TY - JOUR
T1 - Clinical Characteristics and Outcome of Drug-Induced Liver Injury in the Older Patients:
T2 - From the Young-Old to the Oldest-Old
AU - Weersink, Rianne A.
AU - Alvarez-Alvarez, Ismael
AU - Medina-Cáliz, I.
AU - Sanabria-Cabrera, Judith
AU - Robles Díaz, M.
AU - Ortega Alonso, A.
AU - García Cortés, M.
AU - Bonilla, Elvira
AU - Niu, Hao
AU - Soriano, German
AU - Jimenez-Perez, Miguel
AU - Hallal, Hacibe
AU - Blanco, Sonia
AU - Kaplowitz, Neil
AU - Lucena, M. I.
AU - Andrade, Raúl J.
AU - Andrade, R. J.
AU - Stephens, C.
AU - García Cortés, M.
AU - Robles Díaz, M.
AU - Ortega Alonso, A.
AU - Pinazo, J.
AU - García Muñoz, B.
AU - Alcántara, R.
AU - Hernández, A.
AU - García-Escaño, M. D.
AU - Medina-Cáliz, I.
AU - Sanabria-Cabrera, J.
AU - Alvarez-Alvarez, I.
AU - Bonilla, E.
AU - Niu, H.
AU - Di-Zeo, D.
AU - Del Campo, E.
AU - Jiménez Pérez, M.
AU - González Grande, R.
AU - López Ortega, S.
AU - Santaella, I.
AU - Rojas, A.
AU - Soriano, G.
AU - Antonijoan Arbos, R. M.
AU - Montané, E.
AU - Sánchez Delgado, J.
AU - Vergara Gómez, M.
AU - García Oltra, E.
N1 - Publisher Copyright:
© 2020 The Authors. Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85097053232&partnerID=8YFLogxK
U2 - 10.1002/cpt.2108
DO - 10.1002/cpt.2108
M3 - Article
AN - SCOPUS:85097053232
SN - 0009-9236
VL - 109
SP - 1147
EP - 1158
JO - Clinical Pharmacology and Therapeutics
JF - Clinical Pharmacology and Therapeutics
IS - 4
ER -