Extrakorporale Leberunterstützungsverfahren beim Leberversagen

Zusammenfassung

Als extrakorporale Leberunterstützungstherapie werden die zellfreien – artifiziellen Verfahren (artificial liver support, ALS) von den zellbasierten – bioartifiziellen Verfahren (bioartificial liver support, BLS) unterschieden. Die artifiziellen Verfahren, verbessern durch die gleichzeitige Entfernung von proteingebundenen und wasserlöslichen Substanzen biochemische Parameter des Leberversagens. Hierbei gehört die MARS-Therapie zu dem am besten untersuchten Verfahren, wobei ein Effekt bzgl. der Symptomkontrolle der hepatischen Enzephalopathie (HE), dem hepatorenalen Syndrom (HRS) oder der Hyperbilirubinämie nachgewiesen werden konnte. Ein genereller Überlebensvorteil jedweder Leberdialyse beim Leberversagen lässt sich jedoch nicht bzw. nur in Metaanalysen oder für Subgruppen zeigen. Es existieren keine prospektiv randomisierten Studien zur Therapie des Leberversagens durch Intoxikationen. Mehrere Fallserien berichten jedoch von positiven Therapieeffekten unter Verwendung des MARS-Systems, insbesondere bei Knollenblätterpilzvergiftungen oder Paracetamolintoxikationen. Beim akuten Leberversagen (ALF) konnten Studien unter Verwendung der BLS keinen Überlebensvorteil zeigen. Unter Verwendung von ALS-Systemen konnte in Patientensubgruppen nach mehreren konsekutiven MARS-Therapien ein positiver Effekt auf die Mortalität erreicht werden. Die bislang einzige prospektiv, randomisierte Studie mit signifikantem Überlebensvorteil verwendete großvolumige Plasmapherese als Therapieverfahren. Offenbar spielen hier immunmodulatorische und hämodynamische Effekte der Therapie eine entscheidende Rolle. Bei Patienten mit akut-auf-chronischem Leberversagen (acute on chronic liver failure, ACLF) und Hyperbilirubinämie ohne weiteres Organversagen (singuläre hepatische Dysfunktion) hat ein BLS-System prognostisch günstige Effekte gezeigt. Sobald jedoch auch andere extrahepatische Organsysteme betroffen sind und ein fortschreitender Übergang ins Multiorganversagen vorliegt, konnte mit dem MARS- bzw. Prometheus-Systems ein Überlebensvorteil erreicht werden. Entscheidend für einen Therapieerfolg ist die genaue Indikationsstellung des jeweiligen Leberdialyseverfahrens bei diesem sehr heterogenen Krankheitsbild. Zukünftige Studien sind nötig, um genauere Patientenselektionskriterien bzgl. des jeweiligen Leberunterstützungsverfahrens zu definieren.

Abstract

Extracorporeal liver support can be classified into cell-free, artificial methods (artificial liver support, ALS) and cell-based bioartificial methods (bioartificial liver support, BLS). ALS improves biochemical parameters of liver failure by the simultaneous removal of protein-bound and water-soluble substances. Here, the MARS therapy belongs to the most studied methods with a proved beneficial effect on hepatic encephalopathy (HE), hepatorenal syndrome (HRS) or hyperbilirubinemia. However, a general survival advantage of any liver support for liver failure has not been shown yet and is restricted to meta-analyses or patient subgroups. There are no prospective randomized studies on the treatment of liver failure by intoxication. However, several case series report positive treatment effects using the MARS system, particularly in mushroom poisoning or acetaminophen intoxication. In acute liver failure (ALF) studies, the usage of BLS showed no survival advantage. Using ALS systems, a positive effect on mortality could be demonstrated in patient subgroups after several consecutive MARS therapies. The first randomized controlled trial demonstrating a survival benefit used large-volume plasmapheresis. Apparently, immunomodulatory and hemodynamic effects of the treatment play a crucial role in this context. In patients with acute-on-chronic liver failure (ACLF) accompanied by hyperbilirubinemia without any further organ failure (singular hepatic dysfunction), prognostic favorable effects by using a BLS system have been shown. However, once other extrahepatic organ systems are affected, indicating a progressive transition to multi-organ failure, a survival advantage could be achieved with the MARS and Prometheus system. Decisive for a successful therapy is the exact indication of the respective liver dialysis procedure for this very heterogeneous disease. Future studies are needed to define more accurate patient selection criteria for each liver support.

Schlüsselwörter

akutes Leberversagen - Akutes-auf-chronisches Leberversagen - extrakorporale Leberunterstützungsverfahren

Key words

acute liver failure - acute-on-chronic liver failure - extracorporeal liver support

^* These authors contributed equally to this work.

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