Making an Equal System Equitable: Proposing a Sex-Adjusted MELDNa Score for Liver Transplantation Allocation

Background: Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on four laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex. We use data from electronic health records (EHRs) to describe sex differences in MELD labs and propose a sex adjustment. Methods: We extracted lab values for creatinine, International Normalized Ratio of prothrombin rate (INR), bilirubin, and sodium from EHRs at Vanderbilt University Medical Center (VUMC) and the All of Us Research Project to determine sex differences in lab traits. We calculated MELDNa scores within liver transplant recipients, non-transplanted liver disease cases, and non-liver disease controls separately. To account for sex differences in lab traits in MELDNa scoring, we created a sex-adjusted MELDNa map which outputs adjusted female scores mapped to male scores of equal liver disease severity. Using waitlist data from the Liver Simulated Allocation Modeling, we conducted simulations to determine if the sex-adjusted scores reduced sex disparities. Findings: In VUMC (n=623,931), all component MELDNa lab values yielded significant sex differences that disadvantage females in MELDNa scoring (creatinine: p<2.22x10 -308 ; bilirubin: p<2.22x10 -308 ; INR: p<2.22x10 -308 ; sodium: p<2.22x10 -308 ). This pattern persisted when the sample was divided into healthy controls, non-transplanted liver disease patients, and liver transplant patients, and in the All of Us cohort (n=56,715). Female transplant patients had a greater number of decompensation traits (p=0.005), despite having lower MELDNa scores (p=0.005), indicating MELDNa scores are not accurately representing disease severity in females. In simulations, the sex-adjusted MELDNa score modestly increased female transplantation rate and decreased overall death. Interpretation: Our results demonstrate pervasive sex differences in all labs used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol. Funding: The National Institutes of Health. Declaration of Interest: None to declare. Ethical Approval: This protocol was approved by the Vanderbilt University Medical Center institutional review board (#172020) and was deemed non-human subjects research because all information is de-identified.