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Der Klinikarzt 2012; 41(06/07): 310-314
DOI: 10.1055/s-0032-1326978
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© Georg Thieme Verlag Stuttgart · New York

Alkoholische Leberzirrhose – Die Sicht des Toxikologen

Alcoholic liver cirrhosis – Toxicologically Aspects
Thomas Zilker
1   Toxikologische Abteilung, II. Med. Klinik der Technischen Universität München
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Publication Date:
28 August 2012 (online)

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Man kennt bereits eine Vielfalt von pathogenen Mechanismen, die die Entwicklung einer Leberzirrhose unter Äthanoleinfluss begünstigen. Äthanol selbst ist wenig lebertoxisch. Problematisch ist der Acetaldehyd, der bei der Oxidation von Äthanol zusammen mit Sauerstoffradikalen, die über das „Mikrosomal Induzierte Ethanol Oxidierende System” (MEOS) generiert werden, entsteht. Dadurch verlagert sich das Redoxpotenzial und erzeugt einen „oxidativen Stress“. Ein mangelnder Fettsäureabbau führt zur Fetteinlagerung in die Leberzellen. Chemokinine wie Interleukin 8, Leukotrien B4, TNF-Alpha und TRAIL führen zu entzündlichen Reaktionen mit Aktivierung von Neutrophilen und damit zur Fettleberhepatitis. Bei chronischer Aktivierung dieser Systeme kommt es zur Schädigung der Extrazellulären Matrix der Leber (ECM) mit interstitieller Kollagenbildung. Verantwortlich ist eine parakrine Aktivierung der Ito-Zellen aus den Kupffer'schen Sternzellen, die zu Kollagenfasern proliferieren. Ob man Patienten mit einer alkoholischen Leberzirrhose einer Lebertransplantation zuführen soll, wird heftig diskutiert. Wenn man die Alkoholabhängigkeit als Krankheit begreift, so ist dies zu bejahen. Wegen dem Mangel an Spendern ist man zur Selektion gezwungen. Für eine günstige Prognose bezüglich einer Alkoholabstinenz sprechen eine kürzere Dauer der Abhängigkeit, ein geringerer täglicher Alkoholkonsum, eine gute soziale Einbindung und keine psychiatrische Komorbidität. Der Erfolg der Lebertransplantation ist bei der äthylischen Leberzirrhose günstig. Mäßiger, nicht jedoch massiver Äthanolkonsum beeinflusst das Transplantatüberleben kaum. Viele Studien haben gezeigt, dass die Rückfallquoten bei circa 25 % liegen.

A lot is known about the pathogenesis of alcoholic liver cirrhosis. Ethanol itself does little harm to the liver. Acetaldehyd generated by oxidation of ethanol together with Reactive Oxygen Species (ROS) are causing the damage. Through the Microsomal Ethanol-Oxidizing System (MEOS) the redox potential is creating an oxidative stress. A deficiency of fatty-acid oxidation leads to fat accumulation inside the hepatocytes. Chemokinines like Interleucin 8, Leukotrien B4, TNF-Alpha and TRAIL lead to an inflammatory reaction with activation of neutrophiles and to steatohepatitis. Following a permanent activation of these systems the extracellular matrix (ECM) of the liver is damaged. Responsible is a parakrine activation of the Ito cells from Kupffer'sche stellate cells which triggers the production of collagen fibers.

Whether alcoholics should undergo liver transplantation is a matter of dispute. If alcohol dependency is a disease one should not hesitate to perform liver transplantation in these patients. Nevertheless one is forced to do selection as there is a lack of organs. A favorable prognosis for abstinence after LTx can be found in patients with a shorter duration of addiction, a fewer daily intake, a better social binding and no psychiatric co-morbidity. Most LTx in alcoholic liver cirrhosis are successful. Moderate but no excessive alcohol consumption does not influence graft survival. Many studies have shown, that the relapse rate is on average 25 % after LTx.

Key words

alcoholic liver cirrhosis - alcoholic dependancy - liver transplantation –relapse
 

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