Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation From Donors After Brain Death: A Randomized Controlled Trial

Ann Surg. 2023 Nov 1;278(5):662-668 doi: 10.1097/SLA.0000000000006055.
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).

BACKGROUND:

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 hours 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 groups ( 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). Transaminase activity, bilirubin concentration, and international normalized ratio were similar in both 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.

CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This small, randomised control trial looked at early post-transplant outcomes after dHOPE compared with SCS in an undifferentiated group of DBD livers. They found no significant difference in their primary outcome of MEAF score between the two groups. They also found no difference in all grades of complications, mortality, post-reperfusion syndrome rates, comprehensive complications index (CCI), L-GrAFT7, or the other non-prespecified secondary outcomes, ITU stay, PNF, EAD and EASE score. The lack of significant benefits were similar to that seen in Schlegal et al’s recent larger multicentre randomised trial who used CCI as their primary outcome. In this study, only 26 livers were in the intervention group and they were hoping to detect a MEAF score reduction of 1.5, a delta in primary outcome of no specific significance. The small number and lack of power calculation has meant there is significant risk of falsely negative findings. They performed a sub-group analysis, dividing the livers arbitrarily by DRI, with a cut-off of >1.7 as becoming ‘high-risk’, within this group dHOPE caused a significant reduction in MEAF score (4.92 vs 6.31, p=0.037) and in CCI (p=0.05). This led the authors to conclude that routine use of dHOPE is not recommended in DBD livers, only for those deemed ‘high-risk’. Again, caution is needed with the conclusion that there is no benefit in lower risk livers, given only 12 and 14 livers were in the DRI ≤1.70 and DRI >1.70 respectively. The trial is appropriately randomised, but was not blinded due to logistical reasons, which with a device trial of this nature is challenging. There is no information given regarding drop-outs or protocol breaches. The area of investigation is interesting and a valid research question, however, this trial is not sufficiently powered to be relied upon as a negative study. They have highlighted a potential difference in benefit, or lack there of depending on the quality of donor, and future studies should consider this and power specifically for sub-group analysis.
Methodological quality
Jadad score 3
Allocation concealment YES
Data analysis INTENTION TO TREAT
Study Details
Aims: To assess if dual hypothermic oxygenated perfusion (dHOPE) prior to transplantation improves the Model for Early Allograft Function (MEAF) score during the 72 hours following transplant compared with static cold storage (SCS).
Interventions: The intervention group received at least 2 hours of dHOPE prior to transplantation, and the control group underwent standard SCS.
Participants: 104 adult whole liver transplant recipients from donation after brainstem death.
Outcomes: The primary outcome was MEAF score during the 72 hours post transplant. Secondary outcomes were complications over 90-days, 7-day liver graft assessment following transplantation (L-GrAFT7), post-reperfusion syndrome rate, comprehensive complication index (CCI) and mortality.
Follow Up: Not reported
Metadata
Funding: Non-industry funding
Publication type: Randomized Controlled Trial, Randomised Controlled Trial
Trial registration: ClinicalTrials.gov - NCT04812054
Organ: Liver
Language: English
Author email: michal.grat@gmail.com
MeSH terms: Humans; Liver Transplantation; Brain Death; Organ Preservation; Graft Survival; Tissue Donors; Liver; Perfusion