The Clinical Implications of Sex on Waitlist Outcomes in Patients With Acute-on-Chronic Liver Failure

Previous studies have examined the role of sex in the development and prognosis of acute-on-chronic liver failure (ACLF). To our knowledge, few studies have investigated sex-specific waitlist mortality rates stratified by ACLF grade. This question is significant, as women have historically faced greater barriers to liver transplantation and higher waitlist mortality rates compared to men with chronic liver disease. Therefore, understanding whether these disparities persist in ACLF-a condition with intermediate to high acuity-is essential for optimizing patient care and outcomes.

The study population was identified using United Network for Organ Sharing transplant data from 2005 to 2019 and included adult patients registered for liver transplantation. Candidates were stratified by ACLF grade at the time of waitlist registration and further stratified by sex. The primary outcomes were waitlist mortality and liver transplantation, analyzed using a competing-risk regression model to account for transplantation as a competing event. Secondary outcomes included cause-specific mortality, which was evaluated using cause-specific Cox proportional hazards models.

In the fully adjusted competing-risk regression model, male sex was associated with lower waitlist mortality among candidates without ACLF (subdistribution hazard ratio [SHR]: 0.87; 95% confidence interval [CI]: 0.83-0.90), ACLF grade 1 (SHR: 0.83; 95% CI: 0.73-0.95), and ACLF grade 2 (SHR: 0.81; 95% CI: 0.70-0.95), while no statistically significant difference was observed in ACLF grade 3 (SHR: 0.92; 95% CI: 0.80-1.06). Male sex was associated with higher liver transplantation rates across all ACLF strata.

Competing risk analysis demonstrated higher waitlist mortality among women than men in ACLF grades 1 and 2, potentially reflecting delayed transplant prioritization among female candidates.