Clinical heterogeneity in binary EAD definition and proposal of new EAD classification after liver transplantation: A multicenter study

Background&Aims: Current binary definition of early allograft dysfunction (EAD) was not sufficiently accurate for discriminating clinical outcomes after liver transplantation (LT). We investigated the clinical heterogeneity among EAD sub-criteria and explored the necessity of dividing EAD into different stages to grade the severity of graft dysfunction. Methods: 1242 LT patients from 5 centers were included. EAD patients were divided as i) EAD-type-A: only AST/ALT criteria; ii) EAD-type-B: bilirubin or INR criteria; iii) EAD-type-C: meeting two or three EAD sub-criteria. Peri-operative clinical complications and survival outcomes were compared. Results: Three-month early graft failure (EAF) from non-EAD to EAD-type-C were 1.6%, 3.5%, 12.8% and 29.6%. EAD-type-B and EAD-type-C were significantly associated with higher rates of AKI, RRT, in-hospital death, longer hospital stay, ICU stay, ventilator support time, and inferior one-year survival outcomes(P<0.001); However, there were no statistical differences between EAD-type-A and non-EAD (P>0.05). New EAD classification with three stages was proposed to grade EAD severity: a)EAD-stage-I: only ALT/AST≥2000 U/L within POD7; b)EAD-stage-II: only bilirubin 10-30 mg/dL or INR≥1.6 on POD7; c)EAD-stage-III: bilirubin≥30 mg/dL; both bilirubin≥10 mg/dL and INR≥1.6 on POD7. Clinical outcomes and survival rates deteriorated following EAD stages. New EAD classification had an excellent discrimination (AUROC = 0.84, CI 0.81-0.86) in determining EAF, superior to binary EAD definition (AUROC = 0.73, CI 0.70-0.77) and MEAF (AUROC = 0.76, CI 0.73-0.79) (P<0.001), while similar to L-GrAFT-7(AUROC = 0.87, CI = 0.84-0.90 P>0.05). Consistent with findings in derivation cohort, external validation confirmed its excellent discrimination of graft dysfunction and 3-month EAF. Conclusions: Different EAD sub-criteria had significantly different clinical outcomes. EAD definition should be further reclassified with different severities. New EAD classification with 3 stages could be serve as an effective tool to accurately grade the severity of EAD and identify patients in high risk of early graft failure.