Medikamentöse Schädigung der Leber mit autoimmunem Phänotyp durch TNF-Blockade – Fallvorstellung und Review der Literatur^[1]

Zusammenfassung

Die Zulassung von Medikamenten, die die biologische Wirkung von Tumor-Nekrose-Faktor alpha (TNF-α) blockieren, hat die Behandlungsmöglichkeiten von Patienten mit einer Reihe von autoimmun-vermittelten Erkrankungen stark verbessert. Als häufige Nebenwirkung kommt es zu einer gesteigerten Anfälligkeit gegenüber Infekten. Selten treten auch hepatische Nebenwirkungen unter TNF-Blockade auf. Diese reichen von einer moderaten Leberwert- und Bilirubinerhöhung über die Reaktivierung von chronischen Viruserkrankungen, können aber auch zum akuten Leberversagen führen. In einem Teil der Fälle wurde ein autoimmunes Schädigungsmuster mit dem Auftreten von Autoantikörpern und entsprechenden typischen histopathologischen Veränderungen beschrieben. Wir berichten über 3 Patienten mit unterschiedlichem Verlauf einer durch Anti-TNF-Therapie induzierten Hepatopathie, die aufgrund einer Psoriasis behandelt wurden. In der Literatur existieren nur wenige gut charakterisierte Fälle einer medikamenteninduzierten Leberschädigung (drug-induced liver injury; DILI) mit Autoimmunphänomenen und vor dem Hintergrund des steigenden Einsatzes dieser Substanzklassen stellt dies eine ernst zu nehmende Nebenwirkung dar. Da die zugrunde liegenden Pathomechanismen nicht hinreichend verstanden sind, helfen die geschilderten Fälle, das Verständnis dieser Phänomene zu verbessern.

Abstract

Therapeutic agents to inhibit tumour necrosis factor alpha (TNF-α) have dramatically improved the treatment options for patients with autoimmune diseases. Common side effects include an increased susceptibility towards infection. Hepatic side effects are less frequently observed. Elevated liver function tests, hyperbilirubinaemia reactivation of chronic viral hepatitis or even acute liver failure have been described. Some cases have exhibited an autoimmune phenotype with the emergence of autoantibodies and characteristic histological lesions. We report on three patients who received anti-TNF therapy for psoriasis and presented with elevated liver function tests in the further course. Histological and serum analysis revealed an autoimmune phenotype of liver injury. In light of the growing use of anti-TNF therapies, drug-induced liver injury (DILI) with an autoimmune phenotype is an important side effect. Since the pathophysiological mechanisms related to the autoimmune phenotype of liver injury during TNF-inhibition are not well understood, the cases detailed herein should help treating physicians to improve their understanding of the situation.

Schlüsselwörter

medikamentös-toxische Leberschädigung - medikamenteninduzierte Autoimmunhepatitis (AIH) - Anti-TNF-Therapie - Leber

Key words

drug-induced liver injury (DILI) - drug-induced autoimmune hepatitis (DIH) - anti-TNF therapy - liver

¹ Teile der Fallvorstellungen sind als Abstract im Rahmen der Jahrestagung der Gastroenterologischen Arbeitsgemeinschaft Rheinland-Pfalz/Saarland (GARPS) 2013 vorgestellt worden.

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