Alkoholische Lebererkrankung

Zusammenfassung

Die alkoholische Lebererkankung ist die häufigste Organmanifestation bei Alkoholkrankheit und es sterben jährlich mehr Menschen an alkoholischer Lebererkrankung als durch Verkehrsunfälle. Alkohol schädigt durch die Toxizität von Azetaldehyd, seinem ersten Metaboliten, und durch Interaktion im Stoffwechsel zahlreicher Makro- und Mikronährstoffe die Leber. In der Behandlung sind die psychotherapeutische Suchttherapie, die Ernährungstherapie und die internistisch-hepatologische Behandlung von Komplikationen der Lebererkankung etabliert.

Da diese Verfahren für viele Patienten nicht ausreichend wirksam sind, werden auch medikamentöse Therapien alkoholbedingter Leberschäden untersucht. Unter den zahlreichen getesteten Substanzen haben sich viele als unwirksam oder toxisch erwiesen, einige sind jedoch viel versprechende Präparate. Hierzu gehören S-Adenosyl-L-Methionin (SAMe), Pentoxifyllin, Metadoxin, Polyenylphosphatidylcholin (PPC) und Inhibitoren des Cytochrom-P4502E1-Isoenzyms. Für schwerkranke Patienten mit Alkoholhepatitis werden gegenwärtig Substanzen mit Anti-Tumornekrose-Faktor-Wirkung getestet. Der therapeutische Nutzen von Glukokortikoiden ist kritisch zu bewerten und der Einsatz sollte sich auf ausgewählte Patienten beschränken. Anabole Steroide haben langfristig mehr Risiken als günstige Wirkungen. Inwieweit Silymarin sich bei Patienten, die noch keine Leberzirrhose aufweisen, wirksam ist, muss in Studien geklärt werden, die Wirksamkeit bei alkoholischer Leberzirrhose ist bisher nicht überzeugend gezeigt worden.

Abstract

Alcoholic liver disease is the most frequent organ damage encountered in chronic alcoholics and the annual death rate attributed to alcohol-induced end-stage liver disease exceeds that of car accidents. Alcoholic liver damage occurs mainly due to the toxicity of its first metabolite acetaldehyde, and due to interactions with numerous macro- and micronutrients. Established treatment options comprise psychotherapy aiming to achieve abstinence, nutritional therapy, management of hepatological complications, and liver transplantation in selected individuals.

Since these therapeutic approaches are unsuccessful in many patients, pharmacological therapies of alcoholic liver disease are being investigated. Many drugs failed to be beneficial or have even shown toxicity. However, some agents are promising, such as S-adenosyl-L-methionine (SAMe), pentoxifylline, metadoxin, polyenylphosphatidylcholine or inhibitors of the cytochrome P450 2E1 isoenzyme. In severely ill patients with alcoholic hepatitis, drugs with anti-tumor necrosis factor α activity are currently investigated in clinical trials. If and how far corticosteroids are beneficial remains controversial and their use should be restricted to selected patients. Anabolic steroids used to enhance the nutritional status may lead to serious side effects while having a marginal benefit. Silymarin has not been proven efficacious in alcoholic cirrhosis and clinical trials are ongoing which aim to elucidate its therapeutic value in less advanced stages of liver disease.

Schlüsselwörter

Alkoholkrankheit - Anti-TNF-α - Cytochrom P450 2E1 - Colchizin - Ernährungstherapie - Lebertransplantation - Leberzirrhose - Metadoxin - Pentoxifyllin - Polyenylphosphatidylcholin - S-Adenosyl-L-Methionin - Silymarin

Key words

Alcoholic liver disease - anti-TNF-α - cytochrome P450 2E1 - colchicine - nutritional therapy - liver transplantation - liver cirrhosis - metadoxin - pentoxifylline - polyenylphosphatidylcholine - s-adenosyl-l-methionine - silymarin

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