RT Journal Article
T1 HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity.
A1 Stephens, Camilla
A1 López-Nevot, Miguel-Ángel
A1 Ruiz-Cabello, Francisco
A1 Ulzurrun, Eugenia
A1 Soriano, Germán
A1 Romero-Gómez, Manuel
A1 Moreno-Casares, Antonia
A1 Lucena, M Isabel
A1 Andrade, Raul J
K1 Combinación Amoxicilina-Clavulanato de Potasio
K1 Enfermedad Hepática Inducida por Drogas
K1 Predisposición Genética a la Enfermedad
K1 Haplotipos
K1 Fenotipo
K1 Inmunidad Adaptativa
K1 Antibacterianos
K1 Genes Clase I del Complejo de Histocompatibilidad (MHC)
K1 Genes Clase II del Complejo de Histocompatibilidad (MHC)
K1 Antígenos HLA-A
K1 Antígenos HLA-DQ
K1 Antígenos HLA-DR
K1 Cadenas beta de HLA-DR
K1 Factores de Riesgo
K1 España
AB BACKGROUND AND AIMThe 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.METHODSHigh resolution genotyping of HLA loci A, B, C, DRB1 and DQB1 was performed in 75 AC DILI cases and 885 controls.RESULTSThe 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).CONCLUSIONSHLA class I and II alleles influence the AC DILI signature with regards to phenotypic expression, latency presentation and severity in Spanish patients.
PB Public Library of Science
YR 2013
FD 2013-07
LK http://hdl.handle.net/10668/1272
UL http://hdl.handle.net/10668/1272
LA en
NO Stephens C, López-Nevot MÁ, Ruiz-Cabello F, Ulzurrun E, Soriano G, Romero-Gómez M, et al. HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity. PLoS ONE. 2013; 8(7):e68111
NO Journal Article;
DS RISalud
RD Apr 18, 2025