Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Department of Surgery, University of Cambridge, Cambridge, UK.
Br J Surg. 2024 Jun 12;111(6). doi: 10.1093/bjs/znae084.
Biomarkers with strong predictive capacity towards transplantation outcome for livers undergoing normothermic machine perfusion (NMP) are needed. We investigated lactate clearing capacity as a basic function of liver viability during the first 6 h of NMP.
A trial conducted in 6 high-volume transplant centres in Europe. All centres applied a back-to-base NMP approach with the OrganOx metra system. Perfusate lactate levels at start, 1, 2, 4 and 6 h of NMP were assessed individually and as area under the curve (AUC) and correlated with EAD (early allograft dysfunction), MEAF (model for early allograft function) and modified L-GrAFT (liver graft assessment following transplantation) scores.
A total of 509 livers underwent ≥6 h of NMP before transplantation in 6 centres in the UK, Germany and Austria. The donor age was 53 (40-63) years (median, i.q.r.).The total NMP time was 10.8 (7.9-15.7) h. EAD occurred in 26%, MEAF was 4.72 (3.54-6.05) and L-GrAFT10 -0.96 (-1.52--0.32). Lactate at 1, 2 and 6 h correlated with increasing robustness with MEAF. Rather than a binary assessment with a cut-off value at 2 h, the actual 2 h lactate level correlated with the MEAF (P = 0.0306 versus P = 0.0002, Pearson r = 0.01087 versus r = 0.1734). The absolute lactate concentration at 6 h, the AUC of 0-6 h and 1-6 h (P < 0.0001, r = 0.3176) were the strongest predictors of MEAF.
Lactate measured 1-6 h and lactate levels at 6 h correlate strongly with risk of liver allograft dysfunction upon transplantation. The robustness of predicting MEAF by lactate increases with perfusion duration. Monitoring lactate levels should be extended to at least 6 h of NMP routinely to improve clinical outcome.
需要寻找具有较强预测能力的生物标志物，以评估行常温机器灌注（NMP）的肝脏移植的结果。本研究旨在探讨在 NMP 的最初 6 小时内，肝脏活力的基本功能（即乳酸清除能力）。
该试验在欧洲的 6 个大容量移植中心进行。所有中心均采用基于 OrganOx metra 系统的常规 NMP 方法。分别评估 NMP 开始时、1 小时、2 小时、4 小时和 6 小时的灌注液中乳酸水平，并计算其曲线下面积（AUC），同时评估其与早期移植物功能障碍（EAD）、早期移植物功能模型（MEAF）和改良 L-GrAFT（移植后肝脏评估）评分的相关性。
英国、德国和奥地利的 6 个中心共有 509 例肝脏接受了≥6 小时的 NMP 灌注，然后进行移植。供体年龄为 53（40-63）岁（中位数，四分位间距）。总 NMP 时间为 10.8（7.9-15.7）小时。26%的患者发生 EAD，MEAF 为 4.72（3.54-6.05），L-GrAFT10 为-0.96（-1.52--0.32）。1 小时、2 小时和 6 小时时的乳酸与 MEAF 的稳健性呈正相关。与 2 小时时的截值二分法评估相比，实际的 2 小时乳酸水平与 MEAF 呈正相关（P = 0.0306 与 P = 0.0002，Pearson r = 0.01087 与 r = 0.1734）。6 小时时的绝对乳酸浓度、0-6 小时时的 AUC 和 1-6 小时时的 AUC（P < 0.0001，r = 0.3176）是 MEAF 的最强预测因子。
移植后肝脏功能障碍的风险与 1-6 小时时的乳酸测量值和 6 小时时的乳酸水平密切相关。乳酸对 MEAF 的预测稳健性随着灌注时间的延长而增加。为了改善临床结果，应常规将乳酸监测延长至至少 6 小时的 NMP。
