Das hepatopulmonale Syndrom - Wo stehen wir im Jahr 2006?

Zusammenfassung

Das hepatopulmonale Syndrom (HPS) ist charakterisiert durch die Kombination einer Hepatopathie und der Störung des pulmonalen Gasaustausches mit arterieller Hypoxämie, intrapulmonaler Gefäßdilatation und Shuntbildung ohne zugrunde liegende kardiale oder pulmonale Erkrankung. Der Verlauf ist in der Regel progredient und das Mortalitätsrisiko in Abhängigkeit vom pulmonalarteriellen Shuntvolumen und dem Ausmaß der pO₂-Erniedrigung bei Raumluft zunehmend erhöht. Die Pathophysiologie des HPS ist bis dato nur partiell geklärt. Favorisiert wird eine multifaktorielle Genese. Neben funktionellen intrapulmonalen arteriovenösen Shunts, welche die wichtigste Ursache für das HPS darstellen, führen ein Ventilations-Perfusions-Ungleichgewicht sowie eine eingeschränkte Sauerstoffdiffusion zur Entwicklung einer arteriellen Hypoxämie. Klinisch gilt es zwischen pulmonalen und hepatischen Symptomen zu differenzieren. Diagnostisch ist vor allem die Kontrastmittelechokardiographie das Verfahren der Wahl. Symptomatisch kann die für das HPS charakteristische Hypoxämie durch Sauerstoffgabe gelindert werden. Der einzige in größeren Patientenkollektiven belegte erfolgreiche Behandlungsansatz des HPS ist die Lebertransplantation. Ziel der folgenden Übersicht ist deshalb eine Standortbestimmung.

Abstract

The hepatopulmonary syndrome (HPS) is characterized by a combination of liver disease and pulmonary gas exchange abnormalities with arterial hypoxemia, intrapulmonary vasodilatation and arteriovenous shunting in the absence of intrinsic cardiopulmonary disease. The course of the disease is typically progressive. The mortality rate correlates with the pulmonary shunt volume and the degree of hypoxemia at room air. While the pathyphysiology of HPS is still not fully understood, a multifactorial etiology is favored. Apart from functional intrapulmonary arteriovenous shunts which appear to represent a major factor in the development of HPS, both ventilation-perfusion mismatch and limited oxygen diffusion contribute to the HPS. Regarding its clinical appearance, pulmonary and hepatic symptoms have to be distinguished. Contrast echocardiography is the primary diagnostic tool. Symptomatically, hypoxemia can be treated with oxygen. So far, the only successful treatment approach which has been tested in larger patient groups, is liver transplantation. Given this background, the aim of this review is to critically discuss current concepts of this serious complication of liver diseases.

Schlüsselwörter

Hepatopathie - hepatopulmonales Syndrom - Hypoxämie - NO - pulmonale Vasodilatation

Key words

Hepatopathy - hepatopulmonary syndrome - hypoxemia - NO - pulmonary vasodilatation

