MELD Scoring for Liver Transplants in Need of Sex Adjustment, Study Says

Laboratory traits used in the calculation of sodium-adjusted model for end-stage liver disease (MELDNa) scores placed women at a distinct disadvantage, researchers reported.

In an electronic health record (EHR)-based study of more than 600,000 participants, all calculated laboratory values that make up the scoring system showed significant and “pervasive sex differences” between women and men, respectively (P<0.001 for all):

• Mean creatinine: 0.79 vs 0.99 mg/dL
• Bilirubin: 0.58 vs 0.76 mg/dL
• International normalized ratio of prothrombin rate: 1.20 vs 1.24
• Sodium: 139.03 vs 139.00 mEq/L

And the pattern persisted regardless of whether patients were undergoing a liver transplant, had liver disease without undergoing transplant, or were healthy, according to Lea Davis, PhD, of the Vanderbilt Genetics Institute in Nashville, Tennessee, and colleagues, writing in JAMA Surgery.

Women who underwent liver transplants had more decompensation traits (mean 1.60 vs 1.34), even though they had lower MELDNa scores before transplantation (mean 20.21 vs 21.72, P=0.005 for both).

“All laboratory traits used in the calculation of MELDNa scores show sex differences that increase male individuals’ scores compared with female individuals’, despite female individuals showing greater liver decompensation,” the group concluded.

In a proposed, sex-adjusted MELDNa scoring allocation model, slightly more women would have received a liver transplant than men (24.1% vs 23.1%); under the Organ Procurement and Transplantation Network (OPTN) MELDNa scoring, more men received transplants (23.7% vs 23.0%).

The simulated sex-adjusted model also showed a moderate reduction in deaths at 1 year compared to the OPTN model (2,480 vs 2,493), which “suggested that the sex-adjusted scores could help save lives,” the researchers noted.

“This may provide a meaningful path forward toward mitigating sex-based disparities in liver transplant,” stated Jayme Locke, MD, MPH, and Brittany Shelton, MPH, both of the University of Alabama at Birmingham, in an accompanying editorial.

However, they cautioned that the “authors derived these conclusions through use of liver simulated allocation modeling, a discrete event simulation that does not incorporate candidate size. Existing literature suggests much of the disparity in transplant rates can be attributed to differences in candidate size and as such, the findings from this article may be slightly overestimated owing to the inability to account for this.”

The authors did acknowledge that current liver simulated allocation modeling (LSAM) “accept/decline models do not take into account height, leading to a underestimation of the sex disparity in transplant rates.”

The MELD score was first adopted by the OPTN in 2002, prior to the addition of sodium, Davis’ group noted. But many argue that the score does not accurately reflect disease severity. Female transplant patients are more likely to be delisted from waiting lists for being “too sick” and have an increased risk of death while awaiting transplantation, they added.

“Previous studies ascribed sex differences in MELDNa scores to known sex differences in creatinine levels, but creatinine does not fully account for the sex difference in MELDNa scores,” wrote Davis and colleagues.

For their study, the researchers examined EHR data on 623,931 individuals who received care at the Vanderbilt University Medical Center (VUMC) from March 2019 to April 2020. Replication analyses were performed at the multisite NIH All of Us Research Program.

Most of the participants were healthy controls (n=598,409), while 601 were liver transplant patients and 24,921 had chronic liver disease but did not undergo transplant. Across the entire cohort, the median age was 44 years and 57.7% were women. Individuals with liver cancer or on dialysis were excluded.

Study limitations included the fact that listing and delisting dates were unavailable. Also, because lab tests were not uniformly ordered, diagnostic bias could have affected the sample. Finally, the effects of the MELDNa score on race or genetic ancestry were not assessed.