CMV-assoziiertes Leberversagen bei einer Patientin mit systemischem Lupus erythematodes unter Immunsuppression mit Tocilizumab

Zusammenfassung

Eine 41-jährige Patientin wurde mit fieberhaftem Ikterus unter dem Bild eines akuten Leberversagens aufgenommen. Der Quick-Wert lag bei 21 %, das Bilirubin bei 258 µmol/l und es bestand eine hepatische Enzephalopathie. GOT und AP lagen max. bei 612 und 215 U/l. Trotz einer starken Linksverschiebung erreichte das CRP nur ein Maximum von 15 mg/l. Wegen eines atypisch verlaufenden systemischen Lupus erythematodes hatte sie bis 12 Tage vor Aufnahme eine Therapie mit Azathioprin, Prednisolon und Tocilizumab erhalten. Die Abklärung erbrachte eine CMV-Hepatitis und einen nekrotisierenden Leberschaden, der als medikamentös-toxisch gewertet wurde. Zum Zeitpunkt der Leberbiopsie, an Tag 3 nach Aufnahme, zeigte sich anhand der Ki-67 Färbung eine ausgeprägte regeneratorische Aktivität in der Leber. Unter einer Therapie mit Valganciclovir, einer Antibiose und einer erhöhten Steroiddosis kam es zur raschen Besserung des Leberversagens. Der Fall unterscheidet sich von den wenigen beschriebenen Fällen einer schweren akuten Leberschädigung unter Tocilizumab. Offensichtlich kam es im Zusammenhang mit der kombinierten Immunsuppression (Steroid, Azathioprin und Tocilizumab) durch die Kombination der CMV-Hepatitis und des medikamentös-toxischen Leberschadens sowie einer möglicherweise passager eingeschränkten Regeneration zum akuten Leberversagen. Andererseits kam es trotz IL6-Blockade durch Tocilizumab zu einer raschen, bioptisch gesicherten Regeneration.

Abstract

A 41-year-old female patient was admitted because of febrile jaundice and acute liver failure. The quick and the bilirubin were 21 % and 258 µmol/l, and there was hepatic encephalopathy I°. AST and AP had a maximum of 612 and 215 U/l. Despite a strong left shift in the differential, the CRP had a maximum of 15 mg/l. Because of an atypically presenting systemic lupus erythematosus, she had been treated with Azathioprine, steroids and Tocilizumab until 12 days before admission. The diagnostic workup revealed CMV hepatitis and necrotizing hepatopathy, which was interpreted as toxic hepatitis. At the time of liver biopsy, on day 3 after admission, staining for Ki-67 indicated strong regenerative activity in the liver. Treatment with Valgancyclovir, antibiotics and steroids led to early recovery from liver failure. The case differs from the few described cases of severe acute liver injury related to Tocilizumab. Apparently, the combined immunosuppression (steroid, Azathioprine and Tocilizumab) led to acute liver failure secondary to CMV hepatitis and acute toxic hepatitis, which may have been aggravated by transiently impaired liver regeneration. On the other hand, stimulated liver regeneration was proven by histology despite previous IL6 blockage by Tocilizumab.

Schlüsselwörter

akutes Leberversagen - Tocilizumab - CMV-Hepatitis - medikamentös-toxischer Leberschaden - Leberregeneration

Key words

acute liver failure - Tocilizumab - CMV hepatitis - toxic hepatitis - liver regeneration

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