2609005115
  • Open Access
  • Study Protocol

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

  • Ole Sattler 1,*,   
  • Anja Bosy-Westphal 2,   
  • Gunnar Elke 3,   
  • Amke Caliebe 4,5,   
  • Christian Peters 6,   
  • Karina Silvana Zitta 1,   
  • Martin Albrecht 1,   
  • Felix Braun 7,   
  • Anna Lulu Homayr 1

Received: 29 Jun 2026 | Revised: 31 Aug 2026 | Accepted: 03 Sep 2026 | Published: 16 Sep 2026

Abstract

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.

References 

  • 1.

    Girish, V.; Mousa, O.Y. Liver Transplantation. In StatPearls [Internet]; StatPearls Publishing: Treasure Island, FL, USA, 2026. Available online: http://www.ncbi.nlm.nih.gov/books/NBK559161/ (accessed on 6 April 2026).

  • 2.

    Devarbhavi, H.; Asrani, S.K.; Arab, J.P.; et al. Global burden of liver disease: 2023 update. J. Hepatol. 2023, 79, 516–537. https://doi.org/10.1016/j.jhep.2023.03.017.

  • 3.

    Sandhu, S.; Goldberg, D. Update on Organ Allocation and Liver Transplantation. Gastroenterol. Hepatol. 2025, 21, 424–430.

  • 4.

    van Vugt, J.L.A.; Alferink, L.J.M.; Buettner, S.; et al. A model including sarcopenia surpasses the MELD score in predicting waiting list mortality in cirrhotic liver transplant candidates: A competing risk analysis in a national cohort. J. Hepatol. 2018, 68, 707–714. https://doi.org/10.1016/j.jhep.2017.11.030.

  • 5.

    Engelmann, C.; Aehling, N.; Schob, S.; et al. Body fat composition determines outcomes before and after liver transplantation in patients with cirrhosis. Hepatol. Commun. 2022, 6, 2198–2209. https://doi.org/10.1002/hep4.1946.

  • 6.

    Cybularz, M.; Wydra, S.; Berndt, K.; et al. Frailty is associated with chronic inflammation and pro-inflammatory monocyte subpopulations. Exp. Gerontol. 2021, 149, 111317. https://doi.org/10.1016/j.exger.2021.111317.

  • 7.

    Murphy, P.; Savage, S.; Zarzaur, B. Impact of Patient Frailty on Morbidity and Mortality after Common Emergency General Surgery Operations. J. Surg. Res. 2020, 247, 95–102. https://doi.org/10.1016/j.jss.2019.10.038.

  • 8.

    Clegg, A.; Young, J.; Iliffe, S.; et al. Frailty in elderly people. Lancet 2013, 381, 752–762. https://doi.org/10.1016/s0140-6736(12)62167-9. Erratum in Lancet 2013, 382, 1328.

  • 9.

    Fried, L.; Tangen, C.; Walston, J.; et al. Frailty in older adults: Evidence for a phenotype. J. Gerontol. A Biol. Sci. Med. Sci. 2001, 56, M146–M156. https://doi.org/10.1093/gerona/56.3.m146.

  • 10.

    Gong, S.; Qian, D.; Riazi, S.; et al. Association between the FRAIL Scale and Postoperative Complications in Older Surgical Patients: A Systematic Review and Meta-Analysis. Anesth. Analg. 2023, 136, 251–261. https://doi.org/10.1213/ANE.0000000000006272.

  • 11.

    Lai, J.; Covinsky, K.; Dodge, J.; et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology 2017, 66, 564–574. https://doi.org/10.1002/hep.29219.

  • 12.

    Lai, J.; Feng, S.; Terrault, N.; et al. Frailty predicts waitlist mortality in liver transplant candidates. Am. J. Transplant. 2014, 14, 1870–1879. https://doi.org/10.1111/ajt.12762.

  • 13.

    Klein, C.G.; Malamutmann, E.; Latuske, J.; et al. Frailty as a predictive factor for survival after liver transplantation, especially for patients with MELD ≤ 15—A prospective study. Langenbeck's Arch. Surg. 2021, 406, 1963–1969. https://doi.org/10.1007/s00423-021-02109-9.

  • 14.

    Ferriolli, E.; Roschel, H. Body Composition and Frailty: The Role of Adiposity. J. Nutr. Health Aging 2023, 27, 401–402. https://doi.org/10.1007/s12603-023-1930-0.

  • 15.

