Predictive value of early lactate (<6 h) during normothermic machine perfusion and outcome after liver transplantation: results from a multicentre study

Author:

Hofmann Julia1ORCID,Meszaros Andras T1ORCID,Butler Andrew2,Hann Angus3,Hartog Hermien3,Kneifel Felicia4,Iype Satheesh5ORCID,Crick Keziah5,Cardini Benno1,Fiore Barbara6,Attia Magdy6,Pollok Joerg-Matthias57ORCID,Pascher Andreas4,Vogel Thomas4,Perera Thamara3ORCID,Watson Christopher J E2,Schneeberger Stefan1ORCID

Affiliation:

1. Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck , Innsbruck , Austria

2. Department of Surgery, University of Cambridge , Cambridge , UK

3. Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust (UHBFT) , Birmingham , UK

4. Department of General, Visceral and Transplant Surgery, University Hospital of Münster (UKM) , Münster , Germany

5. Department of HPB and Liver Transplantation, The Royal Free Hospital , Hampstead, London , UK

6. Liver Transplant Unit, Leeds Teaching Hospitals, NHS Foundation Trust , Leeds , UK

7. Division of Surgery and Interventional Science, University College London , London , UK

Abstract

Abstract Background Biomarkers with strong predictive capacity towards transplantation outcome for livers undergoing normothermic machine perfusion (NMP) are needed. We investigated lactate clearing capacity as a basic function of liver viability during the first 6 h of NMP. Methods A trial conducted in 6 high-volume transplant centres in Europe. All centres applied a back-to-base NMP approach with the OrganOx metra system. Perfusate lactate levels at start, 1, 2, 4 and 6 h of NMP were assessed individually and as area under the curve (AUC) and correlated with EAD (early allograft dysfunction), MEAF (model for early allograft function) and modified L-GrAFT (liver graft assessment following transplantation) scores. Results A total of 509 livers underwent ≥6 h of NMP before transplantation in 6 centres in the UK, Germany and Austria. The donor age was 53 (40–63) years (median, i.q.r.). The total NMP time was 10.8 (7.9–15.7) h. EAD occurred in 26%, MEAF was 4.72 (3.54–6.05) and L-GrAFT10 −0.96 (−1.52–−0.32). Lactate at 1, 2 and 6 h correlated with increasing robustness with MEAF. Rather than a binary assessment with a cut-off value at 2 h, the actual 2 h lactate level correlated with the MEAF (P = 0.0306 versus P = 0.0002, Pearson r = 0.01087 versus r = 0.1734). The absolute lactate concentration at 6 h, the AUC of 0–6 h and 1–6 h (P < 0.0001, r = 0.3176) were the strongest predictors of MEAF. Conclusion Lactate measured 1–6 h and lactate levels at 6 h correlate strongly with risk of liver allograft dysfunction upon transplantation. The robustness of predicting MEAF by lactate increases with perfusion duration. Monitoring lactate levels should be extended to at least 6 h of NMP routinely to improve clinical outcome.

Funder

National Institute for Health Research Blood and Transplant Research Unit

NHS Blood and Transplant

NIHR Cambridge Biomedical Research Centre

Royal Free Liver Transplant Department

Publisher

Oxford University Press (OUP)

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