Zusammenfassung
Medikamentös-toxische Leberschädigungen („drug-induced liver injury“ [DILI]) sind seltene, aber teils lebensbedrohliche Ereignisse. Abzugrenzen von der intrinsischen Leberschädigung, die vorhersagbar und reproduzierbar nach einer Überdosis Paracetamol auftritt, ist die idiosynkratische DILI – eine Leberentzündung, die meist mit einer Latenz von Wochen bis Monaten, dosisunabhängig und nicht vorhersagbar als Reaktion auf die Einnahme vieler verschiedener Präparate auftritt. Die Ursache dafür, dass bestimmte Medikamente bei einzelnen Personen einen Leberschaden hervorrufen, ist bisher nicht gänzlich geklärt. Allerdings ist mittlerweile bekannt, dass das Immunsystem eine zentrale Rolle spielt, was durch die Assoziation bestimmter Polymorphismen humaner Leukozytenantigene (HLA) mit DILI durch spezifische Medikamentenklassen unterstrichen wird. Aufgrund der immunologischen Vorgänge, die zur Leberschädigung führen, zeigen sich laborchemisch und histologisch viele Überschneidungen insbesondere zur Autoimmunhepatitis (AIH), was eine diagnostische Abgrenzung oft schwierig macht. Neben der konventionellen DILI gibt es weitere Phänotypen, die als autoimmunähnlich gewertet werden. So wurde erst kürzlich ein Konsensusreport zur Definition und Charakterisierung einer neuen DILI-Entität, der „drug-induced autoimmune-like hepatitis“ (DI-ALH), publiziert. Die DI-ALH zeigt große Überschneidungen zur idiopathischen AIH, spricht ebenfalls gut auf Kortikosteroide an, zeichnet sich aber durch ein meist fehlendes Rezidiv nach Absetzen der Immunsuppression aus. Ebenfalls zu den immunologischen Leberschädigungen werden die Reaktionen auf Checkpointinhibitoren und Impfungen gezählt, wobei sich histopathologisch ein anderes Schädigungsmuster mit Überwiegen zytotoxischer T‑Zellen zeigt.
Abstract
Drug-induced liver injury (DILI) is a rare yet potentially life-threatening disease. Besides intrinsic DILI, which is mainly caused by paracetamol overdosing and which is dose-dependent and predictable, there is idiosyncratic DILI—an unpredictable and dose-independent injury of the liver caused by certain medications that only occurs in a minority of patients taking this drug. The reason why some patients react with DILI towards a specific drug is still unknown. However, the immune system plays a central role, which is underlined by the association of certain human leukocyte antigen (HLA) polymorphisms and DILI caused by specific drug classes. Due to the immunological processes that lead to the liver injury in DILI, there are great overlaps regarding laboratory and histological parameters between DILI and autoimmune hepatitis (AIH). Differentiating DILI and AIH can therefore be challenging, especially at the time of presentation. In addition, there are other immunologically mediated DILI phenotypes, in particular the newly defined drug-induced autoimmune-like hepatitis (DI-ALH) and liver injuries caused by checkpoint inhibitors (CPI). DI-ALH is characterized by autoimmune features and good responses towards corticosteroids, with the difference that DI-ALH mostly does not relapse after discontinuation of corticosteroids. CPI-induced liver injury has become more frequent with the rising use of those drugs and is characterized by a distinct histopathological pattern with granulomatous hepatitis and infiltration dominated by cytotoxic T cells. Similarly, the recently recognized liver injury following vaccinations also shows an autoimmune phenotype; however, in contrast to AIH, cytotoxic T cells seem to dominate the inflammatory infiltrates in the liver.
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Weber, S. Arzneimittelinduzierte immunvermittelte Leberschädigung. Innere Medizin 65, 334–339 (2024). https://doi.org/10.1007/s00108-024-01669-4
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DOI: https://doi.org/10.1007/s00108-024-01669-4
Schlüsselwörter
- Autoimmunhepatitis
- Medikamentennebenwirkungen und unerwünschte Reaktionen
- Autoimmunität
- Immuncheckpointinhibitoren
- Impfungen