Drug Induced Liver Injury in Geriatric Patients Detected by a Two-Hospital Prospective Pharmacovigilance Program: A Comprehensive Analysis Using the Roussel Uclaf Causality Assessment Method

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.

Utility of Lymphocyte Transformation Test for Assisting Updated Roussel Uclaf Causality Assessment Method in Drug-Induced Liver Injury: A Case-Control Study

“…However, 62.5% of the DILI cases that caused hospitalization were moderate or severe cases and with longer latencies. These data are consistent with previous DILI publications of the group (Pedraza et al, 2020;Delgado et al, 2021).…”

Characterisation of Drug-Induced Liver Injury in Patients with COVID-19 Detected by a Proactive Pharmacovigilance Program from Laboratory Signals

“…In a study performed by Cai et al, (2020) [ 21 ], the median age in patients who had altered liver enzymes or liver damage (defined as ALT or AST > 3 ULN or GGT or total bilirubin > 2 ULN) was 53 (42–64) years, with a value of p = 0.04, compared with those who did not develop liver alterations, whose median age was 47 (33–59). In another study with the same pharmacovigilance program, older men experienced greater DILI severity, which was associated with higher alcohol and low albumin levels in this group [ 22 ]. The frequency of other metabolic risk factors (diabetes mellitus, hypertension, dyslipidaemia) in the DILI cohort was no higher than in the hospital’s COVID-19 cohort [ 23 ].…”

Improving functional outcomes and quality of life in an elderly woman with sarcopenia and spinal Tuberculosis: A case report

“…A different approach is required to treat this patient. Malnutrition, being female, and older age increased the risk of AT-DILI in these patients (27,28). In our patient, it was necessary to ensure adherence to ATT treatment, adequate nutritional intake, and good wound care.…”