Extrakorporale Unterstützungsstrategien beim Leberversagen

Die theoretische Rationale für die Kombination aus Albumindialyse und einer klassischen Hämodialyse bei akutem (ALF) und akut-auf-chronischem Leberversagen (ACLF) ist gut verständlich. Dennoch konnte bisher nur für den therapeutischen Plasmaaustausch (TPE) ein Überlebensvorteil beim ALF nachgewiesen werden. Dieser Beitrag stellt das Prinzip der Albumindialyse und des TPE sowie die wichtigsten Studien zu diesen Verfahren bei ALF und ACLF dar.

Abstract

Combining albumin dialysis for the removal of hydrophobic substances with classical haemodialysis in the treatment of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) has a strong theoretical rational and clinical data showed a positive effect on laboratory and partly clinical characteristics of ALF and ACLF. However, neither the MARS nor the Prometheus System has so far been able to demonstrate a mortality benefit in ALF or ACLF patients. To date, only the use of therapeutic plasma exchange (TPE) has demonstrated significant removal of pathogen-associated (PAMPs), damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines. In addition, TPE also acts simultaneously by replacing protective but depleted mediators, thus improving multiple key pathophysiological principles of both ALF and ACLF. In ALF, both high-volume and standard-volume TPE showed a significant improvement in survival. The data on the use of TPE in ACLF is still sparse, with only two Chinese monocentric studies in patients with exclusively hepatitis B-associated ACLF suggesting potentially improved survival with TPE. The currently recruiting APACHE study will include patients with the modern EASL-CLIF definition of ACLF.

Kernaussagen

• Sowohl das ALF als auch das ACLF sind durch ein hepatisches und ein extrahepatisches Multiorganversagen charakterisiert.

• Pathophysiologisch zentral ist hier das Zusammenspiel von unkontrollierter Inflammation, Koagulationsstörung und endothelialer Dysfunktion.

• Albumindialyse entfernt sowohl wasserlösliche als auch proteingebundene Toxine beim Leberversagen.

• Der therapeutische Plasmaaustauch entfernt zudem DAMPs, PAMPs und proinflammatorische Zytokine und führt über den Ersatz mit Plasma gesunder Spender zum Ausgleich protektiver, aber verbrauchter Faktoren.

• Additive Albumindialyse konnte bisher keine Verbesserung des Überlebens bei Patienten mit ALF oder ACLF zeigen.

• Therapeutischer Plasmaaustausch verbessert das transplantationsfreie Überleben bei Patienten mit ALF. Bei Patienten mit ACLF ist eine große klinische Studie in der Rekrutierungsphase, um den Effekt von Plasmaaustausch zu untersuchen.

Schlüsselwörter

akutes Leberversagen - akut-chronisches Leberversagen - extrakorporale Therapie - Albumindialyse - therapeutischer Plasmaaustausch

Keywords

acute liver failure - acute-on-chronic failure - extracorporeal therapy - Albumin dialysis - therapeutic plasma exchange

