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

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Early allograft dysfunction (EAD) following liver transplantation (LT) negatively impacts graft and patient outcomes. The Liver Graft Assessment Following Transplantation (L-GrAFT7) risk-score estimates 3-month graft-failure-free survival (area under the receiver operator characteristic [AUROC] curve=0.83), and was superior to the binary EAD (AUROC=0.68) definition and Model for Early Allograft Function (MEAF, AUROC=0.70) in the single-center derivation cohort (DC, n=2008). We sought to externally validate L-GrAFT7, and compare its prognostic performance to EAD and MEAF.Accuracies of L-GrAFT7, EAD, and MEAF were compared in a 3-center US validation cohort (VC, n=3201), and Consortium for Organ Preservation in Europe (COPE) normothermic machine perfusion trial cohort (n=222), with comparison of characteristics to assess generalizability.Compared to the DC, VC and COPE patients had lower recipient median MELD scores (18 and 14 vs 31); were less likely to require pretransplant hospitalization (23.3% and 0% vs 46.1%), renal replacement therapy (8.8% and 1.8% vs 31.7%), mechanical ventilation (3.7% and 0% vs 19.8%); 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-GrAFT7 maintained an excellent validation AUROC of 0.78, significantly superior to the EAD (AUROC=0.68, P=0.001) and MEAF scores (AUROC=0.72, P<0.001). In post-hoc analysis of COPE NMP trial, highest tertile of L-GrAFT7 was significantly associated with time to liver allograft (HR 2.17, P=0.016) and Clavien ≥IIIB (HR 2.60, P=0.034) and ≥IVa (HR 4.99, P=0.011) complications, and post-LT length of hospitalization (P=0.002) and renal replacement therapy (OR 3.62, P=0.016).We have validated the L-GrAFT7 risk score as a generalizable, highly accurate, individualized risk assessment of 3-month liver allograft failure that is superior to the existing EAD and MEAF scores. L-GrAFT7 may standardize grading of early hepatic allograft function, and serve as a clinical end-point in translational studies aiming to mitigate ischemia-reperfusion injury.Early allograft dysfunction negatively affects outcomes following liver transplantation (LT). In independent multicenter US and European cohorts totaling 3423 patients undergoing LT, 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-LT complications.

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