Laura Pedraza1, Olga Laosa1,2, Leocadio Rodríguez-Mañas2,3, Diego F Gutiérrez-Romero4, Jesús Frías5, José Antonio Carnicero1,2, Elena Ramírez5,6. 1. Geriatric Research Group, Biomedical Research Foundation at Getafe University Hospital, Getafe, Spain. 2. Centre of Network Biomedical Research on Frailty and Healthy Ageing (CIBERFES), Institute of Health Carlos III., Madrid, Spain. 3. Division of Geriatrics, University Hospital of Getafe, Getafe, Spain. 4. Radiology departments, Virgen del Mar Hospital, Madrid, Spain. 5. Clinical Pharmacology departments, La Paz University Hospital, IdiPAZ, School of Medicine, Autonomous University of Madrid, Madrid, Spain. 6. Clinical pharmacology department, University Hospital La Paz, La Paz, Spain.
Abstract
Background/aim: A prospective evaluation of drug-induced liver injury (DILI) in two tertiary hospitals was conducted through a pharmacovigilance program from laboratory signals at hospital (PPLSH) to determine the principal characteristics of DILI in patients older than 65 years, a growing age group worldwide, which is underrepresented in the literature on DILI. Methods: All DILI in patients older than 65 years detected by PPLSH in two hospitals were followed up for 8 years in the La Paz Hospital and 2 years in the Getafe Hospital. A descriptive analysis was conducted that determined the causality of DILI and suspected drugs, the incidence of DILI morbidities, DILI characteristics, laboratory patterns, evolution and outcomes. Results: 458 DILI cases in 441 patients were identified, 31.0% resulting in hospitalisation and 69.0% developing during hospitalisation. The mean age was 76.61 years old (SD, 7.9), and 54.4% were women. The DILI incidence was 76.33/10,000 admissions (95%CI 60.78-95.13). Polypharmacy (taking >4 drugs) was present in 86.84% of patients, 39.68% of whom took >10 drugs. The hepatocellular phenotype was the most frequent type of DILI (53.29%), a higher proportion (65%) had a mild severity index, and, in 55.2% of the evaluated drugs the RUCAM indicated that the causal relationship was highly probable. The most frequently employed drugs were paracetamol (50-cases), amoxicillin-clavulanate (42-cases) and atorvastatin (37-cases). The incidence rate of in-hospital DILI per 10,000 DDDs was highest for piperacillin-tazobactam (66.96/10,000 DDDs). A higher risk of in-hospital DILI was associated with the therapeutic chemical group-J (antiinfectives for systemic use) (OR, 2.65; 95%CI 1.58-4.46) and group-N (central nervous system drugs) (OR, 2.33; 95%CI 1.26-4.31). The patients taking >4 medications presented higher maximum creatinine level (OR, 2.01; 95%CI 1.28-3.15), and the patients taking >10 medications had a higher use of group J drugs (OR, 2.08; 95%IC 1.31-3.32). Conclusion: The incidence rate of DILI in the patients older than 65 years was higher than expected. DILI in elderly patients is mild, has a good outcome, has a hepatocellular pattern, develops during hospitalisation, and prolongs the hospital stay. Knowing the DILI incidence and explanatory factors will help improve the therapy of the elderly population.
Background/aim: A prospective evaluation of drug-induced liver injury (DILI) in two tertiary hospitals was conducted through a pharmacovigilance program from laboratory signals at hospital (PPLSH) to determine the principal characteristics of DILI in patients older than 65 years, a growing age group worldwide, which is underrepresented in the literature on DILI. Methods: All DILI in patients older than 65 years detected by PPLSH in two hospitals were followed up for 8 years in the La Paz Hospital and 2 years in the Getafe Hospital. A descriptive analysis was conducted that determined the causality of DILI and suspected drugs, the incidence of DILI morbidities, DILI characteristics, laboratory patterns, evolution and outcomes. Results: 458 DILI cases in 441 patients were identified, 31.0% resulting in hospitalisation and 69.0% developing during hospitalisation. The mean age was 76.61 years old (SD, 7.9), and 54.4% were women. The DILI incidence was 76.33/10,000 admissions (95%CI 60.78-95.13). Polypharmacy (taking >4 drugs) was present in 86.84% of patients, 39.68% of whom took >10 drugs. The hepatocellular phenotype was the most frequent type of DILI (53.29%), a higher proportion (65%) had a mild severity index, and, in 55.2% of the evaluated drugs the RUCAM indicated that the causal relationship was highly probable. The most frequently employed drugs were paracetamol (50-cases), amoxicillin-clavulanate (42-cases) and atorvastatin (37-cases). The incidence rate of in-hospital DILI per 10,000 DDDs was highest for piperacillin-tazobactam (66.96/10,000 DDDs). A higher risk of in-hospital DILI was associated with the therapeutic chemical group-J (antiinfectives for systemic use) (OR, 2.65; 95%CI 1.58-4.46) and group-N (central nervous system drugs) (OR, 2.33; 95%CI 1.26-4.31). The patients taking >4 medications presented higher maximum creatinine level (OR, 2.01; 95%CI 1.28-3.15), and the patients taking >10 medications had a higher use of group J drugs (OR, 2.08; 95%IC 1.31-3.32). Conclusion: The incidence rate of DILI in the patients older than 65 years was higher than expected. DILI in elderly patients is mild, has a good outcome, has a hepatocellular pattern, develops during hospitalisation, and prolongs the hospital stay. Knowing the DILI incidence and explanatory factors will help improve the therapy of the elderly population.
Authors: Amelia Rodríguez; Irene García-García; Lucía Martínez de Soto; Arturo Gómez López De Las Huertas; Alberto M Borobia; Andrea González-Torbay; Ibtissam Akatbach-Bousaid; Miguel González-Muñoz; Elena Ramírez Journal: Front Pharmacol Date: 2022-03-10 Impact factor: 5.810