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. The ROC-curve analysis identified an FMN level cutoff 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 of 0.858 (95% CI: 0.754-0.963, P <0.001), outperforming the donor risk index (area under the curve: 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 1-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. The 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].

Conclusions: 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.

Keywords: flavin mononucleotide; liver graft survival; liver transplantation; mitochondrial biomarkers; static cold storage; viability assessment.