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LKM免疫荧光与药物性肝损伤相关,尤其是在服用安乃近之后。

LKM Immunofluorescence Is Associated with DILI, Especially after Metamizole Intake.

作者信息

Bock Kilian, Engel Bastian, Jaeckel Elmar, Wedemeyer Heiner, Mederacke Ingmar, Mederacke Young-Seon

机构信息

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover, Germany,

Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover, Germany.

出版信息

Dig Dis. 2025 Mar 28:1-11. doi: 10.1159/000545507.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

引言

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。

方法

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e638/12060832/c34541d0d8b1/ddi-2025-0000-0000-545507_F01.jpg

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