Highlights
- •In patients with cirrhosis, changes in frailty were significantly associated with death/delisting.
- •Patients with cirrhosis 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.
- •This study lays the foundation for interventional work aimed at reversing frailty.
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.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 30, 2020
Accepted:
March 19,
2020
Received in revised form:
March 10,
2020
Received:
November 14,
2019
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
