Donor eligibility criteria and liver graft acceptance criteria during normothermic regional perfusion: A systematic review

Abstract

Acceptance of liver grafts from donations after circulatory death (DCD) largely remains a “black box,” particularly due to the unpredictability of the agonal phase. Abdominal normothermic regional perfusion (aNRP) can reverse ischemic injury early during the procurement procedure, and it simultaneously enables graft viability testing to unravel this black box. This review evaluates current protocols for liver viability assessment to decide upon acceptance or decline during aNRP. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guideline was used, and relevant literature databases were searched. The primary outcome consisted of criteria for liver graft viability assessment. Secondary outcomes included survival, primary nonfunction (PNF), early dysfunction, and biliary complications. A total of 14 articles were included in the analysis. In all protocols, a combination of criteria was used to assess suitability of the liver for transplantation. As many as 12 studies (86%) used macroscopic assessment, 12 studies (86%) used alanine transaminase (ALT) levels in perfusate, 9 studies (64%) used microscopic assessment, and 7 studies (50%) used lactate levels as assessment criteria. The organ utilization rate (OUR) was 16% for uncontrolled donation after circulatory death (uDCD) and 64% for controlled donation after circulatory death (cDCD). The most used acceptation criterion in uDCD is ALT level (31%), while in cDCD macroscopic aspect (48%) is most used. Regarding postoperative complications, PNF occurred in 13% (6%–25%) of uDCD livers and 3% (2%–4%) of cDCD livers. In uDCD, the 1‐year graft and patient survival rates were 75% (66%–82%) and 82% (75%–88%). In cDCD, the 1‐year graft and patient survival rates were 91% (89%–93%) and 93% (91%–94%), respectively. In conclusion, the currently used assessment criteria consist of macroscopic aspect and transaminase levels. The acceptance criteria should be tailored according to donor type to prevent an unacceptable PNF rate in uDCD and to increase the relatively modest OUR in cDCD.

The role of sequential normothermic regional perfusion and end‐ischemic normothermic machine perfusion in liver transplantation from very extended uncontrolled donation after cardiocirculatory death

“…The possibility to expand the graft utilization with additional NMP requires the definition of universally accepted selection parameters with the highest possible specificity, while we still rely on center‐based viability criteria. Considering our experience, another potential limitation to NMP‐facilitated assessment of uDCD liver grafts is the lack of biliary assessment, but recent data showed that these patients have a very low risk of IC and a much higher risk of graft loss in the early perioperative period 7 …”

“…In Italy, the most frequent approach to facilitate uDCD LT is sequential combination of pre‐procurement NRP and end‐ischemic, ex‐situ HMP. This strategy is based on the advantages of either technology in ensuring graft viability in the presence of long WIT (up to 170 min) and can overturn some limitations of uDCD 4,6,7 . In this scenario, graft selection is usually based on integration of NRP data (as per flow rate), metabolic parameters (lactate clearance), surrogate markers of liver injury (transaminases), and liver biopsy.…”

“…This strategy is based on the advantages of either technology in ensuring graft viability in the presence of long WIT (up to 170 min) and can overturn some limitations of uDCD. 4,6,7 In this scenario, graft selection is usually based on integration of NRP data (as per flow rate), metabolic parameters (lactate clearance), surrogate markers of liver injury (transaminases), and liver biopsy. However, graft evaluation during NRP is a challenging process due to the impact of technical (e.g., mode and timing of NRP) and biologic confounding factors (e.g., small-bowel or thoracic organ ischemia; fluid and blood products administration; electrolyte balance) on lactates, pH, and liver metabolism.…”

“…6 However, there is a paucity of data on sequential use of NRP and NMP in the setting of uDCD. 5,7 Although more challenging than HMP, NMP allows dynamic evaluation of graft viability, and the sequential combination of NRP and NMP has the potential to further expand graft viability criteria and acceptance rate.…”

Machine Perfusion for Extended Criteria Donor Livers: What Challenges Remain?

“…During NRP, the abdominal organs release the well-known proinflammatory molecules of IRI, and some are used to assess and predict the liver performance after later implantation [ 112 , 117 ]. In addition to liver macroscopy and biopsy, perfusate lactate and transaminases are routinely measured with various guidelines in different countries [ 116 , 120 ].…”