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供体移植物低温氧合机器灌注期间内皮糖萼损伤标志物Syndecan-1有助于预测肝移植术后早期移植物功能障碍。

Endothelial glycocalyx damage marker syndecan-1 during hypothermic oxygenated machine perfusion of donor grafts facilitates prediction of early allograft dysfunction after liver transplantation.

作者信息

Rauter Laurin, Kollmann Dagmar, Schiefer Judith, Spasic Marija, Raeven Pierre, Dingfelder Jule, Pereyra David, Baron David M, Pompouridou Effimia, Soliman Thomas, Berlakovich Gabriela, Györi Georg

机构信息

Division of Transplantation, Department of General Surgery, Medical University of Vienna, Vienna, Austria.

Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria.

出版信息

Hepatobiliary Surg Nutr. 2025 Apr 1;14(2):233-245. doi: 10.21037/hbsn-24-33. Epub 2024 Aug 17.

DOI:10.21037/hbsn-24-33
PMID:40342764
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12057489/
Abstract

BACKGROUND

Ischemia reperfusion injury (IRI) is a major contributing factor to organ damage in liver transplantation (LT) impacting donor organ quality and patient survival. IRI-inflicted graft injury can be reduced by using hypothermic oxygenated machine perfusion (HOPE) as a preservation strategy instead of static cold storage (SCS). The endothelial glycocalyx is highly sensitive to IRI and its degradation during graft preservation and reperfusion was previously associated with inferior postoperative outcome after LT. Here, we aimed to measure glycocalyx degradation during and after HOPE in order to evaluate its potential for viability-assessment during machine perfusion and outcome prediction in patients undergoing LT.

METHODS

Glycocalyx degradation was quantified via enzyme-linked immunoassay (ELISA) for its main component syndecan-1 (Sdc-1) in serum of 40 patients undergoing LT after HOPE. In addition, Sdc-1 was evaluated at multiple time points during HOPE. Patients were followed up for 3.5 years to assess postoperative complications including morbidity, the development of early allograft dysfunction (EAD) and graft survival.

RESULTS

Liver grafts which later developed EAD showed significantly higher Sdc-1 concentrations after 60 min of HOPE compared to grafts exhibiting normal postoperative function (P=0.02). Receiver operating characteristic analysis revealed a strong predictive potential with an area under the curve of 0.73. A cut-off at 808 ng/mL Sdc-1 at 60 min of HOPE allowed identification of a high-risk group with an incidence of EAD of 66.7%. Sdc-1 concentrations increased during all types of HOPE but were significantly higher in HOPE versus dual HOPE (D-HOPE) after 120 min of perfusion (P=0.02).

CONCLUSIONS

Sdc-1 evaluated at 60 min during HOPE allows prediction of EAD after LT. Accordingly, Sdc-1 should be considered a potential additional biomarker for viability assessment during HOPE.

摘要

背景

缺血再灌注损伤(IRI)是肝移植(LT)中导致器官损伤的主要因素,影响供体器官质量和患者生存率。通过使用低温氧合机器灌注(HOPE)作为保存策略而非静态冷藏(SCS),可减轻IRI造成的移植物损伤。内皮糖萼对IRI高度敏感,其在移植物保存和再灌注过程中的降解先前与LT术后不良结局相关。在此,我们旨在测量HOPE期间及之后糖萼的降解情况,以评估其在机器灌注期间进行生存能力评估及预测LT患者结局的潜力。

方法

通过酶联免疫吸附测定(ELISA)对40例接受HOPE后进行LT的患者血清中糖萼的主要成分多配体蛋白聚糖-1(Sdc-1)进行定量分析。此外,在HOPE期间的多个时间点对Sdc-1进行评估。对患者进行3.5年的随访,以评估术后并发症,包括发病率、早期移植物功能障碍(EAD)的发生情况和移植物存活情况。

结果

与术后功能正常的移植物相比,后来发生EAD的肝移植物在HOPE 60分钟后Sdc-1浓度显著更高(P = 0.02)。受试者工作特征分析显示其具有较强的预测潜力,曲线下面积为0.73。HOPE 60分钟时Sdc-1浓度截断值为808 ng/mL时,可识别出EAD发生率为66.7%的高危组。在所有类型的HOPE过程中,Sdc- concentrations浓度均升高,但在灌注120分钟后,HOPE组的Sdc-1浓度显著高于双模式HOPE(D-HOPE)组(P = 0.02)。

结论

HOPE期间60分钟时评估的Sdc-1可预测LT术后的EAD。因此,Sdc-1应被视为HOPE期间进行生存能力评估的潜在附加生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ea/12057489/812fcad49017/hbsn-14-02-233-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ea/12057489/760bc52d38ce/hbsn-14-02-233-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ea/12057489/812fcad49017/hbsn-14-02-233-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ea/12057489/760bc52d38ce/hbsn-14-02-233-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02ea/12057489/812fcad49017/hbsn-14-02-233-f2.jpg

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Biliary Viability Assessment and Treatment Options of Biliary Injury During Normothermic Liver Perfusion-A Systematic Review.常温肝灌注期间胆道损伤的胆道活力评估和治疗选择——系统评价。
Transpl Int. 2022 May 30;35:10398. doi: 10.3389/ti.2022.10398. eCollection 2022.
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Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers.
序贯低温及常温机器灌注使高危供肝安全移植成为可能。
Am J Transplant. 2022 Jun;22(6):1658-1670. doi: 10.1111/ajt.17022. Epub 2022 Apr 18.
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The Endothelial Glycocalyx as a Double-Edged Sword in Microvascular Homeostasis and Pathogenesis.内皮糖萼在微血管稳态与发病机制中的双刃剑作用
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