Zusammenfassung
Die portopulmonale Hypertonie ist eine seltene Erkrankung, die durch das Vorhandensein eines erhöhten mittleren pulmonalarteriellen Druckes und dem gleichzeitigen Vorliegen einer portalen Hypertonie gekennzeichnet ist. Eine schwere portopulmonale Hypertonie gilt als Kontraindikation zur Durchführung einer Lebertransplantation. Zahlreiche Medikamente wie Prostazyklindrivate, Phosphodiesteraseinhibitoren wie auch duale Endothelinrezeptorantagonisten wurden in einzelnen Patienten versuchsweise eingesetzt. Die Wirkung eines selektiven Endothelinrezptorantagonisten wie Sitaxentan in diesem Kontext war bisher unbekannt. Wir berichten hier über die erfolgreiche Therapie mit oralem Sitaxentan über einen Zeitraum von drei Monaten, wobei sich sowohl die Leistungsfähigkeit wie auch die pulmonale Hämodynamik verbesserten. Zusätzlich kam es zu einer Verbesserung der portalen Hypertonie durch eine signifikanten Reduktion des Lebervenendruckes von 12 auf 8 mmHg. Der Einsatz selektiver Endothelinrezeptorantagonisten könnte somit eine neue Therapieoption für diese Patienten darstellen.
Summary
Portopulmonary hypertension (POPH) is a rare complication of portal hypertension. Prostanoids have been shown to be effective in the treatment of POPH and have been used as a bridge to liver transplantation. More recently, case series revealed beneficial effects of both the dual endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil. The efficacy of sitaxentan, a selective endothelin receptor A (ERA) antagonist in the reversal of POPH, is still unclear. We report a case of POPH that was successfully treated with oral sitaxentan. Haemodynamic and symptomatic improvements were maintained after a 12-week long-term treatment period. Additionally, hepatic vein pressure gradient significantly decreased from 12 mmHg to 8 mm after treatment with sitaxentan. This is the first reported case of a successful therapy with a selective ERA antagonist in a patient suffering from POPH. Oral sitaxentan therapy might be a promising new option for patients suffering from POPH.
This is a preview of subscription content, log in via an institution to check access.
References
Naeije R. Hepatopulmonary syndrome and portopulmonary hypertension. Swiss Medical Wkly 2003;133:163–9
Plotkin JS, Kuo PC, Rubin LJ, Gaine S, Howell CD, Laurin J, et al. Successful use of chronic epoprostenol as a bridge to liver transplantation in severe portopulmonary hypertension. Transplantation 1998;65:457–9
Budhiraja R, Hassoun PM. Portopulmonary hypertension: a tale of two circulations. Chest 2003;123:562–76
Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology 2006;44:1502–10
Herve P, Lebrec D, Brenot F, Simonneau G, Humbert M, Sitbon O, et al. Pulmonary vascular disorders in portal hypertension. Eur Respir J 1998;11:1153–66
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;17:492–8
Kahler CM, Graziadei I, Wiedermann CJ, Kneussl MP, Vogel W. Successful use of continuous intravenous prostacyclin in a patient with severe portopulmonary hypertension. Wien Klin Wochenschr 2000;112:637–40
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;30:641–8
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;63:604–6
Schroeder RA, Rafii AA, Plotkin JS, Johnson LB, Rustgi VK, Kuo PC. Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary hypertension. Transplantation 2000;70:548–50
Reichenberger F, Voswinckel R, Steveling E, Enke B, Kreckel A, Olschewski H, et al. Sildenafil treatment for portopulmonary hypertension. Eur Respir J 2006;28:563–7
Hoeper MM, Halank M, Marx C, Hoeffken G, Seyfarth HJ, Schauer J, et al. Bosentan therapy for portopulmonary hypertension. Eur Respir J 2005;25:502–8
Molnar C, Alber H, Colleselli D, Vogel W, Kähler CM. Successful switch from inhalative iloprost to oral bosentan in portopulmonary hypertension associated with liver cirrhosis. Wien Klin Wochenschr 2004;116:627–30
