Different severity and disparate clinical outcomes between EAD sub-criteria and proposal of a new EAD classification after liver transplantation
Yu Nie1, Jinbo Huang2,3,4, Shujiao He2,3,4, Huadi Chen2,3,4, Junjun Jia5, Xiaoshun He2,3,4, Qiang Zhao2,3,4.
1General Surgery Center, Zhujiang Hospital of Southern Medical University, Guangzhou, People's Republic of China; 2Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People's Republic of China; 3Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Sun Yat-sen University, Guangzhou, People's Republic of China; 4Guangdong Provincial International Cooperation Base of Science and Technology, Sun Yat-sen University, Guangzhou, People's Republic of China; 5Division of Hepatobiliary and Pancreatic Surgery, Prople's Hospital of Zhejiang Province, Hangzhou, People's Republic of China
Background: The current binary definition of early allograft dysfunction (EAD) is not sufficiently accurate for discriminating clinical outcomes after liver transplantation (LT). It is also criticized for including heterogeneous diagnostic criteria with disparate severities of clinical outcomes. We investigated whether there are significant differences in clinical outcomes among three EAD sub-criteria and explore the necessity of dividing EAD into different stages like acute kidney injury to grade the severity of graft dysfunction.
Methods: A total of 707 consecutive LT patients from 2015 to 2020 were retrospectively reviewed. EAD patients were divided into 3 subgroups based on different sub-criteria: i) EAD-type-A: only elevated AST/ALT>2000 U/L within postoperative day 7(POD 7); ii) EAD-type-B: bilirubin ≥10 mg/dL or INR≥1.6 on POD 7; iii) EAD-type-C, meeting two or three of the bilirubin, INR and ALT/AST criteria. Peri-operative clinical complications and survival outcomes were compared between these subgroups.
Results: Three-month graft failure in non-EAD, EAD-type-A, EAD-type-B and EAD-type-C were 1.6%, 3.5%, 12.8% and 29.6%; One-year patient survival was 94.6%, 93.6%, 81.3% and 71.2%, respectively. EAD-type-B and EAD-type-C were significantly associated with longer hospital stay, ICU stay, ventilator support time, higher rates of AKI, RRT, in-hospital death, and inferior one-year survival outcomes(P<0.001); However, there were no statistical differences between non-EAD and EAD type A(P>0.05). A new EAD classification with three stages was reclassified to grade the severity of post-LT graft dysfunction. In ROC analysis, new EAD classification had an excellent overall AUROC of 0.84(0.81-0.86) in determining 3-month graft failure, superior to the binary EAD (AUROC=0.73, CI 0.70-0.77, P<0.001) and Model for Early Allograft Function Scoring(MEAF) (AUROC=0.76,CI 0.73-0.79, P<0.001), while similar to the Liver Graft Assessment Following Transplantation score(L-GrAFT-7) (AUROC=0.87, CI=0.84-0.90, P>0.05).
Conclusions: Different EAD sub-criteria experienced significantly different clinical outcomes. The binary EAD definition could be further reclassified into several sub-stages with different severity. The new EAD with 3 stages could serve as an effective tool to simply stratify the severity of graft dysfunction after LT.
National Natural Science Foundation of China (81570587 and 81700557). Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (2013A061401007 and 2017B030314018). Guangdong Provincial Natural Science Funds for Major Basic Science Culture Project (2015A030308010). Guangdong Provincial Funds for High-end Medical Equipment (2020B1111140003). Science and Technology Program of Guangzhou (201704020150). Natural Science Foundations of Guangdong province (2016A030310141 and 2020A1515010091). Young Teachers Training Project of Sun Yat-Sen University (K0401068) . Colin New Star of Sun Yat-Sen University (R08027).
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