Etablierte Therapien und neue therapeutische Ansätze bei der alkoholischen Leberkrankung

Zusammenfassung

Chronischer Alkoholmissbrauch ist die Ursache von über 200 Erkrankungen und/oder Symptomen, wobei der alkoholischen Lebererkrankung (ALE) besondere Bedeutung zukommt, da sie häufig auftritt und oft lebensbedrohlich ist. In Europa sind der Alkoholkonsum sowie die ALE im Vergleich zum Rest der Welt gestiegen. Schätzungen zufolge sterben in Europa ca. 500 000 Menschen jährlich an einer ALE. Zu den alkoholischen Lebererkrankungen zählen die alkoholische Fettleber (AFL), die alkoholische Steatohepatitis (ASH), die alkoholische Zirrhose (ACI) sowie das hepatozelluläre Karzinom (HCC). Die alkoholische Hepatitis (AH) ist ein klinisches Syndrom mit Ikterus, Leberversagen und einer hohen Sterblichkeitsrate. Der Verlauf der ALE ist variabel und hängt u. a. von der Genetik, dem Geschlecht, der gleichzeitigen Präsenz anderer Lebererkrankungen sowie der gleichzeitigen Exposition gegenüber toxischen Substanzen und Medikamenten ab. Die Behandlung der ALE beschränkt sich hauptsächlich auf Alkoholkarenz, die beim Alkoholiker schwierig zu realisieren ist. Die Ergebnisse der Therapie werden durch eine kognitive Psychotherapie verbunden mit Anti-craving-Medikamenten verbessert. Die Behandlung der AH mit ihrer schlechten Prognose ist begrenzt. Obwohl eine ganze Reihe therapeutischer Ansätze bei der AH versucht wurden, besteht die gegenwärtige Therapie aus einer intensivmedizinischen Überwachung in Verbindung mit der Gabe von Steroiden, einer Hyperalimentation und möglicherweise der Gabe von N-Acetylcystein. Zurzeit wird darüber diskutiert, ob eine Lebertransplantation bei AH sinnvoll ist. Neuere therapeutische Ansätze konzentrieren sich auf pathophysiologisch identifizierte Zielfaktoren bei der ALE. Diese umfassen die Ausschaltung von Endotoxinen, bestimmte Zytokine und Chemokine sowie die Hemmung von oxidativem Stress. Auch Anti-craving-Substanzen wie Nalmefen können die Leberfunktion verbessern, da durch ihre Zufuhr weniger Alkohol konsumiert wird. Darüber hinaus wurde Betain zur Stimulierung des Methyltransfers und Ansätze zur Hemmung der Apoptose untersucht. Die Stimulation der Leberregeneration mittels Granulozytenkolonien-stimulierendem Faktor sowie Mesenchymzellen- und Knochenmarktransplantation zeigen vielversprechende Ergebnisse. Dennoch sind neue Therapieformen dringend erforderlich, insbesondere bei der ASH mit ihrer hohen Mortalität.

Abstract

Chronical alcohol abuse causes more than 200 diseases and/or symptoms and among these alcoholic liver disease (ALD) is of special importance since it occurs frequently and may be life-threatening. In Europe alcohol consumption as well as ALD increased as compared to the rest of the world. It has been estimated that in Europe approximately 500 000 people die every year due to ALD. ALD consists of alcoholic fatty liver, alcoholic steatohepatitis (ASH), alcoholic cirrhosis and hepatocellar cancer (HCC ). Alcohol hepatitis (AH) is a clinical feature with jaundice and liver failure and a high mortality. The course of ALD is variable and depends among others, on genetics, gender, the presence of other liver diseases as well as exposure towards toxic substances and drugs. The treatment of ALD mainly consists of alcohol abstinence which may be difficult to achieve in the alcoholic. The results of the therapy improve by cognitive psychotherapy as well as antigraving medication. The treatment of AH with poor prognosis is limited. Although a number of therapeutic approaches in AH have been tried, the present therapy consists of intensive care in association with the administration of steroids, hyperalimentation and possibly the administration of N-acetylcystein. Presently it is discussed whether liver transplantation is an option for these patients. New therapeutic approaches focuses on pathopyhsiologically identified targets in ALD. This includes elimination of endotoxines, cytokines, and chemokines as well as an inhibition oxidative stress. Antigraving substances, such as Nalmafen also may improve liver function since their administration degreases alcohol consumption. In addition, betain to stimulate methyltransfer as well the inhibition of apoptosis have been investigated. Stimulation of liver regeneration by granulozytecolony stimulating factor as well as mesenchymalcell and bone marrow transplantation have shown some positive results. Nevertheless new therapeutic strategies are urgently needed. Especially in AH with its high mortality.

Schlüsselwörter

alkoholische Leberkrankung - alkoholische Hepatitis - Therapie der alkoholischen Lebererkrankung

Key words

alcoholic liver disease - alcoholic hepatitis - therapy of alcoholic liver disease

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