Real-Time Biomarkers of Liver Graft Quality in Hypothermic Oxygenated Machine Perfusion.
Zhylko, A., et al.Journal of clinical medicine 2025; 14(2): 13.
Aims
To determine whether lactate concentration measured in real time during hypothermic oxygenated machine perfusion (HOPE) of liver grafts can serve as a biomarker to predict post-transplant graft function and early clinical outcomes.
Interventions
Intervention Group (dHOPE): Liver grafts underwent dual hypothermic oxygenated machine perfusion for ≥120 minutes (portal vein + hepatic artery perfusion). Control (SCS): A separate arm of patients received conventional static cold storage. The paper’s focus is on 26 grafts in the dHOPE arm. During perfusion, perfusate was sampled every 30 minutes for lactate, oxygen, and flavin mononucleotide (FMN) measurements-up.
Participants
Total Randomized Trial: 102 patients (26 allocated to dHOPE, 76 to standard cold storage), all receiving donor-after-brain-death (DBD) liver grafts. dHOPE Cohort Analyzed: 26 adult recipients meeting inclusion criteria (≥18 years old, informed consent). Median donor age was 53 years, and median recipient MELD was 12.
Outcomes
Primary Outcome: Predictive value of perfusate lactate (and FMN) for Early Allograft Dysfunction (EAD) – a standard measure of post-transplant graft function. Secondary Outcomes:Correlation of perfusate biomarkers with post-transplant hospital and ICU stay, peak liver enzymes, post-transplant complications (e.g., Clavien-Dindo grade ≥3 events), and other composite clinical scores (MEAF, L-GrAFT7).
Follow-up
1 year posttransplantation
CET Conclusions
The authors present analysis of a cohort of 26 patients within a single-centre RCT, the 26 patients received dHOPE and the control arm had standard care of SCS. The perfusate lactate during hypothermic preservation is utilised as a possible biomarker for transplant outcomes. Lactate assessment is feasible given it can be measured on a standard blood gas anayser, making it a quick and cheap biomarker compared with FMN, which requires a spectrofluorometer. Within the 26 patients they found lactate concentration in the perfusate after 120 minutes of dHOPE (≥3.45 mmol/L) predicted a significantly higher rate of EAD (67% vs. 6% below that threshold) and that elevated perfusate lactate correlated with longer hospital stays and higher peak transaminases, aligning with more severe graft dysfunction. Comparing lactate utility with FMN, which measured at 30 minutes also had predictive utility (AUC ~0.83). It seems lactate best discriminated EAD after a longer perfusion (2 hours), presumably reflecting time-dependent metabolic changes. The study is limited by small sample size (n=26 in dHOPE) and primarily DBD donors with relatively low-risk characteristics, which for a UK recipient cohort is less translatable. In the centres which use end-ischemic HOPE, it typically starts when the transplant is already in progress, so perfusate-based decisions to accept/reject might be limited. The absolute lactate level could be confounded by large graft weight, making delta-lactate (accumulation over 2 hours) potentially more informative. Finally, methodologically there was no formal blinding described, but objective biomarker endpoints reduce detection bias. Overall, while a secondary analysis of a relatively small single-centre randomized study, it was prospective with clearly defined endpoints and a structured HOPE protocol. Their findings reinforce that real-time lactate during HOPE could help gauge graft quality, complementing or substituting more complex measurements (e.g., FMN). This concept should be taken forward into a future multicentre validation, especially in broader donor populations (e.g., DCD, more steatotic grafts) and with extended HOPE. In a device to donor setting this may provide timing predictive information to influence clinical decision making.
Trial registration
ClinicalTrials.gov - NCT04812054