Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts the Outcome of Recipients after Liver Transplantation

Abstract

Background: Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis of both recipients and grafts. This study aims to explore the relationship between pretransplant intrahepatic protein profiles and the onset of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. Methods: Liver biopsy specimens of 105 pretransplant grafts used for LT were collected and used for immunohistochemistry analysis of 5 proteins. And matched clinical data of donor, recipient, transplantation and prognosis was analyzed. Findings: The incidence of EAD was 41·9% (44/105) in this cohort. Macrovesicular steatosis (P=0·016), donor body mass index (P=0·013), recipients’ pretransplant serum creatinine (P=0·036), and the intrahepatic expression of heme oxygenase 1 (HO1) (P=0·015) and tumor necrosis factor α (TNF-α) (P=0·039) were independent predictors of the onset of EAD. Inferior graft and recipient prognosis were observed in patients experienced EAD (P=0·028 and 0·031, respectively) or received grafts with higher expression of Sirtuin 1 (P=0·005 and 0·013, respectively). The graft and recipient survival were worst in patients with both EAD development and high expression of Sirtuin 1 (P=0·001 and 0·004, respectively). Interpretation: Pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated protein profiles showed superiority in distinguishing recipients with potential worse prognosis. Funding: National Natural Science Foundation of China, Key Research & Development Plan of Zhejiang Province, and Projects of Medical and Health Technology Program in Zhejiang Province. Declaration of Interest: None to declare. Ethical Approval: The procurement of donor grafts was performed in accordance with the national guidelines for DCD in China. The procedure has been described in our previous studies (5). Each organ donation or transplant was approved by the Institutional Review Board, Zhejiang University school of medicine, strictly under the guidelines of the Ethics Committee of the hospital, the current regulation of the Chinese Government, and the Declaration of Helsinki. Informed consent in writing was obtained from each patient. And no organs from executed prisoners were used.