Medication burden and FIB-4-defined risk classification in older adults: a real-world study

Abstract Introduction Non-invasive fibrosis scores such as the Fibrosis-4 (FIB-4) index are widely used in routine clinical practice to stratify liver fibrosis risk. However, the interpretation of FIB-4 in older adults is challenging because age is incorporated directly into its calculation and polypharmacy is highly prevalent in this population. This study aimed to evaluate the association between total medication burden and FIB-4-defined risk classification in a real-world internal medicine population, with particular emphasis on patients aged 65 years and older. Methods In this retrospective observational study, 300 adult patients consecutively evaluated in an internal medicine outpatient clinic were included. Demographic characteristics, body mass index, laboratory parameters required for FIB-4 calculation, and medication data were obtained from electronic medical records. Polypharmacy was defined as the concurrent use of five or more active pharmacological agents. Age-adjusted lower thresholds of ≥ 1.30 in patients aged < 65 years and ≥ 2.0 in patients aged ≥ 65 years were used to define above-threshold FIB-4 classification. Comparisons were performed between age groups and, within the older population, according to polypharmacy status. Among patients aged ≥ 65 years, age-inclusive and age-excluded multivariable logistic regression models were evaluated. Results Older patients exhibited a significantly higher total medication burden and higher FIB-4 scores than younger patients. Within the ≥ 65-year age group, polypharmacy was not associated with significantly higher FIB-4 scores or a higher prevalence of above-threshold FIB-4 classification. In the age-inclusive model, total medication burden was not independently associated with above-threshold FIB-4 classification (aOR per active agent: 0.93, 95% CI: 0.78–1.11; p = 0.435). This finding remained unchanged in the age-excluded sensitivity model (aOR per active agent: 1.01, 95% CI: 0.87–1.18; p = 0.882). The age coefficient was not interpreted biologically because age is an explicit component of the FIB-4 equation. Conclusion Among older adults, polypharmacy status was not associated with FIB-4 score or above-threshold FIB-4 classification, and total medication burden was not independently associated with above-threshold FIB-4 classification in either the age-inclusive or age-excluded model. These findings relate to a screening-based risk classification and should not be interpreted as evidence regarding confirmed liver fibrosis or the hepatic effects of individual medications. Because age is incorporated directly into the FIB-4 equation, its association with the outcome should not be interpreted as evidence that age is an independent biological determinant of liver fibrosis.