The Impact of Polypharmacy Therapeutic classes on Mortality Outcomes in Patients with Chronic Liver Disease

Despite its pivotal role in drug metabolism, the exact consequences of rising medica-tions count from various therapeutic drug classes on mortality outcomes amongst patients with chronic liver disease remains unexplored. In this study, we investigated the effect of different polypharmacy phenotypes on clinical outcomes including the length of hospitalization, the need for intensive care admission, and mortality in patients with chronic liver disease (CLD). Methods: This retrospective cohort study examined the impact of various polypharmacy phenotypes on clinical outcomes of patients receiving care at tertiary care centres within the Weill Cornell Medi-cine-affiliated Hamad Medical Corporation, Doha Qatar diagnosed with CLD be-tween October 2018 to August 2021. Primary outcomes include all-cause mortality, length of hospitalization, and need for intensive care unit admission. Multivariable regression models were used to assess the associations between the number of liv-er-related and non-liver-related polypharmacy and these clinical outcomes. Results: In this retrospective cohort study, 3331 participants with a median age of 50 years (interquartile range [IQR] 40–63) were included, of which 71.0% (n = 2 366) were males. The total duration of follow-up for the whole cohort was 42 772.6 per-son-days. The median length of stay (LOS) was 5.0 (0.5, 13.6) days, with 762 (22.9%) deaths among those hospitalized. About 46.2% of the study participants were on guideline-directed therapy CLD drugs. Patients with polypharmacy inclusive of liver-related drugs had a higher survival over time compared to the group without polypharmacy (log-rank p< 0.001). Each additional CLD drug is associated with a 51% reduction in mortality risk (hazard ratio [HR] 0.49, 95% CI 0.38–0.62). Conclusion: In a hospitalized cohort of patients with CLD, polypharmacy comprising of medications specific for CLD or its complications was associated with reduced all-cause mortality. However, the role of non-liver-related medications in this context remains unclear, and it is uncertain how the primary cause of liver disease could have potentially impacted these outcomes. Further studies exploring these factors are needed to better inform clinical decision-making regarding polypharmacy management in this patient population