. Vasc Health Risk Manag. 2015;11:265–270.
  • Patel BB, Feng Y, Cheng-Lai A. Pulmonary arterial hypertension: a review in pharmacotherapy. Cardiol Rev. 2015;23:33–51.
  • Krowka MJ, Frantz RP, McGoon MD, 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.
  • Sussman N, Kaza V, Barshes N, et al. Successful liver transplantation following medical management of portopulmonary hypertension: a single-center series. Am J Transplant. 2006;6:2177–2182.
  • Fix OK, Bass NM, De Marco T, et al. Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl. 2007;13:875–885.
  • Awdish RL, Cajigas HR. Early initiation of prostacyclin in portopulmonary hypertension: 10 years of a transplant center's experience. Lung. 2013;191:593–600.
  • Plotkin JS, Kuo PC, Rubin LJ, et al. Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension. Transplantation. 1998;65:457–459.
  • Findlay JY, Plevak DJ, Krowka MJ, et al. Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension. Liver Transpl Surg. 1999;5:362–365.
  • Touma W, Nayak RP, Hussain Z, et al. Epoprostenol-induced hypersplenism in portopulmonary hypertension. Am J Med Sci. 2012;344:345–349.
  • Clapp LH, Gurung R. The mechanistic basis of prostacyclin and its stable analogues in pulmonary arterial hypertension: role of membrane versus nuclear receptors. Prostaglandins Other Lipid Mediat. 2015;120:56–71.
  • Minder S, Fischler M, Muellhaupt B, et al. Intravenous iloprost bridging to orthotopic liver transplantation in portopulmonary hypertension. Eur Respir J. 2004;24:703–707.
  • Molnar C, Alber H, Colleselli D, et al. Successful switch from inhalative iloprost to oral bosentan in portopulmonary hypertension associated with liver cirrhosis. Wien Klin Wochenschr. 2004;116:627–630.
  • Halank M, Marx C, Miehlke S, et al. Use of aerosolized inhaled iloprost in the treatment of portopulmonary hypertension. J Gastroenterol. 2004;39:1222–1223.
  • Hoeper MM, Seyfarth HJ, Hoeffken G, et al. Experience with inhaled iloprost and bosentan in portopulmonary hypertension. Eur Respir J. 2007;30:1096–1102.
  • Melgosa MT, Ricci GL, Garcia-Pagan JC, et al. Acute and long-term effects of inhaled iloprost in portopulmonary hypertension. Liver Transpl. 2010;16:348–356.
  • Kim EJ, Shin MS, Oh KY, et al. Successful management of portopulmonary hypertension with beraprost. Eur J Gastroenterol Hepatol. 2010;22:1503–1505.
  • Torres F, Rubin LJ. Treprostinil for the treatment of pulmonary arterial hypertension. Expert Rev Cardiovasc Ther. 2013;11:13–25.
  • Pugliese SC, Bull TM. Clinical use of extended-release oral treprostinil in the treatment of pulmonary arterial hypertension. Integr Blood Press Control. 2016;9:1–7.
  • Sitbon O, Channick R, Chin KM, et al. Selexipag for the treatment of pulmonary arterial hypertension. N Engl J Med. 2015;373:2522–2533.
  • Tapson VF, Torres F, Kermeen F, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients on background endothelin receptor antagonist and/or phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C study): a randomized controlled trial. Chest. 2012;142:1383–1390.
  • Tapson VF, Jing ZC, Xu KF, et al. Oral treprostinil for the treatment of pulmonary arterial hypertension in patients receiving background endothelin receptor antagonist and phosphodiesterase type 5 inhibitor therapy (the FREEDOM-C2 study): a randomized controlled trial. Chest. 2013;144:952–958.
  • Jing ZC, Parikh K, Pulido T, et al. Efficacy and safety of oral treprostinil monotherapy for the treatment of pulmonary arterial hypertension: a randomized, controlled trial. Circulation. 2013;127:624–633.
  • Scott LJ. Selexipag: first global approval. Drugs. 2016;76:413–418.
  • O'Connell C, Amar D, Boucly A, et al. Comparative safety and tolerability of prostacyclins in pulmonary hypertension. Drug Saf. 2016. [Epub ahead of print]. doi: 10.1007/s40264-015-0365-x.
  • Neuhofer W, Gulberg V, Gerbes AL. Endothelin and endothelin receptor antagonism in portopulmonary hypertension. Eur J Clin Invest. 2006;36 Suppl:54–61.
  • Maguire JJ, Davenport AP. Endothelin receptors and their antagonists. Semin Nephrol. 2015;35:125–136.
  • Miyagawa K, Emoto N. Current state of endothelin receptor antagonism in hypertension and pulmonary hypertension. Ther Adv Cardiovasc Dis. 2014;8:202–216.
