Protective effects of hypothermic oxygenated machine perfusion on bile composition after liver transplantation – findings from a randomized controlled trial

F Schliephake; D Uluk; I Lurje; Z Czigany; J Eden; J Pein; P Husen; U P Neumann; C Engelmann; M Kohlhepp; P Strnad; C Michalski; P Dutkowski; F Tacke; D Meierhofer; G Lurje

doi:10.1055/s-0045-1810645

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2025; 63(08): e374-e375
DOI: 10.1055/s-0045-1810645

Abstracts | DGVS/DGAV

Freie Vorträge

Protective effects of hypothermic oxygenated machine perfusion on bile composition after liver transplantation – findings from a randomized controlled trial

Authors

F Schliephake

¹Charité – Universitätsmedizin Berlin, Department of Surgery, Berlin, Deutschland

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland
D Uluk

¹Charité – Universitätsmedizin Berlin, Department of Surgery, Berlin, Deutschland

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland
I Lurje

³Charité – Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum,, Berlin, Deutschland

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland
Z Czigany

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland

⁴University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Deutschland
J Eden

⁵University of Groningen, Department of Surgery, Section of HPB Surgery and Liver Transplantation, Groningen, Niederlande
J Pein

¹Charité – Universitätsmedizin Berlin, Department of Surgery, Berlin, Deutschland
P Husen

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland
U P Neumann

⁴University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Deutschland
C Engelmann

³Charité – Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum,, Berlin, Deutschland
M Kohlhepp

³Charité – Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum,, Berlin, Deutschland
P Strnad

⁶University Hospital RWTH Aachen, Department of Internal Medicine III, Aachen, Deutschland
C Michalski

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland
P Dutkowski

⁷Department of Surgery, University Hospital Basel, Basel, Schweiz
F Tacke

³Charité – Universitätsmedizin Berlin, Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum,, Berlin, Deutschland

⁶University Hospital RWTH Aachen, Department of Internal Medicine III, Aachen, Deutschland
D Meierhofer

⁸Max Planck Institute for Molecular Genetics, Berlin, Deutschland
G Lurje

¹Charité – Universitätsmedizin Berlin, Department of Surgery, Berlin, Deutschland

²Heidelberg University Hospital, Department of General-, Visceral- and Transplantation Surgery, Heidelberg, Deutschland

⁴University Hospital RWTH Aachen, Department of Surgery and Transplantation, Aachen, Deutschland

Abstract

Full Text

Background and aims: In liver transplantation, bile acid toxicity is associated with damage to both hepatocytes and cholangiocytes. End-ischemic hypothermic oxygenated machine perfusion (HOPE) mitigates ischemia-reperfusion injury (IRI) and prevents biliary damage. However, its impact on bile composition remains unclear, as bile samples are typically unavailable after transplantation, resulting in a lack of evidence ([Abb. 1] [2] [3]).

Abb. 1

Abb. 2

Abb. 3

Methods: Bile was collected within three days post-liver transplantation in a multicentric randomized controlled trial (NCT03124641), from 26 patients receiving extended criteria donation (ECD) allografts from donors after brain death (DBD). Fourteen donor livers were static cold stored (SCS group), while 12 livers underwent end-ischemic HOPE after cold storage (HOPE group). Bile composition and metabolic parameters were analyzed with mass spectrometry. Expression of bile transporters and enzymes was assessed in liver biopsies before and after transplantation.

Results: Hydrophobic BAs were positively correlated with IRI severity, such as serum ASAT and ALAT, and decreased postoperatively for all allografts (POD-1 vs. POD-2/POD-3 both p<0.001). Expression of the hepatocyte bile transporters ABCB4 and ABCG8 decreased after reperfusion (p=0.045; p<0.001). The HOPE-group had higher total-and primary bile acid (BA) levels on postoperative day (POD)-3 compared to cold stored livers (p=0.047, p=0.027) and a significant increase in the fraction of primary BAs from POD-1 to POD-3 (p=0.005). HOPE-treated organs exhibited an increase in phosphatidylcholine and phosphatidylethanolamine levels leading to higher phospholipid levels on POD-3 compared to the SCS group (p=0.043) and a decline in BA/PC ratio.

Conclusion: This is the first randomized study demonstrating effects of HOPE treatment on bile lipid secretion and bile composition following ECD-DBD liver transplantation. Protection from bile toxicity may represent a novel mechanism underlying the effects of HOPE.

Abstracts

Präsentiert in der Sitzung: Kontroversen und Grenzen der Lebertransplantation

Donnerstag, 18. September 2025, 16:30 – 18:00, MZF 4

Figures

Abb. 1

Abb. 2

Abb. 3