Bock Kilian, Engel Bastian, Jaeckel Elmar, Wedemeyer Heiner, Mederacke Ingmar, Mederacke Young-Seon
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover, Germany,
Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover, Germany.
Dig Dis. 2025 Mar 28:1-11. doi: 10.1159/000545507.
Drug-induced liver injury (DILI) is a rare but potentially serious clinical condition. One phenotype of DILI is termed drug-induced autoimmune like hepatitis (DI-ALH) that presents with laboratory and histological features indistinguishable from autoimmune hepatitis. Liver kidney microsomal antibodies (LKM-antibodies) are common in the diagnosis of AIH but were also described to be associated with halothane-induced DILI. Also, the antigens of anti-LKM-1 and anti-LKM-2 belong to the cytochrome P450 enzyme family that is involved in the metabolism of various drugs. Therefore, we aimed to study the impact of LKM-antibodies in the diagnostic work-up of suspected DILI in a large cohort of patients with liver injury in a tertiary care centre.
We screened a large single centre hospital database and retrospectively identified 63,300 cases with liver injury as defined: AST or ALT >3 upper limit of normal (ULN) or AP or TBI >2 ULN. Of those, 82 cases with LKM immunofluorescence positivity (titre ≥1: 160) were identified, of which 64 patients fulfilled the inclusion criteria for this study.
Positive LKM immunofluorescence was associated with drug-induced autoimmune-like hepatitis (DI-ALH). Metamizole association was identified in half of the patients (n = 33, 52%). Eight patients with metamizole associated DI-ALHs required liver transplantation and 1 patient died.
DI-ALH, especially after metamizole administration, can be a reason for a positivity in LKM immunofluorescence tests. Metamizole DI-ALH has a high liver-related mortality.
药物性肝损伤（DILI）是一种罕见但可能严重的临床病症。DILI的一种表型被称为药物性自身免疫性肝炎样（DI-ALH），其实验室和组织学特征与自身免疫性肝炎难以区分。肝肾微粒体抗体（LKM抗体）在自身免疫性肝炎（AIH）的诊断中很常见，但也被描述与氟烷诱导的DILI有关。此外，抗LKM-1和抗LKM-2的抗原属于参与各种药物代谢的细胞色素P450酶家族。因此，我们旨在研究在一家三级医疗中心的一大群肝损伤患者中，LKM抗体在疑似DILI诊断检查中的影响。
我们筛查了一个大型单中心医院数据库，并回顾性确定了63300例肝损伤病例，定义为：AST或ALT>正常上限（ULN）的3倍，或AP或TBI>2倍ULN。其中，82例LKM免疫荧光阳性（滴度≥1:160）被确定，其中64例患者符合本研究的纳入标准。
LKM免疫荧光阳性与药物性自身免疫性肝炎样（DI-ALH）相关。一半患者（n = 33，52%）确定与安乃近有关。8例与安乃近相关的DI-ALH患者需要肝移植，1例死亡。
DI-ALH，尤其是在服用安乃近后，可能是LKM免疫荧光试验阳性的原因。安乃近所致DI-ALH具有较高的肝脏相关死亡率。
