RT Journal Article
T1 Rechallenge in idiosyncratic drug-induced liver injury: An analysis of cases in two large prospective registries according to existing definitions.
A1 Pinazo-Bandera, José M.
A1 Niu, Hao
A1 Álvarez-Álvarez, Ismael
A1 Medina-Cáliz, Inmaculada
A1 Del Campo-Herrera, Enrique
A1 Ortega-Alonso, Aida
A1 Robles‑Diaz, Mercedes
A1 Hernandez, Nelia
A1 Parana, Raymundo
A1 Nunes, Vinicius
A1 Girala, Marcos
A1 Bessone, Fernando
A1 Lucena-González, María Isabel
A1 Andrade-Bellido, Raúl Jesús
A1 García-Cortés, Miren
K1 Hígado - Heridas y lesiones
K1 Hepatotoxicidad
AB Introduction: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries.Methods: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed.Results: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. Conclusions: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.
PB Elsevier
YR 2024
FD 2024
LK https://hdl.handle.net/10630/37955
UL https://hdl.handle.net/10630/37955
LA eng
NO Pinazo-Bandera JM, Niu H, Alvarez-Alvarez I, Medina-Cáliz I, Del Campo-Herrera E, Ortega-Alonso A, Robles-Díaz M, Hernández N, Paraná R, Nunes V, Girala M, Bessone F, Lucena MI, Andrade RJ, García Cortés M. Rechallenge in idiosyncratic drug-induced liver injury: An analysis of cases in two large prospective registries according to existing definitions. Pharmacol Res. 2024;203:107183
NO Grants from Instituto de Salud Carlos III (ISCIII) cofunded by the European Union: Fondo Europeo de Desarrollo Regional - FEDER (contract numbers: PI21/01248). CIBERehd is funded by ISCIII. JMPB holds a Rio Hortega contract from ISCIII (CM21/00074) and cofounded by the European Union. HN holds a postdoctoral research contract funded by Junta de Andalucía (POSTDOC_21_00780). This project has received funding from the European Horizon´s research and innovation program HORIZON-HLTH-2022-STAYHLTH-02 under agreement No 101095679.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026