Literatur

• 1 Rich S. Executive summary from the World Symposium on Primary Pulmonary Hypertension,. Evian, France; co-sponsored by The World Health Organization September 6 - 10, 1998
• 2 Rodríguez-Rosin R, Krowka M J, Hervé P h. et al . Pulmonary-Hepatic vascular disorders (PHD).  Eur Respir J. 2004;  24 861-880
• 3 Halank M, Miehlke S, Kolditz M. et al . Portopulmonale Hypertonie.  Z Gastroenterol. 2005;  43 677-685
• 4 Mandell M S. Critical care issues: portopulmonary hypertension.  Liver Transpl. 2000;  6 (4, Suppl 1) S36-43
• 5 Kim W R, Krowka M J, Plevak D J. et al . Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.  Liver Transpl. 2000;  6 453-458
• 6 Krowka M J. Portopulmonary hypertension: diagnostic advances and caveats.  Liver Transpl. 2003;  32 2177-2178
• 7 Kuo P C, Johnson L B, Plotkin J S. et al . Continous intravenous infusion of epoprostenol for the treatment of portopulmonary hpyertension.  Transplantation. 1997;  63 604-606
• 8 Krowka M J. Pulmonary hypertension, (high) risk of liver transplantation, and some lesions from „primary” pulmonary hypertension.  Liver Transpl. 2002;  8 389-390
• 9 Sood G, Fallon M B, Niwas S. et al . Utility of a dyspnea-fatigue index for screening liver transplant candidates for hepatopulmonary syndrome.  Hepatology. 1998;  28 2319 A
• 10 Fallon M B, Abrams G A. Pulmonary dysfunction in chronic liver disease.  Hepatology. 2000;  32 859-865
• 11 Cardenas A, Kelleher T, Chopra S. Review article: hepatic hydrothorax.  Alment Pharmacol Ther. 2004;  20 271-279
• 12 Krowka M J, Cortese D A. Hepatopulmonary syndrome. Current concepts in diagnostic and therapeutic considerations.  Chest. 1994;  105 1528-1537
• 13 Krowka M J, Dickson E R, Cortese D A. Hepatopulmonary syndrome: clinical observations and lack of therapeutic response to somatostatin analogue.  Chest. 1993;  104 515-521
• 14 Naeije R. Hepatopulmonary syndrome and portopulmonary hypertension.  Swiss Med Wkly. 2003;  133 163-169
• 15 Scott V L, Dodson S F, Kang Y. The hepatopulmonary syndrome.  Surg Clin North Am. 1999;  79 23-41
• 16 Rydell R, Hoffbauer F W. Multiple pulmonary arteriovenous fistulas in juvenile cirrhosis.  Am J Med. 1956;  21 450-459
• 17 Kennedy T C, Knudson R J. Exercise-aggravated hypoxemia and orthodeoxia in cirrhosis.  Chest. 1977;  72 305-309
• 18 Kaymakoglu S, Kahraman T, Kudat H. et al . Hepatopulmonary syndrome in noncirrhotic portal hypertensive patients.  Dig Dis Sci. 2003;  48 556-560
• 19 Teuber G, Teupe C, Dietrich C F. et al . Pulmonary dysfunction in non-cirrhotic patients with chronic viral hepatitis.  Eur J Intern Med. 2002;  13 311-318
• 20 Gupta D, Vijaya D R, Gupta R. et al . Prevalence of hepatopulmonary syndrome in cirrhosis and extrahepatic portal venous obstruction.  Am J Gastroenterol. 2001;  96 3395-3399
• 21 Binay K, Sen S, Biswas P K. et al . Hepatopulmonary syndrome in inferior vena cava obstruction responding to cavoplasty.  Gastroenterology. 2000;  118 192-196
• 22 BK, Sen S, Biswas P K. et al . Occurrence of hepatopulmonary syndrome in Budd-Chiari syndrome and the role of venous decompression.  Gastroenterology. 2002;  122 897-903
• 23 Regev A, Yeshurun M, Rodriguez M. et al . Transient hepatopulmonary syndrome in a patient with acute hepatitis A.  J Viral Hepatol. 2001;  8 83-86
• 24 Maggiore G, Borgna-Pignati C, Marni E. Pulmonary arteriovenous fistulas: an unusual complication of congenital hepatic fibrosis.  J Pediatr Gastroenterol Nutr. 1983;  2 183-186
• 25 Hobeika J, Houssin D, Bernard O. et al . Orthotopic liver transplantation in children with chronic liver disease and severe hypoxemia.  Transplantation. 1994;  57 224-228
• 26 Krowka M J. Post-OLT for HPS: a light at the end of the tunnel.  Transplantation. 2003;  75 1446-1447
