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. 2021 Mar 1;156(3):256-262.
doi: 10.1001/jamasurg.2020.5674.

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

Jennifer C Lai  1 , Daniel R Ganger  2 , Michael L Volk  3   4 , Jennifer L Dodge  1 , Michael A Dunn  5   6 , Andres Duarte-Rojo  5   6 , Matthew R Kappus  7 , Robert S Rahimi  8 , Daniela P Ladner  9   10 , Brian Boyarsky  11 , Mara McAdams-DeMarco  12 , Dorry L Segev  11 , Charles E McCulloch  13 , Elizabeth C Verna  14
Affiliations

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

Jennifer C Lai et al. JAMA Surg. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Lai reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study and personal fees from Axcella Health, Inc, BioMarin Pharmaceutical, Inc, Ambys Medicines, Inc, and Third Rock Ventures and grants from Pliant Therapeutics, Inc, outside the submitted work. Dr Ganger reported receiving grants from the University of California, San Francisco, during the conduct of the study and personal fees from Gilead Sciences, Inc, and Mallinckrodt Pharmaceuticals outside the submitted work. Dr Duarte-Rojo reported receiving personal fees from Axcella Health, Inc, and Mallinckrodt Pharmaceuticals outside the submitted work. Dr Ladner reported receiving grants from Northwestern University during the conduct of the study. Dr McAdams-DeMarco reported receiving grants from the National Institute of Aging during the conduct of the study. Dr McCulloch reported receiving grants from the NIH during the conduct of the study. Dr Verna reported receiving grants from Salix Pharmaceuticals, Inc, and personal fees from Gilead Sciences, Inc, outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Functional Assessment in Liver Transplantation Study Participant Enrollment
DDLT indicates deceased donor liver transplant; HCC, hepatocellular carcinoma; MELDNa, laboratory-based Model for End-stage Liver Disease incorporating sodium level.
Figure 2.
Figure 2.. Cumulative Incidence of Wait List Mortality by Sex
See this image and copyright information in PMC

Comment in

References

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