Dataset Information

Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation.

ABSTRACT:

Importance

Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.

Objective

To use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a sex adjustment.

Design, setting, and participants

A retrospective cohort study was conducted from March 2019 to April 2020 to evaluate sex differences in laboratory values in liver transplant patients, patients with liver disease who did not undergo transplant, and healthy controls. Primary analyses were conducted in Vanderbilt University Medical Center (VUMC)'s deidentified electronic health record system. Replication analyses were conducted in the All of Us Research Program. Simulations of a sex-adjusted sodium-adjusted MELD (MELDNa) score were completed using liver transplant waiting list data from the liver simulated allocation modeling system. Patients who regularly used VUMC with measurements for any MELDNa component laboratory were included in the analyses. Analysis took place from November 2019 to March 2021.

Exposures

Electronic health record-reported sex.

Main outcomes and measure

Creatinine, bilirubin, international normalized ratio, and sodium levels.

Results

The VUMC sample was composed of 623 931 individuals (359 976 [57.7%] female) with a median (IQR) age of 44 (23-61) years. All component MELDNa laboratory values and calculated MELDNa scores yielded significant sex differences within VUMC (mean [SD] creatinine: male, 0.99 [0.39] mg/dL; female, 0.79 [0.30] mg/dL; P < .001; bilirubin: male, 0.76 [0.83] mg/dL; female, 0.58 [0.64] mg/dL; P < .001; international normalized ratio of prothrombin rate: male, 1.24 [0.42]; female, 1.20 [0.40]; P < .001; sodium: male, 139.00 [2.36] mEq/L; female, 139.03 [2.28] mEq/L; P < .001), resulting in MELDNa scoring that disadvantaged female individuals. This pattern persisted when the sample was divided into healthy controls, individuals with liver disease who did not undergo transplant, and patients who did undergo liver transplant. Female transplant patients had a greater number of decompensation traits (mean [SD]: male, 1.34 [1.11]; female, 1.60 [1.09]; P = .005), despite having lower MELDNa scores (mean [SD]: male, 21.72 [6.11]; female, 20.21 [6.15]; P = .005), indicating MELDNa scores are not accurately representing disease severity in female individuals. In simulations, the sex-adjusted MELDNa score modestly increased female transplant rate and decreased overall death.

Conclusions and relevance

These results demonstrate pervasive sex differences in all laboratory values used in MELDNa scoring and highlight the need and utility of a sex-adjustment to the MELDNa protocol.

SUBMITTER: Sealock JM

PROVIDER: S-EPMC9118088 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation.

Sealock Julia M JM Ziogas Ioannis A IA Zhao Zhiguo Z Ye Fei F Alexopoulos Sophoclis P SP Matsuoka Lea L Chen Guanhua G Davis Lea K LK

JAMA surgery 20220701 7

<h4>Importance</h4>Liver allocation is determined by the model for end-stage liver disease (MELD), a scoring system based on 4 laboratory measurements. During the MELD era, sex disparities in liver transplant have increased and there are no modifications to MELD based on sex.<h4>Objective</h4>To use laboratory values stored in electronic health records to describe population-level sex differences in all MELD laboratory values (in healthy individuals and patients with liver disease) and propose a ...[more]

