Routine end-ischemic hypothermic machine perfusion in liver transplantation from donors after brain death: results of two-year follow-up of a randomized controlled trial.
Morawski, M., et al.International Journal of Surgery 2024 [record in progress].
Aims
To assess if routine dual hypothermic machine perfusion (dHOPE) is beneficial in a cohort of donors after brain death (DBD) livers, in both lower and higher risk liver transplants.
Interventions
Comparing end-ischaemic dual portal and arterial hypothermic oxygenated perfusion (dHOPE) versus static cold storage (SCS).
Participants
104 adult whole liver recipients (78 SCS, 26 dHOPE).
Outcomes
The primary endpoint measure of the initial trial was model of early allograft function (MEAF) score. The secondary endpoints included 2-year graft and patients survival, and biliary complications.
Follow-up
2 years
CET Conclusions
The authors present long term (2-year) outcome data from their previously published RCT on ‘routine’ end-ischaemic dHOPE vs SCS in a modest cohort of DBD livers. The authors performed end ischaemic dHOPE in 26 livers using the XVIVO device with the MEAF score as the primary outcome. In the early results published 2023 the MEAF score was lower with dHOPE, but insignificant, and all other secondary outcomes failed to reach significance. Now with 2-year follow-up data they conclude, is align with other historic studies, there is likely to be benefit in the higher risk DBD donors, but not in lower risk livers and would not consider HOP for routine use. The trial was randomised 1:3 of dHOPE:SCS, meaning only 26 livers received dHOPE, leaving the study underpowered for longer term biliary complications in a DBD only cohort. This could have been accounted for if they had based their delta on the effect sizes seen in previous RCTs in high-risk livers, under the assumption that effects are likely to be more modest in lower risk DBD donors the cohort size would require increasing. Within their study for every reported biliary complication, the incidence was numerically lower in the dHOPE livers, and the 2-year graft and patient survival higher, but only reaching statistical significance for graft and patient survival in subgroup analysis of there higher risk livers, in which all livers and patients (100%) were alive at the 2-year point vs a graft survival of 73.1% and a patient survival of 76.9% in the SCS cohort. The study has value in providing further numbers for future meta-analysis, but their conclusion of HOPE not being for routine use is not a sound one. The most recent meta-analysis by Liang, A. et al. was published the same year as the initial RCT but does not contain its data. The meta-analysis does contain 14 studies including 5 of the 6 RCTs done to date. They find benefit across all donor types with an amplified benefit in the higher risk donors. Therefore, it does seem reasonable to think that given the trend in numbers seen in this RCT, that had it been appropriately powered for biliary complications and with stratified randomisation for projected subgroup analysis of higher and lower DRI livers more significant findings could have been made. Given they had a relatively robustly designed RCT in Poland’s largest liver transplant unit, they would have only required 6-12months further recruitment to reach the likely numbers required and led to a much more comprehensive and definitive piece of work.
Trial registration
ClinicalTrials.gov - NCT04812054