HLA Alleles Influence the Clinical Signature of Amoxicillin-Clavulanate Hepatotoxicity
Por:
Stephens, C, Lopez-Nevot, MA, Ruiz-Cabello, F, Ulzurrun, E, Soriano, G, Romero-Gomez, M, Moreno-Casares, A, Lucena, MI, Andrade, RJ
Publicada:
9 jul 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.
Filiaciones:
Stephens, C:
Univ Malaga, Unidad Gest Clin Enfermedades Digest, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin,Hosp Univ Virgen Victoria, E-29071 Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Lopez-Nevot, MA:
Univ Granada, Hosp Univ Virgen Nieves, Dept Bioquim & Biol Mol Inmunol 3, Granada, Spain
Ruiz-Cabello, F:
Univ Granada, Hosp Univ Virgen Nieves, Dept Bioquim & Biol Mol Inmunol 3, Granada, Spain
Red Genom Canc, Madrid, Spain
Ulzurrun, E:
Univ Malaga, Unidad Gest Clin Enfermedades Digest, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin,Hosp Univ Virgen Victoria, E-29071 Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Soriano, G:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Serv Gastroenterol, E-08193 Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Romero-Gomez, M:
Univ Seville, Hosp Univ Valme, Andalucia Tech, Unidad Gest Clin Enfermedades Digest, Seville, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Moreno-Casares, A:
Univ Granada, Hosp Univ Virgen Nieves, Dept Bioquim & Biol Mol Inmunol 3, Granada, Spain
Lucena, MI:
Univ Malaga, Unidad Gest Clin Enfermedades Digest, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin,Hosp Univ Virgen Victoria, E-29071 Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Andrade, RJ:
Univ Malaga, Unidad Gest Clin Enfermedades Digest, Inst Invest Biomed Malaga IBIMA, Serv Farmacol Clin,Hosp Univ Virgen Victoria, E-29071 Malaga, Spain
Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Spain
Gold, Green Published
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