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;130:120–6
Barst RJ. Sitaxsentan: a selective endothelin-A receptor antagonist, for the treatment of pulmonary arterial hypertension. Expert Opin Pharmacother 2007;8:95–109
Ramsay MA, Simpson BR, Nguyen AT, Ramsay KJ, East C, Klintmalm GB. Severe pulmonary hypertension in liver transplant candidates. Liver Transpl Surg 1997;3:494–500
De Wolf AM, Scott VL, Gasior T, Kang Y. Pulmonary hypertension and liver transplantation. Anesthesiology 1993;78:213–4
Mandell MS, Groves BM. Pulmonary hypertension in chronic liver disease. Clin Chest Med 1996;17:17–33
Benjaminov FS, Prentice M, Sniderman KW, Siu S, Liu P, Wong F. Portopulmonary hypertension in decompensated cirrhosis with refractory ascites. Gut 2003;52:1355–62
Kuo PC, Plotkin JS, Gaine S, Schroeder RA, Rustgi VK, Rubin LJ, et al. Portopulmonary hypertension and the liver transplant candidate. Transplantation 1999;67:1087–93
Rodriguez-Roisin R, Krowka MJ, Herve P, Fallon MB. Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J 2004;24:861–80
Fix OK, Bass NM, De Marco T,Merriman RB. Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl 2007;13:875–85
Hoeper MM, Seyfarth HJ, Hoeffken G, Wirtz H, Spiekerkoetter E, Pletz MW, et al. Experience with inhaled iloprost and bosentan in portopulmonary hypertension. Eur Respir J 2007;30:1096–102
Wang YW, Lin HC, Yang YY, Hou MC, Lee SD. Sildenafil decreased pulmonary arterial pressure but may have exacerbated portal hypertension in a patient with cirrhosis and portopulmonary hypertension. J Gastroenterol 2006;41:593–7
Finley DS, Lugo B, Ridgway J, Teng W, Imagawa DK. Fatal variceal rupture after sildenafil use: report of a case. Curr Surg 2005;62:55–6
Tzathas C, Christidou A, Ladas SD. Sildenafil (viagra) is a risk factor for acute variceal bleeding. Am J Gastroenterol 2002;97:1856
Bremer HC, Kreisel W, Roecker K, Dreher M, Koenig D, Kurz-Schmieg AK, et al. Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension. A case report. J Med Case Rep 2007;1:46
Gerbes AL, Moller S, Gulberg V, Henriksen JH. Endothelin-1 and -3 plasma concentrations in patients with cirrhosis: role of splanchnic and renal passage and liver function. Hepatology 1995;21:735–9
Nagasue N, Dhar DK, Yamanoi A, Emi Y, Udagawa J, Yamamoto A, et al. Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis. Hepatology 2000;31:1107–14
Halank M, Ewert R, Seyfarth HJ, Hoeffken G. Portopulmonary hypertension. J Gastroenterol 2006;41:837–47
Hinterhuber L, Graziadei IW, Kahler CM, Jaschke W, Vogel W. Endothelin-receptor antagonist treatment of portopulmonary hypertension. Clin Gastroenterol Hepatol 2004;2:1039–42
Halank M, Miehlke S, Hoeffken G, Schmeisser A, Schulze M, Strasser RH. Use of oral endothelin-receptor antagonist bosentan in the treatment of portopulmonary hypertension. Transplantation 2004;77:1775–6
Leivas A, Jimenez W, Bruix J, Boix L, Bosch J, Arroyo V, et al. Gene expression of endothelin-1 and ET(A) and ET(B) receptors in human cirrhosis: relationship with hepatic hemodynamics. J Vasc Res 1998;35:186–93
Humbert M, Segal ES, Kiely DG, Carlsen J, Schwierin B, Hoeper MM. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J 2007;30:338–44
Barst RJ, Langleben D, Badesch D, Frost A, Lawrence EC, Shapiro S, et al. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006;47:2049–56
Tripathi D, Therapondos G, Ferguson JW, Newby DE, Webb DJ, Hayes PC. Endothelin-1 contributes to maintenance of systemic but not portal haemodynamics in patients with early cirrhosis: a randomised controlled trial. Gut 55: 2006;1290–5
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kähler, C., Graziadei, I., Vogelsinger, H. et al. Successful treatment of portopulmonary hypertension with the selective endothelin receptor antagonist Sitaxentan. Wien Klin Wochenschr 123, 248–252 (2011). https://doi.org/10.1007/s00508-011-1540-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00508-011-1540-4