RT Journal Article
T1 The influence of drug properties and host factors on delayed onset of symptoms in drug‐induced liver injury.
A1 González-Jiménez, Andrés
A1 McEuen, Kristin
A1 Chen, Minjun
A1 Suzuki, Ayako
A1 Robles‑Diaz, Mercedes
A1 Medina-Cáliz, Inmaculada
A1 Bessone, Fernando
A1 Hernandez, Nelia
A1 Arrese, Marco
A1 Parana, Raymundo
A1 Lucena-González, María Isabel
A1 Stephens, Camilla
A1 Andrade-Bellido, Raúl Jesús
K1 Hepatotoxicidad
K1 Medicamentos - Efectos secundarios
K1 Interacciones medicamentosas
K1 Minería de datos
AB Background & Aims: Most patients with drug‐induced liver injury (DILI) manifestclinical symptoms while on therapy, while some patients manifest days or weeks afterdrug cessation (delayed onset). This challenges DILI causality assessment and diagnosis.Factors contributing to the delayed onset phenotype are currently unknown. We exploredfactors contributing to delayed onset of DILI by analysing culprit drug properties, hostfactors and their interactions in a large patient population from the Spanish DILI Registry.Methods: Clinical information from 388 patients (69 presented delayed onset) and drugproperties of 43 causative drugs (45 active ingredients) were analysed. A two-tierregression‐based model was used to assess host/drug interactions affecting the probabilityof delayed onset.
AB Results: Antibacterial and anti‐inflammatory drugs accounted for the delayed onset cases.Drug property of <50% hepatic metabolism (odds ratio [OR] 11.06, 95% confidenceinterval [95% CI]: 4.4‐32.2, P = 0.0003), daily dose ≥1000 mg (OR: 2.77, 95% CI: 1.3‐6.1, P = 0.0063) and the absence of pre‐existing conditions in a patient (OR: 2.55, 95%CI: 1.3‐4.9, P = 0.0043) were independently associated with delayed onset. The findingswere consistent when externally validated using Latin American DILI Network cases (N= 131). Likewise, drug properties of mitochondrial liability and Pauling electronegativitywere associated with delayed onset, but dependent on specific host factors such as age,sex and pre‐existing cardiac diseases.Conclusions: This study demonstrated that delayed onset, a specific DILI phenotype, isexplained by complex interactions among drug properties and host factors and providedmechanistic hypotheses for future studies. These findings can help improve the diagnosticcapability and causality assessment.
PB Wiley
YR 2019
FD 2019-02
LK https://hdl.handle.net/10630/40273
UL https://hdl.handle.net/10630/40273
LA eng
NO Gonzalez-Jimenez A, McEuen K, Chen M, Suzuki A, Robles-Diaz M, Medina-Caliz I, Bessone F, Hernandez N, Arrese M, Parana R, Lucena MI, Stephens C, Andrade RJ. The influence of drug properties and host factors on delayed onset of symptoms in drug-induced liver injury. Liver International 2019 Feb;39(2):401-410
NO https://openpolicyfinder.jisc.ac.uk/id/publication/11895
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026