2026-07-21T14:26:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/170532025-05-29T07:28:41Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Stephens, Camilla
author
López-Nevot, Miguel-Ángel
author
Ruiz-Cabello, Francisco
author
Ulzurrun, Eugenia
author
Soriano, Germán
author
Romero-Gómez, Manuel
author
Moreno-Casares, Antonia
author
Lucena, M Isabel
author
Andrade, Raul J
authoraffiliation
[Stephens,C; Ulzurrun,E; Lucena,MI; Andrade,RJ] Unidad de Gestión Clínica de Enfermedades Digestivas, Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria. Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Spain. [López-Nevot,MA; Ruiz-Cabello,F; Moreno-Casares,A] Departamento de Bioquímica y Biología Molecular III/Inmunología, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Spain. [Soriano,G] Servicio de Gastroenterología, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. [Romero-Gómez,M] Unidad de Gestión Clínica de Enfermedades Digestivas, Hospital Universitario de Valme, Universidad de Sevilla, Andalucía Tech, Sevilla, Spain. [Stephens,C; Ulzurrun,E; Soriano,G; Romero-Gómez,M; Lucena,MI; Andrade,RJ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain. [Ruiz-Cabello,F] Red Genómica del Cáncer, Madrid, Spain.
2024-01-15T18:17:02Z
2024-01-15T18:17:02Z
2013-07
10.1371/journal.pone.0068111
1932-6203
PloS One
http://hdl.handle.net/10668/1272
23874514
http://hdl.handle.net/20.500.12105/17053
BACKGROUND AND AIM: The genotype-phenotype interaction in drug-induced liver injury (DILI) is a subject of growing interest. Previous studies have linked amoxicillin-clavulanate (AC) hepatotoxicity susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class I and II alleles and AC DILI with regards to phenotypic characteristics, severity and time to onset in Spanish AC hepatotoxicity cases. METHODS: High resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls. RESULTS: The distributions of class I alleles A*3002 (P/Pc = 2.6E-6/5E-5, OR 6.7) and B*1801 (P/Pc = 0.008/0.22, OR 2.9) were more frequently found in hepatocellular injury cases compared to controls. In addition, the presence of the class II allele combination DRB1*1501-DQB1*0602 (P/Pc = 5.1E-4/0.014, OR 3.0) was significantly increased in cholestatic/mixed cases. The A*3002 and/or B*1801 carriers were found to be younger (54 vs 65 years, P = 0.019) and were more frequently hospitalized than the DRB1*1501-DQB1*0602 carriers. No additional alleles outside those associated with liver injury patterns were found to affect potential severity as measured by Hy's Law criteria. The phenotype frequencies of B*1801 (P/Pc = 0.015/0.42, OR 5.2) and DRB1*0301-DQB1*0201 (P/Pc = 0.0026/0.07, OR 15) were increased in AC DILI cases with delayed onset compared to those corresponding to patients without delayed onset, while the opposite applied to DRB1*1302-DQB1*0604 (P/Pc = 0.005/0.13, OR 0.07). CONCLUSIONS: HLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
eng
Combinación Amoxicilina-Clavulanato de Potasio
Enfermedad Hepática Inducida por Drogas
Predisposición Genética a la Enfermedad
Haplotipos
Fenotipo
Inmunidad Adaptativa
Antibacterianos
Genes Clase I del Complejo de Histocompatibilidad (MHC)
Genes Clase II del Complejo de Histocompatibilidad (MHC)
Antígenos HLA-A
Antígenos HLA-DQ
Antígenos HLA-DR
Cadenas beta de HLA-DR
Factores de riesgo
España
HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity.
research article