A new framework for advancing in drug‐induced liver injury research. The Prospective European DILI Registry

© 2022 The Authors. Liver International published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Background & aims: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported. Methods: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021. DILI cases or non-DILI acute liver injury controls following causality assessment were enrolled. Results: Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre-existing liver disease. DILI cases and non-DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin-clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug-induced autoimmune-like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver-related death), and another six received liver transplantation. Conclusions: In this first multi-national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI.Set up of the Prospective European Drug-Induced Liver Injury Registry (Pro-Euro-DILI Registry) was supported by an award to RJA and GPA from the EASL Registry Research Grants Programme. JIG and GPA are supported by National Institute of Health Research Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Biomedical Research Centre [BRC-1215-20003]. RJA and MIL receive support from AEMPS. IAA holds a Sara Borrell contract (CD20/00083) funded by ISCiii. CIBERehd is funded by ISCiii. This article is based upon work from COST Action “CA17112 - Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology). www.cost.eu. All authors of this manuscript are members of COST Action CA17112. The Pro-Euro-DILI is a part of the Transbioline Consortium. The TransBioLine project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 821283. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA.