Intensivmedizin und Notfallmedizin

, Volume 46, Issue 5, pp 347–354 | Cite as

Möglichkeiten und Zukunftsperspektiven der Leberersatztherapie

Leberunterstützungstherapien – Wo stehen wir heute?
  • A. Al-Chalabi
  • B. Kreymann
  • J. Langgartner
  • T. Brünnler
Innovationen in der Intensivmedizin

Zusammenfassung

Obgleich beispielsweise zum Lungen- oder Nierenersatz Verfahren im klinischen Alltag etabliert werden konnten, fehlt für die Leber eine entsprechend geeignete Technik, um Patienten mit Leberausfall entweder bis zur Regeneration des eigenen Organs oder bis zur Transplantation überbrückend behandeln zu können. Weder erscheinen, basierend auf der derzeitigen Literaturlage, die Patientenkollektive ausreichend charakterisiert, noch ist klar definiert, welche grundsätzlichen, quantitativen Funktionen Leberunterstützungssysteme erfüllen müssen. Eine Validierung der wichtigsten Systemparameter wie Blutfluss, Antikoagulation und die Auswirkungen auf die Biokompatibilität fehlt. Bei den derzeit in Erprobung befindlichen oder kommerziell erhältlichen Systemen können 3 Arten unterschieden werden: 1. die Plasmapherese (z. B. SEPET® System der Firma Arbios), 2. Entgiftungsverfahren wie die Albumindialyse [z. B. MARS® (Gambro oder SPAD)] oder das Prometheus® System (Fresenius) und 3. zellbasierte, meist mit einer zusätzlichen Entgiftungseinheit versehene Bioreaktoren (z. B. ELAD® System der Firma Vital therapy). Anhand der derzeitigen Literatur erscheinen die gängigen Verfahren insbesondere im Hinblick auf Detoxifikation mit klinischer Verbesserung von Patienten mit hepatischer Enzephalopathie geeignet. Aussagen zur Effektivität des Leberersatzes bezüglich der Reduktion der Mortalität fehlen bislang, dennoch dürften die Daten von 2 großen, derzeit noch laufenden multizentrischen Studien, die die Veränderungen der Mortalität als Endpunkt haben (Relief II, MARS-System, und Helios, Prometheus-System) darüber Auskunft geben.

Schlüsselwörter

Leberunterstützungstherapie Leberdialyse Antikoagulation Plasmapherese Albumindialyse 

Liver support systems

Where are we today?

Abstract

Despite existing procedures to replace lung or renal function in everyday clinical routine, an equivalent method to replace liver function is still missing to bridge patients to regenerate liver function or until transplantation. At the moment, neither the patient groups who would profit from such therapies nor the characteristics of the liver replacement therapy itself seem to be clear. Evaluation of the most important systemic parameters like blood flow, anticoagulation, and influence on biocompatibility are missing. Currently there are three main types of liver support systems: (1) plasmapheresis, e.g., SEPET® (Arbios); (2) artificial detoxification systems, e.g., albumin dialysis (MARS® (Gambro) or SPAD), and Prometheus® (Fresenius); (3) bioartificial detoxification systems where hepatocytes are used in bioreactors to compensate for liver function. Based on the current literature, the commonly used systems, especially with regard to detoxification, seem to be useful in the treatment of patients with hepatic encephalopathy. At present, there is no evidence that treatment with the commercially available liver support systems can improve survival in patients with liver failure. Two large multi-center studies are being performed for MARS (Relief II) and Prometheus (Helios), which will hopefully answer these questions.

