Dataset Information

Association of Frailty and Sex With Wait List Mortality in Liver Transplant Candidates in the Multicenter Functional Assessment in Liver Transplantation (FrAILT) Study.

ABSTRACT:

Importance

Female liver transplant candidates experience higher rates of wait list mortality than male candidates. Frailty is a critical determinant of mortality in patients with cirrhosis, but how frailty differs between women and men is unknown.

Objective

To determine whether frailty is associated with the gap between women and men in mortality among patients with cirrhosis awaiting liver transplantation.

Design, setting, and participants

This prospective cohort study enrolled 1405 adults with cirrhosis awaiting liver transplant without hepatocellular carcinoma seen during 3436 ambulatory clinic visits at 9 US liver transplant centers. Data were collected from January 1, 2012, to October 1, 2019, and analyzed from August 30, 2019, to October 30, 2020.

Exposures

At outpatient evaluation, the Liver Frailty Index (LFI) score was calculated (grip strength, chair stands, and balance).

Main outcomes and measures

The risk of wait list mortality was quantified using Cox proportional hazards regression by frailty. Mediation analysis was used to quantify the contribution of frailty to the gap in wait list mortality between women and men.

Results

Of 1405 participants, 578 (41%) were women and 827 (59%) were men (median age, 58 [interquartile range (IQR), 50-63] years). Women and men had similar median scores on the laboratory-based Model for End-stage Liver Disease incorporating sodium levels (MELDNa) (women, 18 [IQR, 14-23]; men, 18 [IQR, 15-22]), but baseline LFI was higher in women (mean [SD], 4.12 [0.85] vs 4.00 [0.82]; P = .005). Women displayed worse balance of less than 30 seconds (145 [25%] vs 149 [18%]; P = .003), worse sex-adjusted grip (mean [SD], -0.31 [1.08] vs -0.16 [1.08] kg; P = .01), and fewer chair stands per second (median, 0.35 [IQR, 0.23-0.46] vs 0.37 [IQR, 0.25-0.49]; P = .04). In unadjusted mixed-effects models, LFI was 0.15 (95% CI, 0.06-0.23) units higher in women than men (P = .001). After adjustment for other variables associated with frailty, LFI was 0.16 (95% CI, 0.08-0.23) units higher in women than men (P < .001). In unadjusted regression, women experienced a 34% (95% CI, 3%-74%) increased risk of wait list mortality than men (P = .03). Sequential covariable adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men. In mediation analysis, an estimated 13.0% (IQR, 0.5%-132.0%) of the gender gap in wait list mortality was mediated by frailty.

Conclusions and relevance

These findings demonstrate that women with cirrhosis display worse frailty scores than men despite similar MELDNa scores. The higher risk of wait list mortality that women experienced appeared to be explained in part by frailty.

SUBMITTER: Lai JC

PROVIDER: S-EPMC7774043 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundUnderstanding how frailty affects patients listed for transplantation has been identified as a priority research need. Frailty may be associated with a high risk of death or wait-list withdrawal, but this has not been evaluated in a large multicenter cohort of Canadian wait-listed patients.ObjectiveThe primary objective is to evaluate whether frailty is associated with death or permanent withdrawal from the transplant wait list. Secondary objectives include assessing whether frailty is associated with hospitalization, quality of life, and the probability of being accepted to the wait list.DesignProspective cohort study.SettingSeven sites with established renal transplant programs that evaluate patients for the kidney transplant wait list.PatientsIndividuals who are being considered for the kidney transplant wait list.MeasurementsWe will assess frailty using the Fried Phenotype, a frailty index, the Short Physical Performance Battery, and the Clinical Frailty Scale at the time of listing for transplantation. We will also assess frailty at the time of referral to the wait list and annually after listing in a subgroup of patients.MethodsThe primary outcome of the composite of time to death or permanent wait-list withdrawal will be compared between patients who are frail and those who are not frail and will account for the competing risks of deceased and live donor transplantation. Secondary outcomes will include number of hospitalizations and length of stay, and in a subset, changes in frailty severity over time, change in quality of life, and the probability of being listed. Recruitment of 1165 patients will provide >80% power to identify a relative hazard of ≥1.7 comparing patients who are frail to those who are not frail for the primary outcome (2-sided α = .05), whereas a more conservative recruitment target of 624 patients will provide >80% power to identify a relative hazard of ≥2.0.ResultsThrough December 2019, 665 assessments of frailty (inclusive of those for the primary outcome and all secondary outcomes including repeated measures) have been completed.LimitationsThere may be variation across sites in the processes of referral and listing for transplantation that will require consideration in the analysis and results.ConclusionsThis study will provide a detailed understanding of the association between frailty and outcomes for wait-listed patients. Understanding this association is necessary before routinely measuring frailty as part of the wait-list eligibility assessment and prior to ascertaining the need for interventions that may modify frailty.Trial registrationNot applicable as this is a protocol for a prospective observational study.

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