Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2020 Sep;73(3):575-581.
doi: 10.1016/j.jhep.2020.03.029. Epub 2020 Mar 30.

Changes in frailty are associated with waitlist mortality in patients with cirrhosis

Jennifer C Lai  1 , Jennifer L Dodge  2 , Matthew R Kappus  3 , Michael A Dunn  4 , Michael L Volk  5 , Andres Duarte-Rojo  6 , Daniel R Ganger  7 , Robert S Rahimi  8 , Charles E McCulloch  9 , Christine E Haugen  10 , Mara McAdams-DeMarco  11 , Daniela P Ladner  12 , Dorry L Segev  10 , Elizabeth C Verna  13 ; Multi-Center Functional Assessment in Liver Transplantation (FrAILT) Study
Affiliations
Multicenter Study

Changes in frailty are associated with waitlist mortality in patients with cirrhosis

Jennifer C Lai et al. J Hepatol. 2020 Sep.

Abstract

Background & aims: To date, studies evaluating the association between frailty and mortality in patients with cirrhosis have been limited to assessments of frailty at a single time point. We aimed to evaluate changes in frailty over time and their association with death/delisting in patients too sick for liver transplantation.

Methods: Adults with cirrhosis, listed for liver transplantation at 8 US centers, underwent ambulatory longitudinal frailty testing using the liver frailty index (LFI). We used multilevel linear mixed-effects regression to model and predict changes in LFI (ΔLFI) per 3 months, based on age, gender, model for end-stage liver disease (MELD)-Na, ascites, and hepatic encephalopathy, categorizing patients by frailty trajectories. Competing risk regression evaluated the subhazard ratio (sHR) of baseline LFI and predicted ΔLFI on death/delisting, with transplantation as the competing risk.

Results: We analyzed 2,851 visits from 1,093 outpatients with cirrhosis. Patients with severe worsening of frailty had worse baseline LFI and were more likely to have non-alcoholic fatty liver disease, diabetes, or dialysis-dependence. After a median follow-up of 11 months, 223 (20%) of the overall cohort died/were delisted because of sickness. The cumulative incidence of death/delisting increased by worsening ΔLFI group. In competing risk regression adjusted for baseline LFI, age, height, MELD-Na, and albumin, a 0.1 unit change in ΔLFI per 3 months was associated with a 2.04-fold increased risk of death/delisting (95% CI 1.35-3.09).

Conclusion: Worsening frailty was significantly associated with death/delisting independent of baseline frailty and MELD-Na. Notably, patients who experienced improvements in frailty had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty, using the LFI, in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Lay summary: Frailty, as measured at a single time point, is predictive of death in patients with cirrhosis, but whether changes in frailty over time are associated with death is unknown. In a study of over 1,000 patients with cirrhosis who underwent frailty testing, we demonstrate that worsening frailty is strongly linked with mortality, regardless of baseline frailty and liver disease severity. Notably, patients who experienced improvements in frailty over time had a lower risk of death/delisting. Our data support the longitudinal measurement of frailty in patients with cirrhosis and lay the foundation for interventional work aimed at reversing frailty.

Keywords: Malnutrition; Physical function; Portal hypertension; Quality of life.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Figure 1.
Figure 1.
Flow chart of the study population. (Abbreviations: DDLT, deceased donor liver transplantation; MELD, Model for End-Stage Liver Disease)
Figure 2.
Figure 2.
Change in the Liver Frailty Index scores per 3 months by ΔLFI trajectory group (medians and interquartile ranges).
Figure 3.
Figure 3.
Observed cumulative incidence of waitlist mortality by categories of ΔLFI per 3 months.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology 2017;66:564–74. doi:10.1002/hep.29219. - DOI - PMC - PubMed
    1. Lai JC, Rahimi RS, Verna EC, Kappus MR, Dunn MA, McAdams-DeMarco M, et al. Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study. Gastroenterology 2019. doi:10.1053/j.gastro.2019.01.028. - DOI - PMC - PubMed
    1. Haugen CE, McAdams-DeMarco M, Holscher CM, Ying H, Gurakar AO, Garonzik-Wang J, et al. Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates. Ann Surg 2019:1–5. doi:10.1097/SLA.0000000000003207. - DOI - PMC - PubMed
    1. Haugen CE, McAdams-DeMarco MA, Verna EC, Rahimi RS, Kappus MR, Dunn MA, et al. Body mass index, frailty, and waitlist mortality: From the Multi-center Functional Assessment in Liver Transplantation (FrAILT) Study. JAMA Surg n.d.
    1. Gill TM, Murphy TE, Gahbauer EA, Allore HG. The Course of Disability Before and After a Serious Fall Injury. JAMA Intern Med 2013;173:1780–6. doi:10.1001/jamainternmed.2013.9063. - DOI - PMC - PubMed

Publication types