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Diagnostik und Behandlung des akuten Leberversagens

Wissenschaftliche Entwicklungen

Diagnosis and therapies for acute liver failure

Scientific developments

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Zusammenfassung

Hintergrund

Etwa 200 Patienten erkranken jedes Jahr in Deutschland an einem akuten Leberversagen (ALV). Aufgrund des seltenen Auftretens und der Schwere des Erkrankungsverlaufs stehen allerdings nur wenige evidenzbasierte Therapien zur Verfügung.

Fragestellung

Diese Übersichtsarbeit diskutiert die wichtigsten Entwicklungen in der Diagnostik und Therapie des ALV und gibt einen Ausblick auf ihre zukünftige klinische Relevanz.

Ergebnisse

Die etablierten Enzymparameter reflektieren in Kombination mit den die Synthese- bzw. Entgiftungsfunktion beschreibenden Markern nur unzureichend die Schwere und den Verlauf des ALV. Zukünftig könnte die Messung von ins Blut freigesetzten microRNAs und von Zytokeratin-18-Spaltprodukten das Repertoire der Diagnostik und Verlaufskontrolle verbessern. Zuletzt haben sich nur wenige neue medikamentöse Behandlungsansätze abgezeichnet, doch es wurde viel in die Evaluation artifizieller Leberunterstützungssysteme investiert. Aufgrund des günstigen Sicherheitsprofils werden die zellfreien Detoxifizierungssysteme heute punktuell in der Behandlung von Patienten mit fortgeschrittenen Lebererkrankungen eingesetzt, auch wenn größere Studien bisher keinen Überlebensvorteil nachweisen konnten. Extrakorporale Unterstützungssysteme sowie Zelltransplantationsverfahren sind durch die Verfügbarkeit metabolisch aktiver Spenderhepatozyten limitiert, weshalb der Differenzierung von Leberzellen aus geeigneten Stammzellen eine hohe Bedeutung beigemessen wird.

Schlussfolgerung

Die stammzellbiologische Forschung und das Tissue Engineering zeigen aktuell in ersten tierexperimentellen Studien Möglichkeiten auf, wie stammzellbasierte artifizielle Leberzellsysteme zur Behandlung des ALV eingesetzt werden können.

Abstract

Background

In Germany about 200 patients suffer from acute liver failure each year. Due to its rare occurrence and the severity of the disease course only few evidence-based therapeutic strategies are available.

Objectives

This review aims to discuss the most important developments for the diagnosis and therapy of acute liver failure and provides an outlook of their future clinical relevance.

Results

The established enzyme parameters combined with synthesis- and detoxification-related markers insufficiently predict the severity and disease course of acute liver failure. In future, levels of released microRNAs or cleaved cytokeratin 18 fragments may improve the diagnostic repertoire. Currently, only few drug-based therapeutic approaches are available, but much effort has been invested in artificial liver support devices. Based on their favorable risk assessment cell-free detoxification systems are applied sporadically during the treatment of patients with advanced liver diseases, even if to date larger studies have failed to prove a significant survival benefit. Extracorporeal liver assist devices and cell transplantation approaches rely on the availability of metabolically active donor hepatocytes and, thus, the generation of liver cells from appropriate stem cells is gaining interest.

Conclusion

Current research in stem cell biology and tissue engineering suggest in initial animal studies the feasibility of stem cell-based artificial liver support systems for future treatment of acute liver failure.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M. Ott, T. Cantz, A. Schneider und M.P. Manns geben an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren. Unser Beitrag ist ein Übersichtsartikel und beschreibt keine eigenen Originaldaten, denen Studien zugrunde liegen würden. Allerdings werden publizierte klinische Studien benannt und diskutiert.

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Authors and Affiliations

  1. Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Zentrum Innere Medizin, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    M. Ott, T. Cantz, A. Schneider &  M.P. Manns

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  1. M. Ott
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  2. T. Cantz
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Correspondence to M.P. Manns.

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Ott, M., Cantz, T., Schneider, A. et al. Diagnostik und Behandlung des akuten Leberversagens. Internist 55, 1288–1295 (2014). https://doi.org/10.1007/s00108-014-3507-9

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