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.

中文翻译：

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机器灌注还是直接移植？黄素单核苷酸水平在人肝同种异体移植物冲洗液中的预测价值。


目的 本研究检查了供体肝脏冷藏期间使用的冲洗液中黄素单核苷酸 （FMN） 水平对移植后结局的预测价值。背景 肝移植物的静态冷藏会诱导缺氧，随后线粒体功能受损，再灌注时黄素单核苷酸 （FMN） 释放。方法 本研究招募了 62 名在 2022 年 6 月至 2023 年 7 月期间接受脑死亡后捐献全肝移植物 （n=50） 和循环死亡供体 （n=12） 的受者。在后台的冲洗溶液中测量 FMN 浓度。ROC 曲线分析确定了移植物存活的 FMN 水平临界值。根据 FMN 水平检查移植后结局。结果 FMN 水平与移植物存活率显著相关，曲线下面积 （AUC） 为 0.858 （95%CI： 0.754-0.963，P<0.001），优于供者风险指数 （AUC 0.571,95%CI： 0.227-0.915，P=0.686）。研究队列分为低 FMN 组 （<37.5 ng/mL， n=40） 和高 FMN 组 （≥37.5 ng/mL， n=22）。与高 FMN 组相比，低 FMN 组的 1 年移植物存活率更高 （100% vs. 77%，P = 0.003）。高 FMN 组移植后 7 天内转氨酶水平显著升高 （P=0.003）。高 FMN 组发生急性排斥反应 （41% vs. 15%，P=0.023） 和早期同种异体移植物功能障碍 （50% vs. 20%，P=0.014） 更频繁。高 FMN 组的综合并发症指数中位数显著升高 （54 [四分位距，40-78] vs. 42 [四分位距，28-52]，P = 0.017）。结论 供体肝脏冷藏冲洗液中测得的 FMN 水平是预测移植后结果的有效生物标志物。 FMN 水平高的肝移植物可能受益于机器灌注以改善结局。