Association of perfusate cytokine concentrations during liver graft ex situ normothermic perfusion to donor type and postoperative outcomes

The use of the so-called extended criteria donors increases the number of grafts available for transplantation. Many studies reported their good outcomes but their use is debated due to increased risk of complications. Ex situ liver perfusion has reduced graft discard rate and helped to test their function before implantation. Cytokines are known to be involved in ischemia-reperfusion injury, but their potential to predict liver function during normothermic machine perfusion (NMP) has not been fully investigated. The aim of this study was to compare cytokines levels during NMP in 3 different types of donors (donation after brain death, donation after circulatory death [DCD]-II, DCD-III) and correlate these data to postoperative clinical and biochemical outcomes. All donations after brain deaths older than 70 years and DCDs transplanted after NMP were included. IL-6, IL-10, and TNF were measured during NMP and correlated with clinical outcomes. Thirty liver grafts were transplanted after NMP: 16 donations after brain deaths, 7 DCD-II, and 7 DCD-III. There were 6 cases of early allograft dysfunction (20.0%), 10 of post-reperfusion syndrome (33.3%), and 11 cases of acute kidney injury (36.7%), with no major differences among groups. A positive correlation was found between perfusate IL-6 levels and the bilirubin peak within 7 days after liver transplantation, while IL-10 was associated with the intensive care unit stay and TNF to the international normalized ratio peak within 7 days. IL-6 was negatively associated with postoperative ALT levels and IL-10 to bilirubin peak. A correlation between higher IL-6 levels at 2 hours and graft loss was found. This is the first study to compare cytokines profile during NMP in 3 different types of donors and correlate it to clinical outcomes. A correlation between IL-6 concentration and graft failure was found. The role and significance of inflammatory markers in machine perfusion perfusate and their potential to assess graft viability and the risk of post-liver transplantation complications have to be further addressed.