Characterization of drug-induced liver injury associated with drug reaction with eosinophilia and systemic symptoms in two prospective DILI registries
Medina-Cáliz, Inmaculada (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Sanabria-Cabrera, Judith (Instituto de Investigación Biomédica de Málaga)
Villanueva-Paz, Marina (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Aukštikalnė, Lauryna (Lithuanian University of Health Sciences)
Stephens, Camilla (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Robles-Díaz, Mercedes (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Pinazo-Bandera, José M. (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
García-Cortes, Miren (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Conde, Isabel (Hospital Universitari I Politècnic La Fe)
Soriano, German (Institut d'Investigació Biomèdica Sant Pau)
Bessone, Fernando (Hospital Provincial del Centenario)
Hernandez, Nelia (Hospital de Clínicas)
Nunes, Vinicius (Hospital Universitário Prof. Edgard Santos-UFBA)
Paraná, Raymundo (Hospital Universitário Prof. Edgard Santos-UFBA)
Lucena, M. Isabel (Universidad de Málaga)
Andrade, Raúl J. (Universidad de Málaga)
Niu, Hao (Universidad de Málaga)
Alvarez-Alvarez, Ismael (Universidad de Málaga)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI21/01248 Instituto de Salud Carlos III PI19/00883
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Drug-induced liver injury ; Drug reaction with eosinophilia and systemic symptoms ; Hepatotoxicity ; Hypersensitivity features ; Severe cutaneous adverse reaction
Publicat a:	Archives of Toxicology, Vol. 98 (december 2023) , p. 303-325, ISSN 1432-0738

DOI: 10.1007/s00204-023-03630-0
PMID: 38051367

23 p, 630.8 KB

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