Clinical burden of physical frailty in patients evaluated for liver transplantation: A retrospective cohort study

doi:10.4254/wjh.v18.i3.114279

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Mar 27, 2026 (publication date) through Mar 26, 2026

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World Journal of Hepatology

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Cohort Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Hepatol. Mar 27, 2026; 18(3): 114279
Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.114279

Clinical burden of physical frailty in patients evaluated for liver transplantation: A retrospective cohort study

Heidi E Johnston, Hannah E Mayr, Melita E Andelkovic, Tahnie G Takefala, Yanyan Chen, Aaron P Thrift, Ingrid J Hickman, Graeme A Macdonald

Heidi E Johnston, Hannah E Mayr, Tahnie G Takefala, Ingrid J Hickman, Nutrition and Dietetics, Princess Alexandra Hospital, Brisbane 4102, Queensland, Australia

Heidi E Johnston, Hannah E Mayr, Melita E Andelkovic, Ingrid J Hickman, Graeme A Macdonald, Faculty of Medicine, The University of Queensland, Brisbane 4067, Queensland, Australia

Heidi E Johnston, Melita E Andelkovic, Tahnie G Takefala, Graeme A Macdonald, Queensland Liver Transplant Service, Princess Alexandra Hospital, Brisbane 4102, Queensland, Australia

Hannah E Mayr, Centre for Functioning and Health Research, Metro South Health, Brisbane 4102, Queensland, Australia

Melita E Andelkovic, Graeme A Macdonald, Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane 4102, Queensland, Australia

Yanyan Chen, Aaron P Thrift, Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX 77001, United States

Aaron P Thrift, Dan L Duncan Comprehensive Cancer Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77001, United States

Ingrid J Hickman, ULTRA Team, The University of Queensland Clinical Trial Capability, The University of Queensland, Brisbane 4067, Queensland, Australia

Author contributions: Johnston HE, Mayr HE, Hickman IJ, and Macdonald GA were responsible for study concept and design, drafting of the manuscript, and administrative/technical or material support; Johnston HE, Andelkovic ME, and Takefala TG collected the data; Johnston HE, Mayr HE, Chen Y, Thrift AP, Hickman IJ, and Macdonald GA performed data analysis and interpretation as well as statistical analysis; Johnston HE, Mayr HE, Andelkovic ME, Takefala TG, Chen Y, Thrift AP, Hickman IJ, and Macdonald GA critically revised the manuscript for important intellectual content; Johnston HE obtained funding; and all authors have read and approved the final manuscript.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Metro South Health, approval No. HREC/2018/QMS/46728.

Informed consent statement: The informed consent was waived by the Institutional Review Board.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: The datasets generated and analysed during the current study are not publicly available because they contain sensitive patient information. De-identified data may be made available from the corresponding author on reasonable request (heidi.johnston@health.qld.gov.au), subject to approval of an institutional data-sharing agreement.

Corresponding author: Heidi E Johnston, PhD, Nutrition and Dietetics, Princess Alexandra Hospital, 199 Ipswich Road, Woolloongabba QLD 4102, Brisbane 4102, Queensland, Australia. heidi.johnston@health.qld.gov.au

Received: September 16, 2025
Revised: December 17, 2025
Accepted: January 22, 2026
Published online: March 27, 2026
Processing time: 191 Days and 23.6 Hours

Abstract

BACKGROUND

Frailty has been associated with mortality among patients referred for liver transplantation (LT), yet the impact on other clinical outcomes is less well defined.

AIM

To investigate the effect of physical frailty, measured by the liver frailty index (LFI), on the likelihood of LT, pre- and early post-LT outcomes, in an Australian cohort.

METHODS

Data were collected on adults with cirrhosis referred for LT and had their baseline LFI assessment. Outcomes of interest included: Receiving a LT, pre-LT unplanned hospitalizations, LT surgical complications, intensive care unit (ICU) and hospital length of stay. Cox proportional hazards modelling determined associations between LFI and outcomes, adjusting for age, sex, hepatocellular carcinoma, and model for end-stage liver disease score. Competing risk analysis explored reasons for not being transplanted including waitlist mortality [sub-hazards ratio (HR)].

RESULTS

Among 266 patients [median model for end-stage liver disease 16 (interquartile range 11-19)], the median LFI was 3.7 (3.3-4.1); 19% were robust, 68% pre-frail, and 14% frail. After adjustment, each 1-point increase in the LFI was associated with a 29% lower likelihood of receiving a LT [HR = 0.71, 95% confidence interval (CI): 0.54-0.94, P = 0.020]. Competing-risk analysis showed higher LFI increased waitlist mortality (sub-HR = 1.90, 95%CI: 1.33-2.70). Each 1-point rise also conferred a 69% higher risk of unplanned pre-LT hospitalization (HR = 1.69, 95%CI: 1.09-2.62, P = 0.020). Among transplanted patients, higher LFI predicted prolonged ICU stay (> 4 days; odds ratio = 3.24, 95%CI: 1.06-9.85). Frailty was not associated with surgical complications or hospital length of stay.

CONCLUSION

Physical frailty independently predicts reduced LT likelihood, higher waitlist mortality, greater pre-LT unplanned hospitalizations, and prolonged ICU stay. This study provides the first Australian validation, extending LFI evidence beyond United States cohorts.

Keywords: Liver frailty index; Cirrhosis; Unplanned hospitalizations; Waitlist mortality; Length of stay

Core Tip: Frailty is increasingly recognized as a predictor of adverse outcomes in liver transplantation (LT), yet evidence using the liver frailty index (LFI) outside the United States is limited. This study is the first to evaluate the LFI in an Australian LT cohort, demonstrating its ability to identify patients at higher risk of waitlist mortality, unplanned hospitalizations, and prolonged intensive care unit stay after LT. These findings validate the LFI as a valuable tool for risk stratification, supporting its integration into LT assessment to guide surveillance and resource allocation for interventions.