2026-07-21T14:26:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/170532025-05-29T07:28:41Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc 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 author 2013-07 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. 10.1371/journal.pone.0068111 1932-6203 PloS One http://hdl.handle.net/10668/1272 23874514 http://hdl.handle.net/20.500.12105/17053 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.