Keywords

Liver support systems Anticoagulation Plasmapheresis Albumin dialysis 

Literatur

  1. 1.
    Amanzadeh J, Reilly RF Jr (2006) Anticoagulation and continuous renal replacement therapy. Semin Dial 19:311–3116PubMedGoogle Scholar
  2. 2.
    Bachli EB, Schuepbach RA, Maggiorini M et al (2007) Artificial liver support with the molecular adsorbent recirculating system: activation of coagulation and bleeding complications. Liver Int 27:475–484PubMedCrossRefGoogle Scholar
  3. 3.
    Clemmesen JO, Kondrup J, Nielsen LB et al (2001) Effects of high-volume plasmapheresis on ammonia, urea and amino acids in patients with acute liver failure. Am J Gastroenterol 96:1217–1223PubMedCrossRefGoogle Scholar
  4. 4.
    Clemmesen JO, Larsen FS, Ejlersen E et al (1997) Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure. Eur J Gastroenterol Hepatol 9:55–60PubMedGoogle Scholar
  5. 5.
    Davenport A, Will EJ, Davison AM (1991) Adverse effects on cerebral perfusion of prostacyclin administered directly into patients with fulminant hepatic failure and acute renal failure. Nephron 59:449–454PubMedCrossRefGoogle Scholar
  6. 6.
    Davenport A, Will EJ, Davison AM (1991) The effect of prostacyclin on intracranial pressure in patients with acute hepatic and renal failure. Clin Nephrol 35:151–157PubMedGoogle Scholar
  7. 7.
    Doria C, Mandala L, Smith JD et al (2004) Thromboelastography used to assess coagulation during treatment with molecular adsorbent recirculating system. Clin Transplant 18:365–371PubMedCrossRefGoogle Scholar
  8. 8.
    Doria C, Marino IR (2005) Bacteremia using the molecular adsorbent recirculating system in patients bridged to liver transplantation. Exp Clin Transplant 3:289–292PubMedGoogle Scholar
  9. 9.
    Evenepoel P, Laleman W, Wilmer A et al (2006) Prometheus versus molecular adsorbents recirculating system: comparison of efficiency in two different liver detoxification devices. Artif Organs 30:276–284PubMedCrossRefGoogle Scholar
  10. 10.
    Evenepoel P, Maes B, Wilmer A et al (2003) Detoxifying capacity and kinetics of the molecular adsorbent recycling system. Contribution of the different inbuilt filters. Blood Purif 21:244–252PubMedCrossRefGoogle Scholar
  11. 11.
    Faybik P, Bacher A, Kozek-Langenecker SA et al (2006) Molecular adsorbent recirculating system and hemostasis in patients at high risk of bleeding: an observational study. Crit Care 10:R24PubMedCrossRefGoogle Scholar
  12. 12.
    Fischer KG (2007) Essentials of anticoagulation in hemodialysis. Hemodial Int 11:178–189PubMedCrossRefGoogle Scholar
  13. 13.
    Heemann U, Treichel U, Loock J et al (2002) Albumin dialysis in cirrhosis with superimposed acute liver injury: a prospective, controlled study. Hepatology 36:949–958PubMedGoogle Scholar
  14. 14.
    Hessel F, Grabein K, Schnell-Inderst P et al (2006) Extrakorporale artifizielle Leberunterstützungssysteme bei akutem Leberversagen oder einer akuten Dekompensation eines chronischen Leberleidens, DIMDI (Deutsche Agentur für Health Technology Assessment)Google Scholar
  15. 15.
    Iwai H, Nagaki M, Naito T et al (1998) Removal of endotoxin and cytokines by plasma exchange in patients with acute hepatic failure. Crit Care Med 26:873–876PubMedCrossRefGoogle Scholar
  16. 16.
    Iwata H, Ueda Y (2004) Pharmacokinetic considerations in development of a bioartificial liver. Clin Pharmacokinet 43:211–125PubMedCrossRefGoogle Scholar
  17. 17.
    Jalan R, Sen S, Steiner C et al (2003) Extracorporeal liver support with molecular adsorbents recirculating system in patients with severe acute alcoholic hepatitis. J Hepatol 38:24–31PubMedCrossRefGoogle Scholar
  18. 18.
    Kiley JE, Welch HF, Pender JC, Welch CS (1956) Removal of blood ammonia by hemodialysis. Proc Soc Exp Biol Med 91:489–490PubMedGoogle Scholar
  19. 19.
    Kondrup J, Almdal T, Vilstrup H, Tygstrup N (1992) High volume plasma exchange in fulminant hepatic failure. Int J Artif Organs 15:669–676PubMedGoogle Scholar
  20. 20.
    Kramer L, Bauer E, Joukhadar C et al (2003) Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med 31:2450–2455PubMedCrossRefGoogle Scholar
  21. 21.
