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Abstract：
Donor organ biomarkers with sufficient predictive value in liver transplantation (LT) are lacking. We herein evaluate liver viability and mitochondrial bioenergetics for their predictive capacity towards the outcome in LT. We enrolled 43 consecutive patients undergoing LT. Liver biopsy samples taken upon arrival after static cold storage were assessed by histology, real-time confocal imaging analysis (RTCA), and high-resolution respirometry (HRR) for mitochondrial respiration of tissue homogenates. Early allograft dysfunction (EAD) served as primary endpoint. HRR data were analysed with a focus on the efficacy of ATP production or P-L control efficiency, calculated as 1-L/P from the capacity of oxidative phosphorylation P and non-phosphorylating respiration L. Twenty-two recipients experienced EAD. Pre-transplant histology was not predictive of EAD. The mean RTCA score was significantly lower in the EAD cohort (-0.75 ± 2.27) compared to the IF cohort (0.70 ± 2.08; p = 0.01), indicating decreased cell viability. P-L control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; p = 0.02) and correlated with the RTCA score. Both RTCA and P-L control efficiency in biopsy samples taken during cold storage have predictive capacity towards the outcome in LT. Therefore, RTCA and HRR should be considered for risk stratification, viability assessment, and bioenergetic testing in liver transplantation.
摘要：
在肝移植（LT）中缺乏具有足够预测价值的供体器官生物标志物。我们在此评估肝脏活力和线粒体生物能量学对LT结果的预测能力。我们招募了43例接受LT的连续患者。通过组织学评估静态冷藏后到达时采集的肝活检样本，实时共聚焦成像分析（RTCA），和组织匀浆线粒体呼吸的高分辨率呼吸测定（HRR）。早期同种异体移植功能障碍（EAD）是主要终点。分析了HRR数据，重点是ATP产生或P-L控制效率的功效，根据氧化磷酸化P和非磷酸化呼吸L的能力计算为1-L/P。22名接受者经历了EAD。移植前组织学不能预测EAD。EAD队列的平均RTCA评分（-0.75±2.27）明显低于IF队列（0.70±2.08；p=0.01），表明细胞活力降低。P-L控制效率可预测EAD（IF中的0.76±0.06与EAD肝脏为0.70±0.08；p=0.02），并与RTCA评分相关。在冷藏期间采集的活检样品中的RTCA和P-L控制效率都具有对LT结果的预测能力。因此,RTCA和HRR应考虑风险分层，可行性评估，和肝移植中的生物能量测试。
