Frailty Likely Contributes to Gender Gap in Liver Transplant Wait-List Mortality

By Marilynn Larkin

January 06, 2021

NEW YORK (Reuters Health) - Among liver transplant candidates without cancer, frailty is associated with the gender gap in wait-list mortality, researchers suggest.

"The liver transplant community has known for over a decade that women experience worse outcomes than men on the liver transplant wait list. Women awaiting liver transplantation are less likely to get a liver transplant and more likely to die than men," Dr. Jennifer Lai of the University of California, San Francisco told Reuters Health by email. The gap has persisted, she said, despite numerous studies, with no findings that were "immediately actionable."

That said, she added, "Frailty is potentially modifiable through interventions that focus on nutritional intake and exercise, so we can use this information to empower and motivate women awaiting liver transplantation to focus on these health factors."

As reported in JAMA Surgery, Dr. Lai and colleagues studied 1,405 patients (41% women; median age, 58) with cirrhosis (and without liver cancer) awaiting liver transplant at nine U.S. centers from 2012-2019. The Liver Frailty Index (LFI) score, incorporating grip strength, chair stands, and balance, was calculated for each participant at baseline. Median follow-up time was 10.6 months for women and 10.2 months for men.

Women and men had the same median score - 18 - on the Model for End-stage Liver Disease incorporating sodium levels (MELDNa), but the baseline LFI was higher in women (mean, 4.12 vs. 4.00). More women were unable to balance for 30 seconds (25% vs. 18%); women also had worse sex-adjusted grip strength and fewer chair stands per second.

After adjustment for other variables associated with frailty, LFI was 0.16 units higher in women than men. In unadjusted regression analysis, women had a 34% increased risk of wait list mortality compared to men.

Further covariables adjustment did not alter the association between sex and wait list mortality; however, adjustment for LFI attenuated the mortality gap between women and men, mediating 13% of the gap.

Summing up, the authors state, "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."

Dr. Lai said, "Based on these results, we advocate for systematic assessment of frailty with an objective tool, such as the LFI, in all patients with cirrhosis awaiting liver transplantation." While societies such as the American Society of Transplantation include a frailty assessment for all transplant patients, she said, "actual implementation has been slow to date. Our study adds additional data that should motivate transplant centers to implement such assessments."

Dr. Jayme Locke of the University of Alabama at Birmingham Comprehensive Transplant Institute, coauthor of a related editorial, told Reuters Health by email, "MELD-based allocation, introduced in 2002, inadvertently widened the existing gender disparity gap in access to a life-saving therapy and nearly a decade later, we still have not rectified the injustice. Despite our best efforts we have never been able to get traction with regard to revising MELD such that it accurately reflects disease severity independent of gender."

"The LFI is an objective, reproducible tool that can be incorporated into the allocation system to account for the disease severity in women not reflected in their MELD score," he said. "It is time for the National Liver Review Board and Organ Procurement and Transplantation Network to respond to the call for a more equitable process of distributing this live-saving therapy."

SOURCE: and JAMA Surgery, online December 30, 2020.