• 27 Cremona G, Higenbottam T W, Mayoral V. et al . Elevated exhaled nitric oxide in patients with hepatopulmonary syndrome.  Eur Respir J. 1995;  8 1883-1885
• 28 Martinez-Palli G, Barberà J A, Visa J. et al . Hepatopulmonary syndrome: prevalence and clininal markers.  Eur Respir J. 1996;  9 179 s
• 29 Rolla G, Brussino L, Colagrande P. Exhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation.  Ann Int Med. 1998;  129 375-378
• 30 Rolla G, Brussino L, Colagrande P. et al . Exhaled nitric oxide and oxgenation abnormalities in hepatic cirrhosis.  Hepatology. 1997;  26 842-847
• 31 Fallon M B, Abrams G A, 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
• 32 Nunes H, Lebrec D, Mazmanian M. et al . Role of nitric oxide in hepatopulmonary syndrome in cirrhotic rats.  Am J Respir Crit Care Med. 2001;  164 879-885
• 33 Khoruts A, Stahnke L, McClain C J. et al . Circulating tumor necrosis factor, interleukin-1 and interleukin-6 concentrations in chronic alcoholic patients.  Hepatology. 1991;  13 267-276
• 34 Rabiller A, Nunes H, Lebrec D. et al . Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome.  Am J Respir Crit Care Med. 2002;  166 514-517
• 35 Luo B, Liu L, Tang L. et al . 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;  38 556-563
• 36 Kuchan M, Jo H, Frangos J. Role of G proteins in shear stress-mediated nitric oxide production by endothelial cells.  Am J Physiol. 1994;  267 C753-758
• 37 Carter E P, Hartsfield C L, Miyazono M. et al . Regulation of heme oxygenase-1 by nitric oxide during hepatopulmonary syndromel.  Am J Physiol Lung Cell Mol Physiol. 2002;  283 L346-353
• 38 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 1441-1451
• 39 Fernandez M, Vizzutti F, Garcia-Pagan J C. et al . Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice.  Gastroenterology. 2004;  126 886-894
• 40 Krowka M J, Cortese D A. Pulmonary aspects of chronic liver disease and liver transplantation.  Mayo Clin Proc. 1985;  60 407-418
• 41 Krowka M J. Hepatopulmonary syndromes.  Gut. 2000;  46 1-4
• 42 Fallon M B, Abrams G A. Pulmonary dysfunction in chronic liver disease.  Hepatology. 2000;  32 859-865
• 43 Aboussouan L S, Stoller J K. The hepatopulmonary syndrome.  Baillière’s Clin Gastroenterol. 2000;  14 1033-1048
• 44 Hoeper M M, Krowka M J, Strassburg C P. Portopulmonary hypertension and hepatopulmonary syndrome.  Lancet. 2004;  363 1461-1468
• 45 Martínez G P, Barberà J A, Visa J. et al . Hepatopulmonary syndrome in candidates for liver transplantation.  J Hepatol. 2001;  34 651-657
• 46 Aller R, Moya J L, Moreira V. et al . Diagnosis of hepatopulmonary syndrome with contrast transesophageal echocardiography.  Dig Dis Sci. 1999;  44 1243-1248
• 47 Hind C R, Wong C M. Detection of pulmonary arteriovenous fistulae in patient with cirrhosis by contrast 2D echocardiography.  Gut. 1981;  22 1042-1045
• 48 Mimidis K P, Vassilakos P I, Mastorakou A N. et al . Evaluation of contrast echocardiography and lung perfusion scan in detecting intrapulmonary vascular dilatation in normoxemic patients with early liver cirrhosis.  Hepatogastroenterology. 1998;  45 2303-2307
• 49 Abrams G, Nanda N, Dubovsky E. et al . Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach.  Gastroenterology. 1998;  114 305-310
• 50 Krowka M J, Wiseman G A, Burnett O L. et al . Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100 % oxgen, and brain uptake after (99 m)TC MAA lung scanning.  Chest. 2000;  118 615-624
• 51 Abrams G A, Krowka M J, Fallon M B. Prospective evaluation of outcomes and predictors or mortality in patients undergoing liver transplantation for hepatopulmonary syndrome.  Hepatology. 2003;  37 192-197
