Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation from Donors After Brain Death

Abstract

Objective: To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD). Summary Background Data: There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors. Methods: In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 h or SCS ( 1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity. (ClinicalTrials. gov, NCT04812054). Results: Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS group (P=0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P=0.18). Median comprehensive complication index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS (P=0.19). Transaminases activity, bilirubin concentration, and international normalized ratio were similar in both the groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs. 6.31; P=0.037) and lower median comprehensive complication index (4.35 vs. 22.6; P=0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values. Conclusion: Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.

Back to Basics: Liver Graft Ischemia in the Era of Machine Perfusion

“…The first scenario is endischemic HOPE with low SCI reduction that has been shown to reduce nonanastomotic biliary strictures in DCD livers but has failed to show a benefit in DBD livers (Figure 1A). 1,5,7 We can conclude that end-ischemic HOPE with low SCI reduction may be a promising strategy to protect the bile ducts in DCD liver grafts. In contrast, end-ischemic HOPE with high SCI reduction has been shown to reduce post-LT complications and EAD in DBD livers and may be an interesting strategy for marginal DBD grafts with expected long preservation with SCS (Figure 1B).…”

“…2,3,9 In the 5 RCTs using HOPE, there is a large variation in SCI reduction, and we may distinguish 2 different subgroups. In the trials by Schlegel et al, 1 Grat et al, 7 and Van Rijn et al, 5 reduction of SCI is ≤25%, whereas in the studies by Czigany et al 4 and Ravaioli et al 8 reduction in SCI is ≥25% (25% and 39%, respectively).…”

“…A total of 9 major randomized controlled trials (RCTs) comparing various MP strategies to the gold standard static cold storage (SCS) have been published to date. [1][2][3][4][5][6][7][8][9] In the following, we provide an alternative analysis of the available RCT data by focusing on liver graft ischemia before MP, with the aim of establishing an updated classification of available dynamic preservation strategies in liver transplantation (LT). 10…”

Routine utilization of machine perfusion in liver transplantation: Ready for prime time?

“…In low-risk DBD donors HOPE had no impact on outcomes, however authors demonstrated significantly lower EAD-rates and post-operative complications in donor livers with higher risk, i.e. , with a donor risk index of > 1.7)[ 14 ]. Two additional RCTs were recently presented with NMP and HOPE in the United States.…”

Improved outcomes after hypothermic oxygenated machine perfusion in liver transplantation–Long-term follow-up of a multicenter randomized controlled trial

“… 11 The potent clinical effects of HOPE, especially when using high-risk livers, have been described consistently in 5 randomized controlled clinical trials (RCT). 8 – 10 , 12 – 14 These trials could demonstrate a reduction of early allograft injury, 10 , 13 , 14 cumulative morbidity, 13 , 14 liver-related complications, 8 length of stay, 13 treatment costs, 15 , 16 and a mitigating effect on nonanastomotic biliary complications in donation after circulatory death (DCD) when using HOPE-treated allografts. 9 The most recent trial published very recently by Grąt et al 14 from Warsaw could also confirm the short-term benefits of HOPE on early allograft dysfunction and morbidity in high-risk livers with donor risk index over 1.7, but not for standard criteria allografts.…”