Meszaros Andras T, Weissenbacher Annemarie, Schartner Melanie, Egelseer-Bruendl Tim, Hermann Martin, Unterweger Jasmin, Mittelberger Christa, Reyer Beatrix A, Hofmann Julia, Zelger Bettina G, Hautz Theresa, Resch Thomas, Margreiter Christian, Maglione Manuel, Komlódi Timea, Ulmer Hanno, Cardini Benno, Troppmair Jakob, Öfner Dietmar, Gnaiger Erich, Schneeberger Stefan, Oberhuber Rupert
Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria.
Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria.
Transpl Int. 2024 Feb 23;37:12380. doi: 10.3389/ti.2024.12380. eCollection 2024.
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 - control efficiency, calculated as 1-/ from the capacity of oxidative phosphorylation and non-phosphorylating respiration . 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; = 0.01), indicating decreased cell viability. - control efficiency was predictive of EAD (0.76 ± 0.06 in IF vs. 0.70 ± 0.08 in EAD-livers; = 0.02) and correlated with the RTCA score. Both RTCA and - 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.
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肝移植结果的预测能力。我们纳入了43例连续接受肝移植的患者。对静态冷藏后到达时采集的肝活检样本进行组织学、实时共聚焦成像分析（RTCA）和高分辨率呼吸测定法（HRR），以评估组织匀浆的线粒体呼吸。早期移植物功能障碍（EAD）作为主要终点。对HRR数据进行分析，重点关注ATP产生的效率或 - 控制效率，其计算方法为1 - （氧化磷酸化能力与非磷酸化呼吸能力之比）。22名受者出现了EAD。移植前组织学不能预测EAD。与未发生EAD的队列（0.70±2.08）相比，EAD队列的平均RTCA评分显著更低（-0.75±2.27；P = 0.01），表明细胞活力降低。 - 控制效率可预测EAD（未发生EAD的肝脏中为0.76±0.06，EAD肝脏中为0.70±0.08；P = 0.02），且与RTCA评分相关。冷藏期间采集的活检样本中的RTCA和 - 控制效率对肝移植结果均具有预测能力。因此，在肝移植中进行风险分层、活力评估和生物能量测试时，应考虑RTCA和HRR。
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