Reassessment of Relevance and Predictive Value of Parameters Indicating Early Graft Dysfunction in Liver Transplantation: AST Is a Weak, but Bilirubin and INR Strong Predictors of Mortality.

Margot Fodor,Dietmar Öfner,Robert Sucher,Adriana Woerdehoff,Manuel Maglione,Annemarie Weissenbacher,Hannah Esser,Thomas Resch,Christian Margreiter,Wolfgang Peter,Rupert Oberhuber,Heinz Zoller,Stefan Schneeberger,Benno Cardini,Herbert Tilg

doi:10.3389/fsurg.2021.693288

Margot Fodor, Dietmar Öfner + Show 13 more

Open Access

https://doi.org/10.3389/fsurg.2021.693288

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Abstract

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels >2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.

Highlights

Graft dysfunction (EAD) complicates liver transplantation (LT)
The most widely used definition of early graft dysfunction (EAD) was introduced by Olthoff et al working from 300 LT recipients at three different sites in the United States and includes (i) bilirubin ≥ 10 mg/dL on postoperative day 7; (ii) international normalized ratio (INR) ≥ 1.6 on postoperative day 7; (iii) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2,000 IU/mL within the first 7 days [12]
We hypothesize that the Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; body mass index (BMI), Body mass index; cold ischemia time (CIT), Cold ischemia time; donation after cardiac death (DCD), Donors after cardiac death; DBD, Donors after brain death; donor risk index (DRI), Donor risk index; EAD, Early graft dysfunction; INR, International normalized ratio; L-GrAFT, Liver Graft Assessment Following Transplantation, LT, Liver transplantation, MEAF, Model for Early Allograft Function, model for endstage liver disease (MELD), Model for end-stage liver disease

Summary

Introduction

Graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival. The most widely used definition of EAD was introduced by Olthoff et al working from 300 LT recipients at three different sites in the United States and includes (i) bilirubin ≥ 10 mg/dL on postoperative day 7; (ii) international normalized ratio (INR) ≥ 1.6 on postoperative day 7; (iii) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2,000 IU/mL within the first 7 days [12] Since this definition of EAD is used as an endpoint in clinical and translational studies, it is important to determine the predictive value for the eventual outcome. The relevance of a binary categorization of patients on the long-term outcome and the weighting and interpretation of the individual parameters is lacking This issue has recently attracted attention, since the introduction of novel techniques to improve organ preservation such as machine perfusion [5, 13], and the increasing use of livers from DCD donors require early clinical endpoints for assessment of the benefit. We hypothesize that the Abbreviations: ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; BMI, Body mass index; CIT, Cold ischemia time; DCD, Donors after cardiac death; DBD, Donors after brain death; DRI, Donor risk index; EAD, Early graft dysfunction; INR, International normalized ratio; L-GrAFT, Liver Graft Assessment Following Transplantation, LT, Liver transplantation, MEAF, Model for Early Allograft Function, MELD, Model for end-stage liver disease

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