• 52 Lee K N, Lee H J, Shin W W. et al . Hypoxemia and liver cirrhosis (hepatopulmonary syndrome) in eight patients: comparison of the central and peripheral pulmonary vasculature.  Radiology. 1999;  211 549-553
• 53 Schenk P, Schöniger-Hekele M, Fuhrmann V. et al . Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis.  Gastroenterology. 2003;  125 1042-1052
• 54 Andrivet P, Cadranel J, Housset B. et al . Mechanisms of impaired arterial oxygenation in patients with liver cirrhosis and severe respiratory insufficiency. Effects of indomethacin.  Chest. 1993;  103 500-507
• 55 Castro M, Krowka M J. Hepatopulmonary syndrome. A pulmonary vascular complication of liver disease.  Clin Chest Med. 1996;  17 35-48
• 56 Shijo H, Sasaki H, Yuh K. et al . Effects of indomethacin on hepatogenic pulmonary dysplasia.  Chest. 1991;  99 1027-1029
• 57 Wolfe J D, Tashkin D P, Holly F E. et al . Hypoxemia of cirrhosis: Detection of abnormal small pulmonary vascular channels by a quantitative radionuclide method.  Am J Med. 1977;  63 746-754
• 58 Agusti A G, Roca J, Bosch J. et al . Effects of propanolol on arterial oxygenation and oxygen transport to tissues in patients with cirrhosis.  Am Rev Respir Dis. 1990;  142 306-310
• 59 Krowka J M, Cortese D A. Severe hypoxemia associated with liver disease: Mayo Clinic experience and the experimental use of almitrine bismesylate.  Mayo Clin Proc. 1987;  62 164-173
• 60 Abrams G A, Fallon M B. Treatment of hepatopulmonary syndrome with Allium sativum L. (garlic): a pilot trial.  J Clin Gastroenterol. 1998;  27 232-235
• 61 Niederberger M, Martin P Y, Gines P. et al . Normalization of nitric oxide production corrects arterial vasodilation and hyperdynamic circulation in cirrhotic rats.  Gastroenterology. 1995;  109 1624-1630
• 62 Schenk P, Madl C, Rezaie-Majd S. et al . Methylene blue improves the hepatopulmonary syndrome.  Ann Intern Med. 2000;  133 701-706
• 63 Marzcin N, Ryan U S, Catravas J D. Methylene blue inhibits nitrovasodilator- and endothelium-derived relaxing factor-induced cyclic GMP accumulation in cultured pulmonary arterial smooth muscle cells via generation of superoxide anion.  J Pharmacol Exp Ther. 1992;  263 170-179
• 64 Sztrymf B, Rabiller A, Nunes H. et al . Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats.  Eur Respir J. 2004;  23 752-758
• 65 Anel R ML, Sheagren J N. Novel presentation and approach to management of hepatopulmonary syndrome with the use of antimicrobial agents.  Clin Infect Dis. 2001;  32 131-136
• 66 Krowka M J, Cortese D A. Pulmonary aspects of liver disease and liver transplantation.  Clin Chest Med. 1989;  10 593-616
• 67 Rolla G, Brussino L, Dutto L. et al . Smoking and hypoxemia caused by hepatopulmonary syndrome before and after liver transplantation.  Hepatology. 2001;  34 430-431
• 68 Allgaier H, Haag K, Ochs A. et al . Hepatopulmonary syndrome. Successful treatment by transjugular portosystemic stent-shunt (TIPS).  J Hepatol. 1995;  23 102
• 69 Corley D A, Scharschmidt B, Bass N. et al . Lack of efficacy of TIPS for hepatopulmonary syndrome.  Gastroenterology. 1997;  113 728-731
• 70 Riegler J L, Lang K A, Johnson S P. et al . Transjugular intrahepatic portosystemic shunt improves oxygenation in hepatopulmonary syndrome.  Gastroenterology. 1995;  109 978-983
• 71 Selim K M, Akriviadis E A, Zuckerman E. et al . Transjugular intrahepatic portosystemic shunt: a successful treatment for hepatopulmonary syndrome.  Am J Gastroenterol. 1998;  93 455-458
• 72 Paramesh A S, Husain S Z, Shneider B. et al . Improvement of hepatopulmonary syndrome after transjugular intrahepatic portosystemic shunting: a case report and review of literature.  Pediatr Transplant. 2003;  7 157-162