    Lai, J.; Tandon, P.; Bernal, W.; et al. Malnutrition, Frailty, and Sarcopenia in Patients with Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021, 74, 1611–1644. https://doi.org/10.1002/hep.32049. Corrected in Hepatology 2021, 74, 3563.

  • 16.

    Davies, B.; García, F.; Ara, I.; et al. Relationship Between Sarcopenia and Frailty in the Toledo Study of Healthy Aging: A Population Based Cross-Sectional Study. J. Am. Med. Dir. Assoc. 2018, 19, 282–286.

  • 17.

    Fumagalli, I.A.; Le, S.T.; Peng, P.D.; et al. Automated CT Analysis of Body Composition as a Frailty Biomarker in Abdominal Surgery. JAMA Surg. 2024, 159, 766–774. https://doi.org/10.1001/jamasurg.2024.0628.

  • 18.

    Reichelt, S.; Pratschke, J.; Engelmann, C.; et al. Body composition and the skeletal muscle compartment in liver transplantation: Turning challenges into opportunities. Am. J. Transplant. 2022, 22, 1943–1957. https://doi.org/10.1111/ajt.17089.

  • 19.

    Laube, R.; Wang, H.; Park, L.; et al. Frailty in advanced liver disease. Liver Int. 2018, 38, 2117–2128. https://doi.org/10.1111/liv.13917.

  • 20.

    Soysal, P.; Stubbs, B.; Lucato, P.; et al. Inflammation and frailty in the elderly: A systematic review and meta-analysis. Ageing Res. Rev. 2016, 31, 1–8. https://doi.org/10.1016/j.arr.2016.08.006. Erratum in Ageing Res. Rev. 2017, 35, 364–365.

  • 21.

    Yao, X.; Li, H.; Leng, S.X. Inflammation and immune system alterations in frailty. Clin. Geriatr. Med. 2011, 27, 79–87. https://doi.org/10.1016/j.cger.2010.08.002.

  • 22.

    Hubbard, R.; O’Mahony, M.; Savva, G.; et al. Inflammation and frailty measures in older people. J. Cell. Mol. Med. 2009, 13, 3103–3109. https://doi.org/10.1111/j.1582-4934.2009.00733.x.

  • 23.

    Collerton, J.; Martin-Ruiz, C.; Davies, K.; et al. Frailty and the role of inflammation, immunosenescence and cellular ageing in the very old: Cross-sectional findings from the Newcastle 85+ Study. Mech. Ageing Dev. 2012, 133, 456–466. https://doi.org/10.1016/j.mad.2012.05.005.

  • 24.

    Mehta, M.; Louissaint, J.; Parikh, N.S.; et al. Cognitive Function, Sarcopenia, and Inflammation Are Strongly Associated with Frailty: A Framingham Cohort Study. Am. J. Med. 2021, 134, 1530–1538. https://doi.org/10.1016/j.amjmed.2021.07.012.

  • 25.

    Ha, N.; Seetharaman, S.; Kent, D.; et al. Serum and plasma protein biomarkers associated with frailty in patients with cirrhosis. Liver Transpl. 2023, 29, 1089–1099. https://doi.org/10.1097/lvt.0000000000000128.

  • 26.

    Cardoso, C.; Matiollo, C.; Pereira, C.; et al. Patterns of dendritic cell and monocyte subsets are associated with disease severity and mortality in liver cirrhosis patients. Sci. Rep. 2021, 11, 5923. https://doi.org/10.1038/s41598-021-85148-y.

  • 27.

    Gadd, V.L.; Patel, P.J.; Jose, S.; et al. Altered Peripheral Blood Monocyte Phenotype and Function in Chronic Liver Disease: Implications for Hepatic Recruitment and Systemic Inflammation. PLoS ONE 2016, 11, e0157771. https://doi.org/10.1371/journal.pone.0157771.

Share this article:
How to Cite
Sattler, O.; Bosy-Westphal, A.; Elke, G.; Caliebe, A.; Peters, C.; Zitta, K. S.; Albrecht, M.; Braun, F.; Homayr, A. L. The FraiLtx Study Protocol: A Prospective, Single-Center Observational Study on Frailty, Systemic Inflammation, and Monocyte Subsets in Liver Transplant Candidates. Translational Insights 2026, 1 (1), 20. https://doi.org/10.53941/ti.2026.100020.
RIS
BibTex
Copyright & License
article copyright Image
Copyright (c) 2026 by the authors.
Article Metrics
26
Article Views
0
Citations