Biliary Glutathione as a Potential Marker for Viability Assessment of Cholangiocytes During Normothermic Machine Perfusion of Livers.

Abstract

Background: Normothermic machine perfusion (NMP) is increasingly used to assess liver grafts before transplantation. While viability assessment of the hepatocellular compartment has been widely adopted, viability assessment of the biliary compartment remains controversial due to the lack of reliable markers. Glutathione (GSH) plays a key role in bile formation and may serve as a marker for biliary viability. Thus, the present study aimed to investigate the suitability of GSH as a potential marker for biliary viability assessment during NMP.

Methods: Between 2018 and 2021, livers undergoing NMP were included in the study. Bile samples were collected at 1 h, 6 h, and at the end of NMP, and then analyzed using enzyme-linked immunosorbent assay (ELISA). Results were correlated with perfusion parameters and clinical outcomes.

Results: 56 livers underwent NMP during the study period, of which 41 were successfully transplanted (73.2%). Within 1 year after transplantation, 19 patients (46.3%) developed biliary complications. 1-year patient survival was 80.5% and 1-year graft survival (death-censored) was 94.6%. The GSH in transplanted livers showed a significant increase over time (Hour 1: 25.9 ± 31.2 μM vs. End: 108.7 ± 95.3 μM, p < 0.001) and significant inverse correlation with the occurrence of biliary complications after transplantation (p < 0.05). GSH concentration at the first hour measurement was significantly lower in livers that were deemed non-transplantable (11.2 μM vs. 25.9 μM, p = 0.006).

Conclusions: Our data show an increase of GSH in bile during liver ex situ NMP. We found a negative correlation between GSH concentration and the development of biliary complications, suggesting GSH as a new marker for biliary viability assessment.