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

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