Introduction of the Concept of Diagnostic Sensitivity and Specificity of Normothermic Perfusion Protocols to Assess High‐Risk Donor Livers

Abstract

Normothermic machine perfusion (NMP) allows objective assessment of donor liver transplantability. Several viability evaluation protocols have been established, consisting of parameters such as perfusate lactate clearance, pH, transaminase levels, and the production and composition of bile. The aims of this study were to assess 3 such protocols, namely, those introduced by the teams from Birmingham (BP), Cambridge (CP), and Groningen (GP), using a cohort of high‐risk marginal livers that had initially been deemed unsuitable for transplantation and to introduce the concept of the viability assessment sensitivity and specificity. To demonstrate and quantify the diagnostic accuracy of these protocols, we used a composite outcome of organ use and 24‐month graft survival as a surrogate endpoint. The effects of assessment modifications, including the removal of the most stringent components of the protocols, were also assessed. Of the 31 organs, 22 were transplanted after a period of NMP, of which 18 achieved the outcome of 24‐month graft survival. The BP yielded 94% sensitivity and 50% specificity when predicting this outcome. The GP and CP both seemed overly conservative, with 1 and 0 organs, respectively, meeting these protocols. Modification of the GP and CP to exclude their most stringent components increased this to 11 and 8 organs, respectively, and resulted in moderate sensitivity (56% and 44%) but high specificity (92% and 100%, respectively) with respect to the composite outcome. This study shows that the normothermic assessment protocols can be useful in identifying potentially viable organs but that the balance of risk of underuse and overuse varies by protocol.

Normothermic liver machine perfusion as a dynamic platform for regenerative purposes: What does the future have in store for us?

“…Currently, (non-validated) hepatocellular and/or cholangiocellular viability markers are used. 110,111 However, when using NMP for repair and regeneration, new biomarkers will have to be identified to act as viability criteria in order to evaluate the effect of the treatments in addition to the current criteria (Box 1).…”

Normothermic Machine Perfusion—Improving the Supply of Transplantable Livers for High-Risk Recipients

“…Many different institutions have reported the criteria they apply to determine if a graft is viable, and these are being constantly altered to reflect the growing experience ( 12 , 13 , 28 , 32 – 34 ). These have been extensively reviewed by other authors ( 35 – 37 ). The different markers reportedly used for graft assessment during NMP can be considered as surrogate indicators of graft injury and hepatocellular or cholangiocyte function ( Figure 2 ).…”

Perfusion Programmes Start-Up and Viability Assessment: A Practical Guide to Ex-Situ Normothermic Machine Perfusion in Liver Transplantation

“…Importantly, bile composition may help to identify livers at risk of developing late biliary NAS that is of key importance in DCDs. Its role in assessment of DBD livers is of lesser importance, with the main drawbacks being the delayed production and possible failure due to technical complications 10,27,48 . A lag in recovery of the production can be often observed in steatotic livers or organs following extensive CIT with the times being beyond the widely accepted 2-4 hours viability assessment timeframe.…”

“…Retrospective analyses of collected samples confirmed those were present in livers without bile production, low bile pH or bile bicarbonate. Overall, bile production and bile analysis seem to be of paramount importance to assess biliary integrity to predict DCD livers longevity and avoid NAS 8,48 .…”