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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
Published on: January 31, 2022
Drug-Induced Liver Injury Caused by Metamizole: Identification of a Characteristic Injury Pattern
Sabine Weber1, Franziska Erhardt1, Julian Allgeier1
1Department of Medicine II, LMU Klinikum, Munich, Germany.
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: NCT02353455.
Insights
Drug-induced liver injury (DILI) from metamizole shows a distinct pattern, aiding diagnosis. However, INR at onset is a better predictor of fatal outcomes than clinical presentation.
Area of Science:
- Hepatology
- Pharmacovigilance
- Clinical Toxicology
Background:
- Drug-induced liver injury (DILI) from metamizole is a growing concern.
- Assessing causality is challenging, particularly with multiple medications.
- This study aimed to further characterize metamizole-induced DILI cases.
Purpose of the Study:
- To characterize the clinical presentation of metamizole-induced DILI.
- To identify predictors of fatal outcomes in metamizole DILI.
- To compare metamizole DILI with other forms of DILI and autoimmune hepatitis.
Main Methods:
- Analysis of data from a prospective study on drug-related acute liver injury.
- Inclusion of patients with documented metamizole intake.
- Diagnosis and causality assessment based on thorough work-up and long-term follow-up.
Main Results:
- Metamizole was associated with DILI in 18.8% of cases.
- A characteristic pattern of elevated transaminases and bilirubin was observed in 43/61 patients.
- International Normalized Ratio (INR) at onset demonstrated high accuracy (c-statistic 0.85) in predicting fatal outcomes, outperforming Hy's law and MELD score.
Conclusions:
- Metamizole DILI exhibits a recognizable clinical pattern useful for identifying the causative agent.
- Fatal outcomes in metamizole DILI are not predicted by the characteristic clinical picture.
- INR at the onset of DILI is a strong independent predictor of fatal adverse outcomes.
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