Transplantation of discarded livers following viability testing with normothermic machine perfusion

Abstract

There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirtyone livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring retransplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia.

The Immunological Basis of Liver Allograft Rejection

“…Novel therapeutic strategies like ex vivo perfusion are already augmenting the pool of transplantable organs ( 164 ). Organ reconditioning strategies have already been applied in animal models to reduce the ischemia reperfusion injury by the infusion of MSCs or other anti-inflammatory agents ( 165 ) or to reduce steatosis using defatting agents before transplantation ( 166 ).…”

The Rise of the Machines: Will They Fulfill the Restoration Promise?

“…Reiling et al (4) 17 (14-26) 50% EAD, all grafts functioning, no DCD cholangiopathy Nasralla et al (5) Mergental et al (6) Bral et al (9) Schlegel et al (7) (2019) Viability Testing and Transplantation of Marginal Livers (VITTAL) trial by Mergental et al (6) did use NMP to monitor and revitalize discarded livers in the United Kingdom. EAD occurred in 32% of patients with 86% allograft survival at 1 year.…”

“…Taking all these studies together, it appears that NMP may not prevent the development of nonanastomotic biliary strictures in high-risk DCDs and that fWIT should not be extended beyond 30 minutes. (6) Proponents of HOPE suggest it induces changes in mitochondria that protect against cholangiopathy and oxidative injury. Boteon et al (8) Studied discarded livers using 6 hours of NMP alone (n = 5) and compared them with livers receiving 2 hours of HOPE followed by 4 hours of NMP (n = 5) in a nontransplant model.…”

“…Although this study confirmed the benefit of NMP in LT, it did not include already discarded livers for revitalization. The recently reported Viability Testing and Transplantation of Marginal Livers (VITTAL) trial by Mergental et al ( 6 ) did use NMP to monitor and revitalize discarded livers in the United Kingdom. EAD occurred in 32% of patients with 86% allograft survival at 1 year.…”

Preventing Tumour Recurrence after Liver Transplantation: The Role of Machine Perfusion

“…First, an immediate NMP after liver procurement with subsequent device transport and second, an endischemic NMP in the recipient centre with acceptance of a few hours of cold ischemia before starting the normothermic perfusion [11,107]. There is recent evidence that this endischemic approach may yield good outcomes in low risk DCD donor livers [108], while the recent work from Cambridge demonstrated inferiority of the endischemic NMP approach in DCD livers with advanced risk [107,109,110]. The feasibility of complete elimination of hypoxia via continuous NMP to prevent postreperfusion syndrome and IRI via ischaemia-free organ transplantation (IFOT), although it appears to be clinically possible, is challenging and limited.…”