Drug-Induced Liver Injury Caused by Metamizole: Identification of a Characteristic Injury Pattern

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-02-06 DOI:10.1111/liv.70012

Sabine Weber, Franziska Erhardt, Julian Allgeier, Didem Saka, Nirali Donga, Jens Neumann, Christian M. Lange, Alexander L. Gerbes

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Abstract

Background and Aims

Drug-induced liver injury (DILI) due to metamizole has gained increasing attention. Causality assessment remains a challenge, especially in patients with co-medications. We therefore aimed to further characterise metamizole DILI cases.

Methods

The data of patients with metamizole intake from our prospective study on acute liver injury with potential drug-related causes were analysed. Diagnosis and causality assessment were based on a thorough work-up and long-term follow-up.

Results

DILI was associated with metamizole in 61 of 324 DILI patients (prevalence 18.8%). A highly characteristic clinical pattern was observed in 43 of the 61 patients, characterised by marked elevation of transaminases peaking at the time of DILI recognition and a more pronounced increase of bilirubin within the first 3 days of clinical presentation. Patients fitting this picture had higher rates of jaundice, coagulopathy, and acute liver failure, however outcomes did not differ significantly when compared to non-metamizole DILI and autoimmune hepatitis (AIH) patients. Overall, fatal adverse outcomes defined by death or liver transplantation were observed in 13.1% of metamizole DILI patients. On multivariate analysis, only aspartate aminotransferase (AST) and INR were independently associated with a fatal adverse outcome. INR, in particular, performed better than Hy's law, bilirubin, transaminases, and the model for end-stage liver disease (MELD), with a c-statistic of 0.85 (95% CI: 0.70–1.0). At a cut-off of ≥ 2.1, sensitivity and specificity for a fatal adverse outcome were 75% and 96%, respectively.

Conclusions

Metamizole DILI can present with a characteristic pattern that can help clinicians to identify metamizole as the causative agent. Outcome, however, is not associated with this clinical picture and should rather be predicted by INR at onset.

Trial Registration

ClinicalTrials.gov identifier: NCT 02353455

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甲咪唑引起的药物性肝损伤：一种特征性损伤模式的鉴定。

背景与目的：安硝唑引起的药物性肝损伤（DILI）越来越受到人们的关注。因果关系评估仍然是一个挑战，特别是在联合用药的患者中。因此，我们的目的是进一步表征元氨唑DILI病例。方法：对前瞻性研究中可能与药物相关的急性肝损伤患者服用甲硝唑的资料进行分析。诊断和因果关系评估基于彻底的检查和长期随访。结果：324例DILI患者中，61例DILI与安咪唑相关（患病率18.8%）。在61例患者中有43例观察到高度特征性的临床模式，其特征是在DILI识别时转氨酶显著升高，在临床表现的前3天内胆红素明显升高。符合这种情况的患者黄疸、凝血功能障碍和急性肝衰竭的发生率较高，但与非metamizole DILI和自身免疫性肝炎（AIH）患者相比，结果没有显着差异。总体而言，13.1%的metamizole DILI患者观察到死亡或肝移植定义的致命不良结局。在多变量分析中，只有天冬氨酸转氨酶（AST）和INR与致命不良结局独立相关。尤其是INR，其表现优于Hy定律、胆红素、转氨酶和终末期肝病（MELD）模型，c统计量为0.85 （95% CI: 0.70-1.0）。在临界值≥2.1时，致命不良结局的敏感性和特异性分别为75%和96%。结论：Metamizole DILI可以呈现一种特征模式，可以帮助临床医生确定Metamizole是病原体。然而，结果与这种临床表现无关，而应该通过发病时的INR来预测。试验注册：ClinicalTrials.gov标识符：NCT02353455。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.