Biliary Bicarbonate, pH, and Glucose Are Suitable Biomarkers of Biliary Viability During Ex Situ Normothermic Machine Perfusion of Human Donor Livers

Alix P M Matton, Yvonne de Vries, Laura C Burlage, Rianne van Rijn, Masato Fujiyoshi, Vincent E de Meijer, Marieke T de Boer, Ruben H J de Kleine, Henkjan J Verkade, Annette S H Gouw, Ton Lisman, Robert J Porte

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BACKGROUND: Ex situ normothermic machine perfusion (NMP) can be used to assess viability of suboptimal donor livers prior to implantation. Our aim was to assess the diagnostic accuracy of bile biochemistry for the assessment of bile duct injury (BDI).

METHODS: In a preclinical study, 23 human donor livers underwent 6 hours of end-ischemic NMP to determine biomarkers of BDI. Livers were divided into groups with low or high BDI, based on a clinically relevant histological grading system. During NMP, bile was analyzed biochemically and potential biomarkers were correlated with the degree of BDI. Receiver operating characteristics curves were generated to determine optimal cut-off values. For clinical validation, identified biomarkers were subsequently included as viability criteria in a clinical trial (n=6) to identify transplantable liver grafts with low BDI.

RESULTS: Biliary bicarbonate and pH were significantly higher and biliary glucose was significantly lower in livers with low BDI, compared to high BDI. The following cut-off values were associated with low BDI: biliary bicarbonate >18 mmol/L (P=0.002), biliary pH >7.48 (P=0.019), biliary glucose <16 mmol/L (P=0.013), and bile/perfusate glucose ratio <0.67 (P=0.013). In the clinical trial, 4 out of 6 livers met these criteria and were transplanted, and none developed clinical evidence of post-transplant cholangiopathy.

CONCLUSIONS: Biliary bicarbonate, pH, and glucose during ex situ NMP of liver grafts are accurate biomarkers of BDI and can be easily determined point-of-care, making them suitable for the pre-transplant assessment of bile duct viability. This may improve graft selection and decrease the risk of post-transplant cholangiopathy.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Original languageEnglish
Pages (from-to)1405-1413
Number of pages9
Issue number7
Early online date1-Nov-2018
Publication statusPublished - Jul-2019




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