  • Hoeper MM, Halank M, Marx C, et al. Bosentan therapy for portopulmonary hypertension. Eur Respir J. 2005;25:502–508.
  • Grander W, Eller P, Fuschelberger R, et al. Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis C. Eur J Clin Invest. 2006;36 Suppl:67–70.
  • Barth F, Gerber PJ, Reichen J, et al. Efficiency and safety of bosentan in child C cirrhosis with portopulmonary hypertension and renal insufficiency. Eur J Gastroenterol Hepatol. 2006;18:1117–1119.
  • Savale L, Magnier R, Le Pavec J, et al. Efficacy, safety and pharmacokinetics of bosentan in portopulmonary hypertension. Eur Respir J. 2013;41:96–103.
  • 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 Transpl. 2008;14:287–291.
  • Halank M, Kolditz M, Miehlke S, et al. Combination therapy for portopulmonary hypertension with intravenous iloprost and oral bosentan. Wien Med Wochenschr. 2005;155:376–380.
  • Eriksson C, Gustavsson A, Kronvall T, et al. Hepatotoxicity by bosentan in a patient with portopulmonary hypertension: a case-report and review of the literature. J Gastrointestin Liver Dis. 2011;20:77–80.
  • Galie N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013;62:D60–D72.
  • Cartin-Ceba R, Swanson K, Iyer V, et al. Safety and efficacy of ambrisentan for the treatment of portopulmonary hypertension. Chest. 2011;139:109–114.
  • Halank M, Knudsen L, Seyfarth HJ, et al. Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension. Z Gastroenterol. 2011;49:1258–1262.
  • Iglarz M, Binkert C, Morrison K, et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008;327:736–745.
  • Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369:809–818.
  • Cockrill BA, Waxman AB. Phosphodiesterase-5 inhibitors. Handb Exp Pharmacol. 2013;218:229–255.
  • Reichenberger F, Voswinckel R, Steveling E, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006;28:563–567.
  • Gough MS, White RJ. Sildenafil therapy is associated with improved hemodynamics in liver transplantation candidates with pulmonary arterial hypertension. Liver Transpl. 2009;15:30–36.
  • Hemnes AR, Robbins IM. Sildenafil monotherapy in portopulmonary hypertension can facilitate liver transplantation. Liver Transpl. 2009;15:15–19.
  • Fisher JH, Johnson SR, Chau C, et al. Effectiveness of phosphodiesterase-5 inhibitor therapy for portopulmonary hypertension. Can Respir J. 2015;22:42–46.
  • Hollatz TJ, Musat A, Westphal S, et al. Treatment with sildenafil and treprostinil allows successful liver transplantation of patients with moderate to severe portopulmonary hypertension. Liver Transpl. 2012;18:686–695.
  • Wang RC, Jiang FM, Zheng QL, et al. Efficacy and safety of sildenafil treatment in pulmonary arterial hypertension: a systematic review. Respir Med. 2014;108:531–537.
  • Yoshida EM, Erb SR, Pflugfelder PW, et al. Single-lung versus liver transplantation for the treatment of portopulmonary hypertension – a comparison of two patients. Transplantation. 1993;55:688–690.
  • Krowka MJ, Plevak DJ, Findlay JY, et al. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation. Liver Transpl. 2000;6:443–450.
  • Martin P, DiMartini A, Feng S, et al. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59:1144–1165.
  • Krowka MJ, Mandell MS, Ramsay MA, et al. Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database. Liver Transpl. 2004;10:174–182.
  • Khaderi S, Khan R, Safdar Z, et al. Long-term follow-up of portopulmonary hypertension patients after liver transplantation. Liver Transpl. 2014;20:724–727.
  • Ashfaq M, Chinnakotla S, Rogers L, et al. The impact of treatment of portopulmonary hypertension on survival following liver transplantation. Am J Transplant. 2007;7:1258–1264.
  • Goldberg DS, Batra S, Sahay S, et al. MELD exceptions for portopulmonary hypertension: current policy and future implementation. Am J Transplant. 2014;14:2081–2087.
  • Krowka MJ, Fallon MB, Mulligan DC, et al. Model for end-stage liver disease (MELD) exception for portopulmonary hypertension. Liver Transpl. 2006;12:S114–S116.
  • Krowka MJ, Wiesner RH, Heimbach JK. Pulmonary contraindications, indications and MELD exceptions for liver transplantation: a contemporary view and look forward. J Hepatol. 2013;59:367–374.
  • Pirenne J, Verleden G, Nevens F, et al. Combined liver and (heart-)lung transplantation in liver transplant candidates with refractory portopulmonary hypertension. Transplantation. 2002;73:140–142.
  • Grannas G, Neipp M, Hoeper MM, et al. Indications for and outcomes after combined lung and liver transplantation: a single-center experience on 13 consecutive cases. Transplantation. 2008;85:524–531.

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