• 73 Lasch H M, Fried M W, Zacks S L. et al . Use of transjugular intrahepatic portosystemic shunt as a bridge to liver transplantation in a patient with severe hepatopulmonary syndrome.  Liver Transpl. 2001;  7 147-149
• 74 Felt R W, Kozak B E, Rosch J. et al . Hepatogenic pulmonary angiodysplasia treated with coil-spring embolization.  Chest. 1987;  91 920-922
• 75 Ryu J K, Oh J H. Hepatopulmonary syndrome. Angiography and therapeutic embolization.  J Clin Imag. 2003;  27 97-100
• 76 Swanson K L, Wiesner R H, Krowka M J. Natural history of hepatopulmonary syndrome: impact of liver transplantation.  Hepatology. 2005;  41 1122-1129
• 77 Krowka J M. Hepatopulmonary syndrome: recent literature (1997 - 1999) and implications for liver transplantation.  Liver Transpl. 2000;  6 S31-35
• 78 Van Thiel D H, Schade R R, Gavaler J S. et al . Medical aspects of liver transplantation.  Hepatology. 1984;  4 79S-83S
• 79 Taillé C, Cadranel J, Bellocq A. et al . Liver transplantation for hepatopulmonary syndrome: a ten-year experience in Paris, France.  Transplantation. 2003;  79 1482-1489
• 80 Collisson E A, Nourmand H, Fraiman M H. et al . Retrospective analysis of the results of liver transplantation for adults with severe hepatopulmonary syndrome.  Liver Transpl. 2002;  8 925-931
• 81 Wiesner R, Edwards E, Freeman R. et al . Model for end-stage liver disease (MELD) and allocation of donor livers.  Gastroenterology. 2003;  124 91-96
• 82 Battaglia S E, Pretto J J, Irving L B. et al . Resolution of gas exchange abnormalities and intrapulmonary shunting following liver transplantation.  Hepatology. 1997;  25 1228-1232
• 83 Krowka M J, Porayko M K, Plevak D J. et al . Hepatopulmonary syndrome with progressive hypoxemia as an indication for liver transplantation: case reports and literature review.  Mayo Clin Proc. 1997;  72 44-52
• 84 Lange P A, Stoller J K. The hepatopulmonary syndrome: effect of liver transplantation.  Clin Chest Medicine. 1996;  17 115-124
• 85 Arguedas M R, Abrams G A, Krowka M J. et al . Prospektive evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation.  Hepatology. 2003;  37 192-197
• 86 Egawa H, Kasahara M, Inomata Y. et al . Long-term outcome of living related liver transplantation for patients with intrapulmonary shunting and strategy for complications.  Transplantation. 1999;  67 712-717
• 87 Itasaka H, Hershon J J, Cox K L. et al . Transient deterioration of intrapulmonary shunting after pediatric liver transplantation.  Transplantation. 1993;  55 212-214
• 88 Uemoto S, Inomata Y, Egawa H. et al . Effects of hypoxemia on early postoperative course of liver transplantation in pediatric patients with intrapulmonary shunting.  Transplantation. 1997;  63 407-414
• 89 Alexander J, Greenough A, Baker A. et al . Nitric oxide treatment of severe hypoxemia after liver transplantation in hepatopulmonary syndrome: case report.  Liver Transpl Surg. 1997;  3 54-55
• 90 Durand P h, Baujard C, Grose A L. et al . Reversal of hypoxemia by inhaled nitric oxide in children with severe hepatopulmonary syndrome, Type 1, during and after liver transplantation.  Transplantation. 1998;  65 437-439
• 91 Taniai N, Onda M, Tajiri T. et al . Reversal of hypoxemia by inhaled nitric oxide in a child with hepatopulmonary syndrome after living-related liver transplantation.  Transplant Proc. 2002;  34 2791-2792
• 92 Krowka M J, Wiseman G A, Steers J L. et al . Late recurrence and rapid evolution of severe hepatopulmonary syndrome after liver transplantation.  Liver Transpl Surg. 1999;  5 451-453
• 93 Avendano C E, Flume P A, Baliga P. et al . Hepatopulmonary syndrome occuring after orthotopic liver transplantation.  Liver Transpl. 2001;  7 1081-1084