Machine Perfusion or Straight to Transplant? Predictive Value of Flavin Mononucleotide Levels in Flush Solution of Human Liver Allograft

Abstract

Objective: This study examined the predictive value of Flavin Mononucleotide (FMN) levels in the flush solution used during cold storage of donor livers on outcomes post-transplantation.

Background: Static cold storage for liver grafts induces hypoxia with subsequent impaired mitochondrial function and Flavin Mononucleotide (FMN) release upon reperfusion.

Methods: This study enrolled 62 recipients who received whole liver grafts from donation after brain death (n=50) and circulatory death donors (n=12) between June 2022 and July 2023. FMN concentrations were measured in flush solutions on the back-table. ROC-curve analysis identified an FMN level cut-off for graft survival. Post-transplant outcomes were examined according to FMN levels.

Results: FMN level was significantly associated with graft survival, with an area-under-the-curve (AUC) of 0.858 (95%CI: 0.754-0.963, P<0.001), outperforming the donor risk index (AUC 0.571, 95%CI: 0.227-0.915, P=0.686). The study cohort was divided into low-FMN (<37.5 ng/mL, n=40) and high-FMN groups (≥37.5 ng/mL, n=22). The low-FMN group had superior one-year graft survival compared with the high-FMN group (100% vs. 77%, P=0.003). Levels of transaminases within 7 days post-transplant were significantly higher in the high-FMN group (P=0.003). The high-FMN group developed acute rejections (41% vs. 15%, P=0.023) and early allograft dysfunction (50% vs. 20%, P=0.014) more frequently. Median comprehensive complication index in the high-FMN group was significantly higher (54 [interquartile range, 40-78] vs. 42 [interquartile range, 28-52], P=0.017).

Conclusion: The FMN level measured in donor livers' cold storage flush solution is a valid biomarker to predict post-transplant outcomes. Liver grafts with high FMN levels may benefit from machine perfusion to improve outcomes.