Clinical Characteristics and Outcome of Drug-Induced Liver Injury in the Older Patients: From the Young-Old to the Oldest-Old


Por: Weersink, RA, Alvarez-Alvarez, I, Medina-Caliz, I, Sanabria-Cabrera, J, Robles-Diaz, M, Ortega-Alonso, A, Garcia-Cortes, M, Bonilla, E, Niu, H, Soriano, G, Jimenez-Perez, M, Hallal, H, Blanco, S, Kaplowitz, N, Lucena, MI, Andrade, RJ, Antonijoan Arbós R.M., Gonzalez-Gallego, J.

Publicada: 1 abr 2021 Ahead of Print: 1 dic 2020
Resumen:
Older patients with hepatotoxicity have been scarcely studied in idiosyncratic drug-induced liver injury (DILI) cohorts. We sought the distinctive characteristics of DILI in older patients across age groups. A total of 882 DILI patients included in the Spanish DILI Registry (33% >= 65 years) were categorized according to age: "young" (< 65 years); "young-old" (65-74 years); "middle-old" (75-84 years); and "oldest-old" (>= 85 years). All elderly groups had an increasingly higher comorbidity burden (P < 0.001) and polypharmacy (P < 0.001). There was a relationship between jaundice and hospitalization (P < 0.001), and both were more prevalent in the older age groups, especially in the oldest-old (88% and 69%, respectively), and the DILI episode was more severe (P = 0.029). The proportion of females decreased across age groups from the young to the middle-old, yet in the oldest-old there was a distinct female predominance. Pattern of liver injury shifted towards cholestatic with increasing age among top culprit drugs amoxicillin-clavulanate, atorvastatin, levofloxacin, ibuprofen, and ticlopidine. The best cutoff point for increased odds of cholestatic DILI was 65 years. Older patients had increased non-liver-related mortality (P = 0.030) as shown by the predictive capacity of the Model for End-Stage Liver Disease score (odds ratio (OR) = 1.116; P < 0.001), and comorbidity burden (OR = 4.188; P = 0.001) in the 6-month mortality. Older patients with DILI exhibited an increasingly predominant cholestatic phenotype across a range of culprit drugs, other than amoxicillin-clavulanate, with increased non-liver-related mortality and require a different approach to predict outcome. The oldest DILI patients exhibited a particular phenotype with more severe DILI episodes and need to be considered when stratifying older DILI populations.

Filiaciones:
Weersink, RA:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

 Deventer Hosp, Dept Clin Pharm, Deventer, Netherlands

Alvarez-Alvarez, I:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

Medina-Caliz, I:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

Sanabria-Cabrera, J:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

 SCReN Spanish Clin Res Network, Platform Clin Res & Clin Trials IBIMA, Madrid, Spain

Robles-Diaz, M:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

Ortega-Alonso, A:
 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Serv Aparato Digest, Malaga, Spain

Garcia-Cortes, M:
 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Serv Aparato Digest, Malaga, Spain

Bonilla, E:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

Niu, H:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

Soriano, G:
 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

 Hosp Santa Creu & Sant Pau, Serv Aparato Digest, Barcelona, Spain

Jimenez-Perez, M:
 Complejo Hosp Reg Malaga, UGC Aparato Digest, Malaga, Spain

Hallal, H:
 Hosp Gen Univ JM Morales Meseguer, Serv Aparato Digest, Murcia, Spain

Blanco, S:
 Hosp Univ Basurto, Serv Aparato Digest, Bilbao, Spain

Kaplowitz, N:
 Univ Southern Calif, Res Ctr Liver Dis, Keck Sch Med, Los Angeles, CA 90007 USA

Lucena, MI:
 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biorned Malaga IBIMA, Serv Farmacol Clin, Malaga, Spain

 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

 SCReN Spanish Clin Res Network, Platform Clin Res & Clin Trials IBIMA, Madrid, Spain

Andrade, RJ:
 Carlos III Hlth Inst, Ctr Hepat & Digest Dis CIBERehd, Biomed Res Network, Madrid, Spain

 Univ Malaga, Hosp Univ Virgen Victoria, Inst Invest Biomed Malaga IBIMA, Serv Aparato Digest, Malaga, Spain

Antonijoan Arbós R.M.:
 Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain

Gonzalez-Gallego, J.:
 Universidad de León, Leon, Spain
ISSN: 00099236
Editorial
WILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA, Estados Unidos America
Tipo de documento: Article
Volumen: 109 Número: 4
Páginas: 1147-1158
WOS Id: 000595840200001
ID de PubMed: 33179256
imagen Green Accepted

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