Volume 109, Issue 4 p. 1147-1158
Article

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

Rianne A. Weersink

Rianne A. Weersink

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

Department of Clinical Pharmacy, Deventer Hospital, Deventer, The Netherlands

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Ismael Alvarez-Alvarez

Ismael Alvarez-Alvarez

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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Inmaculada Medina-Cáliz

Inmaculada Medina-Cáliz

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

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Judith Sanabria-Cabrera

Judith Sanabria-Cabrera

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

Platform for Clinical Research and Clinical Trials IBIMA, SCReN (Spanish Clinical Research Network), Madrid, Spain

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Mercedes Robles-Díaz

Mercedes Robles-Díaz

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

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Aida Ortega-Alonso

Aida Ortega-Alonso

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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Miren García-Cortés

Miren García-Cortés

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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Elvira Bonilla

Elvira Bonilla

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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Hao Niu

Hao Niu

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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German Soriano

German Soriano

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

Servicio Aparato Digestivo, Hospital Santa Creu I Sant Pau, Barcelona, Spain

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Miguel Jimenez-Perez

Miguel Jimenez-Perez

UGC Aparato Digestivo, Complejo Hospitalario Regional de Málaga, Málaga, Spain

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Hacibe Hallal

Hacibe Hallal

Servicio Aparato Digestivo, Hospital General Universitario J.M. Morales Meseguer, Murcia, Spain

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Sonia Blanco

Sonia Blanco

Servicio de Aparato Digestivo, Hospital Universitario Basurto, Bilbao, Spain

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Neil Kaplowitz

Neil Kaplowitz

Keck School of Medicine, University of Southern California Research Center for Liver Diseases, Los Angeles, California, USA

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M. Isabel Lucena

Corresponding Author

M. Isabel Lucena

Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

Platform for Clinical Research and Clinical Trials IBIMA, SCReN (Spanish Clinical Research Network), Madrid, Spain

Correspondence: M. Isabel Lucena ([email protected])

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Raúl J. Andrade

Raúl J. Andrade

Biomedical Research Network Center for Hepatic and Digestive Diseases (CIBERehd), Carlos III Health Institute, Madrid, Spain

Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain

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First published: 11 November 2020
Citations: 16

Abstract

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.

Conflict of Interests

The authors declared no competing interests for this work.