Hypothermic oxygenated and normothermic machine perfusion mitigate innate systemic and hepatic inflammation after liver transplantation
In brief
HOPE and normothermic perfusion reduce early neutrophil infiltration in liver grafts
In a randomized substudy of 47 liver transplant recipients, both hypothermic oxygenated perfusion (HOPE) and normothermic perfusion reduced neutrophil infiltration in donor livers during early reperfusion. HOPE also sped recovery of circulating lymphocyte counts and lowered blood neutrophils, while both approaches dampened inflammatory immune activity; whether these immune changes improve clinical outcomes remains unclear.
- Journal
- Gut (Q1)
- Published
- 29 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Isabella Lurje, Paul Horn, Adrien Guillot, Deniz Uluk, Frederik Schliephake, Luna Rohm, et al.
- PMID
- 42810848
- DOI
- 10.1136/gutjnl-2026-338907
Why clinicians should know about it
- Picked for Gastroenterology (top studies of the week, 4 October 2026): HOPE and NMP reduced neutrophil infiltration during early IRI
Abstract
BACKGROUND: Immune-mediated injury drives ischaemia-reperfusion injury (IRI) following liver transplantation. While hypothermic oxygenated (HOPE) and normothermic machine perfusion (NMP) improve clinical outcomes, their immunological effects in humans remain unclear. OBJECTIVE: To examine hepatic and systemic immune responses across preservation strategies in a randomised controlled clinical setting. DESIGN: In this mechanistic substudy of the HOPE-NMP randomised controlled trial (NCT04644744), we analysed immune responses in n=47 recipients of extended criteria donor livers from brain-dead donors randomised to static cold storage (SCS), end-ischaemic HOPE or end-ischaemic NMP. Liver biopsies were obtained at organ arrival and early IRI. Blood samples were collected preoperatively, during reperfusion and on postoperative days 1, 2, 3 and 7. METHODS: Analyses included spectral flow cytometry, multiplex immunofluorescence with spatial analyses, cytokine profiling, cellular bioenergetics and mass spectrometry. RESULTS: In human liver allografts, both HOPE and NMP reduced neutrophil infiltration during early IRI, without altering intrahepatic spatial distribution. Machine perfusion induced phenotypic modulation of graft-infiltrating myeloid cells, characterised by downregulation of pro-inflammatory and adhesion markers. Peripheral lymphocyte numbers, particularly of NK cells and T cells, normalised faster after HOPE, compared with SCS and NMP groups, correlating with reduced liver injury. Absolute and relative systemic neutrophil numbers were lower in HOPE-recipients. Machine perfusion decreased the inflammatory activation of circulating myeloid and innate lymphoid cells, while inhibitory immune checkpoints were upregulated postoperatively. CONCLUSIONS: In a randomised controlled trial using human samples, HOPE and NMP differentially modulate hepatic and systemic immune responses, attenuating neutrophil-driven inflammation and promoting immune regulation after liver transplantation.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.