Sex-Adjusted Liver Allocation Scoring Tool Would Improve Transplant Equity

By Patricia A. Sheiner MD

June 01, 2022

NEW YORK (Reuters Health) - Females on the liver transplant waiting list are disadvantaged by the sodium-adjusted Model for End-stage Liver Disease score (MELDNa) currently employed to guide allocation decisions, but a sex-adjusted MELDNa score would help address the inequity and decrease mortality for both sexes, researchers say.

Dr. Julia Sealock of Vanderbilt University Medical Center in Nashville, Tennessee and colleagues developed a sex-adjusted score after first analyzing their institution's health records on 623,931 individuals (58% female), including 601 liver transplant patients, 24,915 patients with liver disease who did not undergo transplant, and 598,409 healthy controls.

Across all individuals, calculated Meld NA scores were higher among males vs females (mean scores: 11.09 vs 9.78, respectively; P<0.001), they reported in JAMA Surgery. All component Meld NA lab values differed significantly in males vs females, respectively, with mean creatinine 0.99 vs 0.79 mg/dL (P<0.001); mean bilirubin 0.76 vs 0.58 mg/dL (P<0.001); international normalized ratio (INR) of prothrombin rate 1.24 vs 1.20 (P<0.001); and sodium 139.00 vs 139.03 mEq/L (P< 0.001).

Among healthy controls, total MELDNa was higher in males than in females (10.80 vs 9.54; P<0.001). While sodium levels were similar in males and females (139.06 vs 139.06 mEq/L, respectively; P=.60), the males had higher mean creatinine (0.99 vs 0.79 mg/dL; P<0.001), INR (1.24 vs 1.19; P<0.001) and bilirubin levels (0.73 vs 0.56; P<0.001).

Among liver transplant recipients, males had higher mean pretransplant creatinine levels (1.26 vs 1.11 mg/dL; P=0.001) but similar pretransplant INR (1.78 vs 1.80; P=0.74), bilirubin (4.00 vs 4.27 mg/dL; P=0.26), and sodium (134.46 vs 134.80 mEq/L; P=0.36). Pretransplant total MELD Na scores were significantly higher in males (21.72 vs 20.21; P=.005). But the mean number of liver decompensation markers such as hematemesis, gastrointestinal hemorrhage, ascites, jaundice and hepatic encephalopathy were higher in women (1.60) than in men (1.34; P=0.005), suggesting that females have more decompensation before undergoing transplant and that MELDNa scores are not accurately representing their disease severity.

Among patients with at least two components of chronic liver disease who had not received a liver transplant, males had higher mean levels of creatinine (1.02 vs 0.83 mg/dL; P<0.001), INR (1.24 vs 1.20; P<0.001), and bilirubin (0.99 vs 0.78 mg/dL; P<0.001), and lower sodium levels (138.34 vs 138.65 mEq/L; P<0.001) compared with female. Total MELDNa scores were also significantly higher in males with liver disease (12.01 vs 10.68; P<0.001).

In a validation cohort of patients in the All of US database, although only 25 patients had undergone liver transplant, similar differences were seen in MELDNa across groups.

Currently in the United States, using MELDNa, men receive a liver transplant at a 0.7% higher rate than women, the researchers say. When they used a liver simulated allocation model (LSAM) to test a sex adjusted MELDNa tool incorporating decompensation traits, whereby females received a mean increase of 1.6 (0-2) points, they found that females would receive a transplant at a 1% higher rate than males but total death counts would drop for both sexes. Waiting list mortality would decrease among females and remain unchanged for males.

In an editorial, Brittany Shelton and Dr. Jayme Locke from the University of Alabama acknowledge that women are less likely to receive a liver transplant and more likely die on the waiting list. They agree that more objective measurements of disease severity are necessary but add 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. Nevertheless, this may provide a meaningful path forward toward mitigating sex-based disparities in liver transplant."

SOURCE: and JAMA Surgery, online May 18, 2022.