MSACL 2019 EU Abstract

Analysis of Changes in Bile Acids Concentration in Bile in Response to the Degree of Liver Ischemia and the Method of Organ Preservation

Kamil Łuczykowski (1), Natalia Warmuzińska (1), Iga Stryjak (1), Dagmar Kollmann (2), Markus Selzner (2,3), Barbara Bojko (1)
(1) Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Nicolaus Copernicus University in Toruń, Collegium Medicum in Bydgoszcz, Poland (2) Multi Organ Transplant Program, Department of Surgery, Toronto General Hospital, University Health Network, Toronto, Canada (3) Department of Medicine, Toronto General Hospital, Toronto, Canada

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Kamil Łuczykowski (Presenter) Nicolaus Copernicus University in Toruń >> POSTER (PDF)

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

Introduction: Liver transplant surgery is currently the standard of treatment in patients with end-stage organ failure. Nowadays, the dominant method of organ preservation used by most transplantation centers is the static cold storage (SCS). However, a better method of organ preservation is sought, which would allow extending the storage time of the graft while maintaining its proper quality The proposed method is normothermic ex-vivo liver perfusion (NEVLP), based on maintaining normal metabolic activity, which gives the opportunity to better assessment of liver viability before implantation. One of the possibilities is to assess the production of bile by the liver perfused in these conditions. It is considered that the production of bile alone is not sufficient evidence for the proper functioning of the liver and directs the research to assess the composition of bile. Therefore, it is assumed that changes in the concentration of bile acids, which are the main component of bile, may correlate with changes occurring in the transplanted organ.

Methods: The study was performed on bile samples obtained from two types of porcine model donors: heart beating donor (HBD) and donor after cardiac death (DCD). Samples were collected during SCS and NEVLP at specific time points: before organ harvest, during perfusion (for NEVLP), reperfusion and the first few days after transplantation. The DCD group was divided due to the time of organ ischemia: 30’ for SCS and 30’, 60’, 90’ for NEVLP (n=3 in each group). Sample preparation was performed according to the thin-film solid phase microextraction (TF-SPME), using C18 sorbent as the extraction phase. Extracts were analyzed using the LC-MS platform with Nexera UHPLC system and a triple quadrupole mass spectrometer LC–MS 8060 (Shimadzu) equipped with an ESI source in the negative-ion mode working in the multiple reaction monitoring (MRM) mode.

Results: The conjugated forms of bile acids (with taurine or glycine) were significantly predominant in the bile samples compared to unconjugated forms. Changes in concentrations of individual bile acids depending on the method of preservation and the period of organ ischemia were observed. The high concentration of taurocholic acid is characteristic for the perfusion period (eg. 3793,64±255,5 vs. 1,81±0,45 ug/mL compared to SHAM for 30'DCD) and is still present in the reperfusion of the 90’DCD group. Furthermore, prolonged ischemia caused an increase in taurodeoxycholic (15.87±8.22 vs. 2.83±0.57 ug/mL) and glycodeoxycholic acid (135.82±78.5 vs. 18.56±4.57 ug/mL) levels in the first days after transplantation compared to HBD group.

Conclusions: TF-SPME is a high-throughput sample preparation method that can be effectively used for profiling bile samples. Changes in bile acid concentrations in bile samples may correlate with the metabolic processes occurring in the transplanted organ. Further research into the composition of bile may allow to find biomarkers of liver function.