Multicenter validation of the liver graft assessment following transplantation (L-GrAFT) score for assessment of early allograft dysfunction.

Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. Previously we reported that the liver graft assessment following transplantation (L-GrAFT 7) risk score was superior to binary EAD or the model for early allograft function (MEAF) score for estimating 3-month graft failure-free survival in a single-center derivation cohort. Herein, we sought to externally validate L-GrAFT 7 , and compare its prognostic performance to EAD and MEAF. Accuracies of L-GrAFT 7 , EAD, and MEAF were compared in a 3-center US validation cohort (n = 3,201), and a Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion (NMP) trial cohort (n = 222); characteristics were compared to assess generalizability. Compared to the derivation cohort, patients in the validation and NMP trial cohort had lower recipient median MELD scores; were less likely to require pretransplant hospitalization, renal replacement therapy or mechanical ventilation; and had superior 1-year overall (90% and 95% vs. 84%) and graft failure-free (88% and 93% vs. 81%) survival, with a lower incidence of 3-month graft failure (7.4% and 4.0% vs. 11.1%; p < 0.001 for all comparisons). Despite significant differences in cohort characteristics, L-GrAFT 7 maintained an excellent validation AUROC of 0.78, significantly superior to binary EAD (AUROC 0.68, p = 0.001) and MEAF scores (AUROC 0.72, p < 0.001). In post hoc analysis of the COPE NMP trial, the highest tertile of L-GrAFT 7 was significantly associated with time to liver allograft (hazard ratio [HR] 2.17, p = 0.016), Clavien ≥IIIB (HR 2.60, p = 0.034) and ≥IVa (HR 4.99, p = 0.011) complications; post-LT length of hospitalization (p = 0.002); and renal replacement therapy (odds ratio 3.62, p = 0.016). We have validated the L-GrAFT 7 risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to existing scores. L-GrAFT 7 may standardize grading of early hepatic allograft function and serve as a clinical endpoint in translational studies (www.lgraft.com). Early allograft dysfunction negatively affects outcomes following liver transplantation. In independent multicenter US and European cohorts totaling 3,423 patients undergoing liver transplantation, the liver graft assessment following transplantation (L-GrAFT) risk score is validated as a superior measure of early allograft function that accurately discriminates 3-month graft failure-free survival and post-liver transplantation complications. [Display omitted] • Early allograft dysfunction negatively impacts graft and patient outcomes. • L-GrAFT assesses early allograft function based on post-transplant liver function tests. • L-GrAFT was validated as an accurate measure of graft survival, outperforming early allograft dysfunction. • L-GrAFT may be used as an accurate translational end-point in clinical trials. [ABSTRACT FROM AUTHOR]