The FraiLtx Study Protocol: A Prospective, Single-Center Observational Study on Frailty, Systemic Inflammation, and Monocyte Subsets in Liver Transplant Candidates

Introduction: Frailty is a multidimensional syndrome characterized by diminished physiological reserve and increased susceptibility to stressors, resulting in poor perioperative outcomes. While commonly associated with elderly patients, frailty is increasingly recognized in liver transplant candidates, where it significantly affects morbidity and mortality. The pathophysiological mechanisms underlying frailty in this population remain poorly understood. However, evidence from other distinct patient groups suggests that frailty is linked to a distinct immunophenotype involving altered monocyte subset distribution and elevated pro-inflammatory cytokines. The FraiLtx study aims to investigate the association between frailty, systemic inflammation, and monocyte subpopulations in liver transplant candidates. Methods and analysis: FraiLtx is a prospective, single-center, observational study. We aim to include 81 patients listed for liver transplantation and a control group of 20 individuals not being listed for liver transplantation. Frailty is assessed using both the Liver Frailty Index (LFI) and the FRAIL Scale. Routine blood sampling is performed to calculate the MELD score (model of end stage liver disease). Furthermore, plasma is isolated for quantification of key pro-inflammatory cytokines, and erythrocyte-lysed whole blood is used for detailed profiling of circulating monocyte subsets by flow cytometry. All participants undergo body composition analysis using whole-body MRI (EchoMRI™). Discussion: Although liver cirrhosis is known to be associated with an altered immune landscape, no studies to date have systematically examined the relationship between frailty and immunophenotype in liver transplant candidates. We hypothesize that frail patients listed for liver transplantation will exhibit a characteristic pattern of systemic inflammation, altered monocyte subset distribution, and distinct body composition features. By elucidating the biological correlates of frailty in this cohort, FraiLtx aims to enhance our understanding of its pathophysiology, improve risk stratification, and support the development of targeted therapeutic strategies for this vulnerable population.