    Kreymann B, Seige M, Schweigart U et al (1999) Albumin dialysis: effective removal of copper in a patient with fulminant wilson disease and successful bridging to liver transplantation: a new possibility for the elimination of protein-bound toxins. J Hepatol 31:1080–1085PubMedCrossRefGoogle Scholar
  22. 22.
    Kuntz E, Kuntz H-D (2006) Hepatology: principles and practice. Springer, WürzburgGoogle Scholar
  23. 23.
    Laleman W, Wilmer A, Evenepoel P et al (2006) Effect of the molecular adsorbent recirculating system and Prometheus devices on systemic haemodynamics and vasoactive agents in patients with acute-on-chronic alcoholic liver failure. Crit Care 10:R108PubMedCrossRefGoogle Scholar
  24. 24.
    Lepore MJ, Martel AJ (1967) Plasmapheresis in hepatic coma. Lancet 2:771–772CrossRefGoogle Scholar
  25. 25.
    Meijers BK, Verhamme P, Nevens F et al (2007) Major coagulation disturbances during fractionated plasma separation and adsorption. Am J Transplant 7:2195–2199PubMedCrossRefGoogle Scholar
  26. 26.
    Mitzner SR, Stange J, Klammt S et al (2000) Improvement of hepatorenal syndrome with extracorporeal albumin dialysis MARS: results of a prospective, randomized, controlled clinical trial. Liver Transpl 6:277–286PubMedCrossRefGoogle Scholar
  27. 27.
    Nakae H, Igarashi T, Tajimi K (2006) The dose of nafamostat mesilate during plasma exchange with continuous hemodiafiltration in the series-parallel circuit. Ther Apher Dial 10:233–236PubMedCrossRefGoogle Scholar
  28. 28.
    Onodera K, Sakata H, Yonekawa M, Kawamura A (2006) Artificial liver support at present and in the future. J Artif Organs 9:17–28PubMedCrossRefGoogle Scholar
  29. 29.
    Rifai K, Ernst T, Kretschmer U et al (2003) Prometheus–a new extracorporeal system for the treatment of liver failure. J Hepatol 39:984–990PubMedCrossRefGoogle Scholar
  30. 30.
    Rozga J, Umehara Y, Trofimenko A et al (2006) A novel plasma filtration therapy for hepatic failure: preclinical studies. Ther Apher Dial 10:138–144PubMedCrossRefGoogle Scholar
  31. 31.
    Sadahiro T, Hirasawa H, Oda S et al (2001) Usefulness of plasma exchange plus continuous hemodiafiltration to reduce adverse effects associated with plasma exchange in patients with acute liver failure. Crit Care Med 29:1386–1392PubMedCrossRefGoogle Scholar
  32. 32.
    Sauer IM, Goetz M, Steffen I et al (2004) In vitro comparison of the molecular adsorbent recirculation system (MARS) and single-pass albumin dialysis (SPAD). Hepatology 39:1408–1414PubMedCrossRefGoogle Scholar
  33. 33.
    Seige M, Kreymann B, Jeschke B et al (1999) Long-term treatment of patients with acute exacerbation of chronic liver failure by albumin dialysis. Transplant Proc 31:1371–1375PubMedCrossRefGoogle Scholar
  34. 34.
    Sen S, Felldin M, Steiner C et al (2002) Albumin dialysis and Molecular Adsorbents Recirculating System (MARS) for acute Wilson’s disease. Liver Transpl 8:962–967PubMedCrossRefGoogle Scholar
  35. 35.
    Singer AL, Olthoff KM, Kim H et al (2001) Role of plasmapheresis in the management of acute hepatic failure in children. Ann Surg 234:418–424PubMedCrossRefGoogle Scholar
  36. 36.
    Stange J, Mitzner S, Ramlow W et al (1993) A new procedure for the removal of protein bound drugs and toxins. Asaio J 39:M621–M625PubMedCrossRefGoogle Scholar
  37. 37.
    Stange J, Ramlow W, Mitzner S et al (1993) Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. Artif Organs 17:809–813PubMedCrossRefGoogle Scholar
  38. 38.
    Tan HK, Yang WS, Chow P et al (2007) Anticoagulation minimization is safe and effective in albumin liver dialysis using the molecular adsorbent recirculating system. Artif Organs 31:193–199PubMedCrossRefGoogle Scholar
  39. 39.
    Wiesner R, Edwards E, Freeman R et al (2003) Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124:91–96PubMedCrossRefGoogle Scholar

Copyright information

© Spinger 2009

Authors and Affiliations

  • A. Al-Chalabi
    • 1
  • B. Kreymann
    • 1
    • 2
  • J. Langgartner
    • 3
  • T. Brünnler
    • 3
  1. 1.Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der IsarTechnische Universität MünchenMünchenDeutschland
  2. 2.Hepa Wash GmbHGarchingDeutschland
  3. 3.Klinik und Poliklinik für Innere Medizin IUniversität RegensburgRegensburgDeutschland

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