RT Journal Article
T1 Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries
A1 Medina-Cáliz, Inmaculada
A1 Sanabria-Cabrera, Judith Adriana
A1 Villanueva-Paz, Marina
A1 Aukštikalnė, Lauryna
A1 Stephens, Camilla
A1 Robles-Díaz, María Mercedes
A1 Pinazo-Bandera, José M.
A1 García-Cortés, Miren
A1 Conde, Isabel
A1 Soriano, German
A1 Bessone, Fernando
A1 Hernandez, Nelia
A1 Nunes, Vinicius
A1 Parana, Raymundo
A1 Lucena-González, María Isabel
A1 Andrade, Raúl J.
A1 Álvarez-Álvarez, Ismael
A1 Niu, Hao
K1 Hígado - Enfermedades
AB Idiosyncratic drug-induced liver injury (DILI) associated with drug reactions with eosinophilia and systemic symptoms (DRESS) is poorly characterized among patients of Western countries. We aimed to comprehensively assess the clinical characteristics, outcomes, and causative agents in a prospective, well-vetted cohort of DILI patients with DRESS (DILI-DRESS). We identified 53 DILI-DRESS cases from the Spanish DILI Registry and the Latin American DILI Network. For comparison purposes, we defined a group of DILI patients (n = 881). DILI-DRESS cases were younger (47 vs. 53 years, respectively; p = 0.042) and presented more frequently with cholestatic/mixed damage (p = 0.018). Most DILI-DRESS patients showed moderate liver injury, 13% developed severe damage, and only one patient (with hepatocellular injury due to anti-tuberculosis drugs) progressed to acute liver failure and died. DILI-DRESS cases showed a distinctive causative drug pattern compared to DILI cases. The most frequent drugs were carbamazepine (13%), anti-tuberculosis drugs (13%), amoxicillin-clavulanate (11%), and allopurinol and lamotrigine (7.6% each). Among all cases of DILI due to allopurinol and lamotrigine, 67% presented with a DILI-DRESS phenotype, respectively. Higher total bilirubin (TBL) levels at DILI recognition (odds ratio [OR] 1.23; 95% confidence interval [CI] 1.04–1.45) and absence of eosinophilia (OR 8.77; 95% CI 1.11–69.20) increased the risk for developing a severe-fatal injury in DILI-DRESS patients. DILI-DRESS patients have a more frequent cholestasis/mixed pattern of injury at presentation, with antiepileptics as distinctive causative drug class. Most of the lamotrigine and allopurinol cases present with this phenotype. Higher TBL levels and absence of eosinophilia at DILI recognition are markers of poor outcomes.
PB Springer Nature
YR 2023
FD 2023-12-05
LK https://hdl.handle.net/10630/28660
UL https://hdl.handle.net/10630/28660
LA eng
NO Medina-Cáliz, I., Sanabria-Cabrera, J., Villanueva-Paz, M. et al. Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries. Arch Toxicol 98, 303–325 (2024). https://doi.org/10.1007/s00204-023-03630-0
NO Funding for open access publishing: Universidad Málaga/CBUA. This work was supported by grants from the Instituto de Salud Carlos III, cofounded by Fondo Europeo de Desarrollo Regional (FEDER) (contract numbers: PI21/01248, PI19-00883, PT20/00127, UMA18-FEDERJA-194, PY18-3364), and grants from Consejería de Salud de Andalucía cofounded by FEDER (contract numbers: PEMP-0127-2020, PI-0310-2018) and Agencia Española del Medicamento y Productos Sanitarios. M Villanueva-Paz and I Alvarez-Alvarez hold Sara Borrell research contracts from ISCIII (CD21/00198 and CD20/00083, respectively). J Sanabria-Cabrera holds a Juan Rodés research contract from the National System of Health, ISCIII (JR21/00066). JM Pinazo-Bandera holds a Río Hortega research contract from the National System of Health, ISCIII (CM21/00074). H Niu holds a postdoctoral research contract funded by Junta de Andalucía (POSTDOC_21_00780). SCReN and CIBERehd are funded by ISCIII. This publication is based on work from COST Action CA17112—Prospective European Drug-Induced Liver Injury Network, supported by COST (European Cooperation in Science and Technology); www.cost.eu. The funding sources have no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 4 mar 2026