TOPLINE

Bilirubin interference in the widely used Jaffe creatinine assay led to artificially elevated Model for End-Stage Liver Disease (MELD) scores in a substantial proportion of patients with end-stage liver disease (ESLD), and corrected scores reduced MELD scores in a substantial proportion of patients.

METHODOLOGY

• Researchers developed a correction model using 396 gravimetrically prepared creatinine-bilirubin concentration combinations analyzed with both Jaffe and enzymatic creatinine assays, validated against 32 patient samples measured by gas chromatography–isotope dilution mass spectrometry (GC-IDMS).
• The correction models were applied to 20,359 MELD calculations from 1375 patients with ESLD at a German tertiary care center.
• Investigators also evaluated 251,637 calculations from 20,444 liver transplant candidates in the US Scientific Registry of Transplant Recipients (SRTR) cohort who had creatinine measured using the Jaffe assay.
• The study was conducted retrospectively using data from May 2006 to April 2025 for the ESLD cohort and 1990 to 2022 for the SRTR cohort, with an additional contemporary subgroup analysis from 2023 to 2025.
• Patients in the ESLD cohort had median creatinine of 0.94 mg/dL and median total bilirubin of 1.10 mg/dL; SRTR patients had median creatinine of 1.16 mg/dL and median bilirubin of 3.4 mg/dL.
• Outcome included MELD score deviations following creatinine correction, 30-day and 90-day survival probabilities, restricted mean survival time, and transplant probability after creatinine correction.

TAKEAWAY

• The Jaffe assay overestimated creatinine by 7.19% compared with the reference standard, while the correction model reduced the proportional bias to 0.26%.
• After applying the correction model, clinically meaningful MELD score decreased by at least one point in 7.9%-12% of ESLD patients and 10.9%-13.8% of SRTR patients, depending on the MELD variant used.
• Deceased patients showed significantly higher odds of having score reductions compared to survivors (odds ratio, 1.3-2.3 in ESLD and 5.4-6.3 in SRTR).
• Among deceased ESLD patients, those with corrected reMELD-Na scores reduced by ≥1 point had significantly longer 90-day restricted mean survival times compared with those with unchanged scores (61.9 vs 38.2 days; hazard ratio [HR], 0.548; 95% CI, 0.395-0.760).
• In the SRTR cohort, patients with score reductions of ≥1 point showed lower transplantation probability across multiple MELD score classes (eg, MELD >25: subdistribution HR, 0.78; P = .0003), indicating clinically relevant differences in transplant access.

IN PRACTICE

These findings "underscore the critical need for methodological standardization in creatinine measurement to ensure fairness in liver transplant allocation," the authors wrote.

SOURCE

The study was led by Eda Kaya, Ruhr University Bochum in Bochum, Germany. It was published online on July 23 in Nature Communications.

LIMITATIONS

The experimental design did not completely isolate bilirubin interference from other method-specific sources of creatinine measurement variability. The correction formula was developed for a specific Jaffe assay and may not be applicable to all laboratories. Inter-laboratory variation in other MELD components such as international normalized ratio, bilirubin, or albumin was not assessed. It cannot be confirmed that all SRTR participating centers used identical Jaffe assay protocols.

DISCLOSURES

This study did not receive any specific funding. Two authors reported receiving research funding, and consulting fees from multiple pharmaceutical companies including Intercept, Aligos, Akero, Abbott, Cymabay, Boehringer Ingelheim, and GSK.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.