PMID: 35583884

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Project description:IntroductionDonation after circulatory death (DCD) liver transplantation (LT) makes up well less than 1% of all LTs with a Model for End-Stage Liver Disease (MELD)≥35 in the United States. We hypothesized DCD-LT yields acceptable ischemia-reperfusion and reasonable outcomes for recipients with MELD≥35.MethodsWe analyzed recipients with lab-MELD≥35 at transplant within the UCSF (n=41) and the UNOS (n=375) cohorts using multivariate Cox regression and propensity score matching.ResultsIn the UCSF cohort, five-year patient survival was 85% for DCD-LTs and 86% for matched-Donation after Brain Death donors-(DBD) LTs (p=0.843). Multivariate analyses showed that younger donor/recipient age and more recent transplants (2011-2021 versus 1999-2010) were associated with better survival. DCD vs. DBD graft use did not significantly impact survival (HR: 1.2, 95%CI 0.6-2.7). The transaminase peak was approximately doubled, indicating suggesting an increased ischemia-reperfusion hit. DCD-LTs had a median post-LT length of stay of 11 days, and 34% (14/41) were on dialysis at discharge versus 12 days and 22% (9/41) for DBD-LTs. 27% (11/41) DCD-LTs versus 12% (5/41) DBD-LTs developed a biliary complication (p=0.095). UNOS cohort analysis confirmed patient survival predictors, but DCD graft emerged as a risk factor (HR: 1.5, 95%CI 1.3-1.9) with five-year patient survival of 65% versus 75% for DBD-LTs (p=0.016). This difference became non-significant in a sub-analysis focusing on MELD 35-36 recipients. Analysis of MELD≥35 DCD recipients showed that donor age of <30yo independently reduced the risk of graft loss by 30% (HR, 95%CI: 0.7 (0.9-0.5), p=0.019). Retransplant status was associated with a doubled risk of adverse event (HR, 95%CI: 2.1 (1.4-3.3), p=0.001). The rejection rates at 1y were similar between DCD- and DBD-LTs, (9.3% (35/375) versus 1,541 (8.7% (1,541/17,677), respectively).DiscussionIn highly selected recipient/donor pair, DCD transplantation is feasible and can achieve comparable survival to DBD transplantation. Biliary complications occurred at the expected rates. In the absence of selection, DCD-LTs outcomes remain worse than those of DBD-LTs.

Project description:BackgroundControversy exists regarding the best predictive model of liver transplant waiting list (WL) mortality. Models for end-stage liver disease-glomerular filtration rate assessment in liver disease (MELD-GRAIL) and MELD-GRAIL-Na were recently described to provide better prognostication, particularly in females. We evaluated the performance of these scores compared to MELD and MELD-Na.MethodsConsecutive patients with cirrhosis waitlisted for liver transplant from 1998 to 2017 were examined in this single-center study. The primary outcome was 90-d WL mortality. MELD, MELD-Na, MELD-GRAIL, and MELD-GRAIL-Na at the time of WL registration were compared. Model discrimination was assessed with area under the receiver operating characteristic curves and Harrell's C-index after fitting Cox models. Model calibration was examined with Grønnesby and Borgan's modification of the Hosmer-Lemeshow formula and by comparing predicted/observed outcomes across model strata.ResultsThe study population comprised 1108 patients with a median age of 53.5 (interquartile range 48-59) y and male predominance (74.9%). All models had excellent areas under the receiver operating characteristic curves for the primary outcome (MELD 0.89, MELD-Na 0.91, MELD-GRAIL 0.89, MELD-GRAIL-Na 0.89; all comparisons P > 0.05). Youden index cutoffs for 90-d mortality were as follows: MELD, 19; MELD-Na, 22; MELD-GRAIL, 18; and MELD-GRAIL-Na, 17. Variables associated with 90-d mortality on multivariable Cox regression were sodium, bilirubin, creatinine, and international normalized ratio. There were no differences in model discrimination using Harrell's C-index. All models were well calibrated; however, divergence between observed and predicted mortality was noted with scores ≥25.ConclusionThere were no demonstrable differences in discrimination or calibration of GRAIL-based models compared with MELD or MELD-Na in our cohort. This suggests that GRAIL-based models may not have meaningful improvements in discriminatory ability when applied to other settings.

Dataset Information

Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation.

Importance

Objective

Design, setting, and participants

Exposures

Main outcomes and measure

Results

Conclusions and relevance

Publications

Proposing a Sex-Adjusted Sodium-Adjusted MELD Score for Liver Transplant Allocation.

Similar Datasets

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