Normothermic Perfusion in the Assessment and Preservation of Declined Livers Before Transplantation

Abstract

BackgroundA program of normothermic ex situ liver perfusion (NESLiP) was developed to facilitate better assessment and use of marginal livers, while minimizing cold ischemia.MethodsDeclined marginal livers and those offered for research were evaluated. Normothermic ex situ liver perfusion was performed using an erythrocyte-based perfusate. Viability was assessed with reference to biochemical changes in the perfusate.ResultsTwelve livers (9 donation after circulatory death [DCD] and 3 from brain-dead donors), median Donor Risk Index 2.15, were subjected to NESLiP for a median 284 minutes (range, 122-530 minutes) after an initial cold storage period of 427 minutes (range, 222-877 minutes). The first 6 livers were perfused at high perfusate oxygen tensions, and the subsequent 6 at near-physiologic oxygen tensions. After transplantation, 5 of the first 6 recipients developed postreperfusion syndrome and 4 had sustained vasoplegia; 1 recipient experienced primary nonfunction in conjunction with a difficult explant. The subsequent 6 liver transplants, with livers perfused at lower oxygen tensions, reperfused uneventfully. Three DCD liver recipients developed cholangiopathy, and this was associated with an inability to produce an alkali bile during NESLiP.ConclusionsNormothermic ex situ liver perfusion enabled assessment and transplantation of 12 livers that may otherwise not have been used. Avoidance of hyperoxia during perfusion may prevent postreperfusion syndrome and vasoplegia, and monitoring biliary pH, rather than absolute bile production, may be important in determining the likelihood of posttransplant cholangiopathy. Normothermic ex situ liver perfusion has the potential to increase liver utilization, but more work is required to define factors predicting good outcomes.

Liver Grafts From Donors After Circulatory Death on Regional Perfusion With Extended Warm Ischemia Compared With Donors After Brain Death

“…Although serum lactate is considered to be a marker of adequate perfusion and hepatic clearance, these groups have placed little importance on this factor, probably because its concentration during NRP may be altered by reflux from extra‐abdominal regions . Recent studies on normothermic machine perfusion have used serum lactate levels for ex situ evaluation . In our study, although levels exceeded the above‐mentioned limits, ALT did not exhibit a clear relationship to the transplant outcomes.…”

The future of organ perfusion and re‐conditioning

“…Normothermic machine perfusion has been the subject of most interest in liver transplantation and recently, Jassem et al . have provided a much needed mechanistic insight into NMP in liver transplantation by demonstrating an altered gene expression profile in NMP compared with cold‐stored livers from pro‐inflammation to pro‐healing and regeneration.…”

Transient Cold Storage Prior to Normothermic Liver Perfusion May Facilitate Adoption of a Novel Technology

“…Blood gas analysis, sampled from an outlet via the hepatic artery line, was performed after 15 minutes and 1 hour from the beginning of perfusion and then at least every 4 hours until the end of perfusion. Functional parameters were available to the transplanting surgeon, as previously described, and they included the following: lactate clearance, glucose metabolism, pH maintenance, bile production, perfusate transaminase levels, and flow rates . The final decision to transplant the liver was made by the transplanting surgeon.…”