Combination of Early Allograft Dysfunction and Protein Expression Patterns Predicts Outcome of Liver Transplantation From Donation After Cardiac Death.

Qiang Wei,Kun Wang,Junli Chen,Xuanyu Zhang,Junbin Zhou,Xiao Xu,Xuyong Wei,Shusen Zheng,Di Lu

doi:10.3389/fmed.2021.775212

Abstract

Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis. This study aims to explore the relationship between pretransplant intrahepatic proteins and the incidence of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. 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 were analyzed. 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 intrahepatic expression of heme oxygenase 1 (HO1) (P = 0.015) and tumor necrosis factor α (TNF-α) (P = 0.039) were independent predictors of EAD. Inferior graft and recipient prognosis were observed in patients who experienced EAD (P = 0.028 and 0.031) or received grafts with higher expression of sirtuin 1 (P = 0.005 and 0.013). The graft and recipient survival were worst in patients with both EAD and high expression of sirtuin 1 (P = 0.001 and 0.004). In conclusion, pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated proteins showed superiority in distinguishing recipients with worse prognosis.

Highlights

Liver transplantation (LT) has been accepted as the only available curative treatment for patients with end-stage liver disease
Macrovesicular steatosis ≥ 30% (P = 0.005), higher model for end-stage liver disease (MELD) score (P = 0.006), and longer cold ischemic time (CIT) (P = 0.001) were identified as risk factors associated with the onset of Early allograft dysfunction (EAD)
The results showed that macrovesicular steatosis ≥ 30% (OR = 0.039, 95% CI = 1.39225.843, P = 0.016), pretransplant serum creatinine (OR = 1.012, 95% CI = 1.001–1.023, P = 0.036), and donor body mass index (BMI) (OR = 1.007, 95% CI = 1.002–1.013, P = 0.013) were independent predictors of EAD development

Summary

Introduction

Liver transplantation (LT) has been accepted as the only available curative treatment for patients with end-stage liver disease. With rapidly increasing demand for LT, there is a serious shortage of donor organs. This has promoted the usage of marginal or extended criteria donors such as donation after cardiac death (DCD), steatosis, and senile donor livers. The use of these suboptimal grafts leads to higher morbidity and mortality of recipients. The usage of marginal or extended criteria donors have increased the incidence of EAD [2]. EAD is reversible, it could deteriorate into primary non-function, demanding re-transplantation or leading to death. Recipients or grafts experiencing EAD tend to have an inferior survival prognosis [3, 4]

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Conclusion