Publication History

Article published online:
17 May 2024

• Literatur

• 1 Saliba F, Camus C, Durand F. et al. Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. Ann Intern Med 2013; 159: 522-531 DOI: 10.7326/0003-4819-159-8-201310150-00005. (PMID: 24126646)
• 2 MacDonald AJ, Subramanian RM, Olson JC. et al. Use of the molecular adsorbent recirculating system in acute liver failure: results of a multicenter propensity score-matched study. Crit Care Med 2022; 50: 286-295 DOI: 10.1097/CCM.0000000000005194. (PMID: 34259656)
• 3 Larsen FS, Schmidt LE, Bernsmeier C. et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 2016; 64: 69-78 DOI: 10.1016/j.jhep.2015.08.018. (PMID: 26325537)
• 4 Maiwall R, Bajpai M, Singh A. et al. Standard-volume plasma exchange improves outcomes in patients with acute liver failure: a randomized controlled trial. Clin Gastroenterol Hepatol 2022; 20: e831-e854 DOI: 10.1016/j.cgh.2021.01.036. (PMID: 33524593)
• 5 Bañares R, Nevens F, Larsen FS. et al. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: the RELIEF trial. Hepatology 2013; 57: 1153-1162 DOI: 10.1002/hep.26185. (PMID: 23213075)
• 6 Kribben A, Gerken G, Haag S. et al. Effects of fractionated plasma separation and adsorption on survival in patients with acute-on-chronic liver failure. Gastroenterology 2012; 142: 782-789.e3 DOI: 10.1053/j.gastro.2011.12.056. (PMID: 22248661)
• 7 Yu JW, Sun LJ, Zhao YH. et al. Prediction value of model for end-stage liver disease scoring system on prognosis in patients with acute-on-chronic hepatitis B liver failure after plasma exchange and lamivudine treatment. J Gastroenterol Hepatol 2008; 23: 1242-1249 DOI: 10.1111/j.1440-1746.2008.05484.x. (PMID: 18637053)
• 8 Qin G, Shao JG, Wang B. et al. Artificial liver support system improves short- and long-term outcomes of patients with HBV-associated acute-on-chronic liver failure: a single-center experience. Medicine (Baltimore) 2014; 93: e338 DOI: 10.1097/MD.0000000000000338. (PMID: 25526495)
• 9 Stadlbauer V, Krisper P, Aigner R. et al. Effect of extracorporeal liver support by MARS and Prometheus on serum cytokines in acute-on-chronic liver failure. Crit Care 2006; 10: R169 DOI: 10.1186/cc5119. (PMID: 17156425)
• 10 Falkenhagen D, Strobl W, Vogt G. et al. Fractionated plasma separation and adsorption system: a novel system for blood purification to remove albumin bound substances. Artif Organs 1999; 23: 81-86 DOI: 10.1046/j.1525-1594.1999.06292.x. (PMID: 9950184)
• 11 Drexler K, Baustian C, Richter G. et al. Albumin dialysis molecular adsorbents recirculating system: impact of dialysate albumin concentration on detoxification efficacy. Ther Apher Dial 2009; 13: 393-398 DOI: 10.1111/j.1744-9987.2009.00757.x. (PMID: 19788455)
• 12 Stahl K, Wendel-Garcia PD, Bode C. et al. Unraveling the secret of re-balancing homeostasis in sepsis: a critical view on extracorporeal blood purification modalities. Intensive Care Med 2022; 48: 130-132 DOI: 10.1007/s00134-021-06560-6. (PMID: 34713314)
• 13 Stahl K, Schmidt JJ, Seeliger B. et al. Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock. Crit Care 2020; 24: 71 DOI: 10.1186/s13054-020-2799-5. (PMID: 32122366)
• 14 Wendon J, Cordoba J, Dhawan A. et al. EASL Clinical Practical Guidelines on the management of acute (fulminant) liver failure. J Hepatol 2017; 66: 1047-1081 DOI: 10.1016/j.jhep.2016.12.003. (PMID: 28417882)
• 15 Saliba F, Bañares R, Larsen FS. et al. Artificial liver support in patients with liver failure: a modified DELPHI consensus of international experts. Intensive Care Med 2022; 48: 1352-1367 DOI: 10.1007/s00134-022-06802-1. (PMID: 36066598)
• 16 Stahl K, Hadem J, Schneider A. et al. Therapeutic plasma exchange in acute liver failure. J Clin Apher 2019; 34: 589-597 DOI: 10.1002/jca.21737. (PMID: 31348553)
• 17 Tan EX, Wang MX, Pang J. et al. Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review. World J Gastroenterol 2020; 26: 219-245 DOI: 10.3748/wjg.v26.i2.219. (PMID: 31988586)
• 18 Beran A, Mohamed MFH, Shaear M. et al. Plasma exchange for acute and acute-on-chronic liver failure: A systematic review and meta-analysis. Liver Transpl 2024; 30: 127-141 DOI: 10.1097/LVT.0000000000000231. (PMID: 37530812)
• 19 Bañares R, Ibáñez-Samaniego L, Torner JM. et al. Meta-analysis of individual patient data of albumin dialysis in acute-on-chronic liver failure: focus on treatment intensity. Therap Adv Gastroenterol 2019; 12: 1756284819879565 DOI: 10.1177/1756284819879565. (PMID: 31632458)
• 20 Moreau R, Jalan R, Gines P. et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology 2013; 144: 1426-1437.e1–9 DOI: 10.1053/j.gastro.2013.02.042. (PMID: 23474284)
• 21 Agarwal B, Cañizares RB, Saliba F. et al. Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure. J Hepatol 2023; 79: 79-92 DOI: 10.1016/j.jhep.2023.03.013. (PMID: 37268222)