HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity
Stephens, Camilla (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Lopez Nevot, Miguel Angel (Hospital Universitario Virgen de las Nieves (Granada))
Ruiz-Cabello, Francisco (Hospital Universitario Virgen de las Nieves (Granada))
Ulzurrun, Eugenia (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Soriano, German (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Romero-Gómez, Manuel (Universidad de Sevilla)
Moreno-Casares, Antonia (Hospital Universitario Virgen de las Nieves (Granada))
Lucena, María Isabel (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Andrade, Raúl J. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Universitat Autònoma de Barcelona

Fecha:	2013
Resumen:	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.
Nota:	Altres ajuts: Agencia Española del Medicamento (P10-CTS-6470)
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	PloS one, Vol. 8, Núm. 7 (July 2013) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0068111
PMID: 23874514

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