Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction
Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction
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DOI：
10.1016/j.jhep.2014.04.023
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发表时间：
2014-09-01
影响因子：
25.7
通讯作者：
Lahoz, Agustin
中科院分区：
文献类型：
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作者：
Cortes, Miriam;Pareja, Eugenia;Lahoz, Agustin
背景和目标：原位肝移植术后早期移植物功能障碍（EAD）严重影响移植物和患者的预后，其发生率在很大程度上取决于供肝质量。然而，客观的生物标志物，可以评估移植质量和预测器官功能，仍然缺乏。本研究旨在探讨是否有术前供体肝代谢生物签名与EAD.Methods：一个全面的代谢分析124供体肝活检移植前收集的质谱联用液相色谱法进行。供体肝移植分为两组：显示EAD和即时移植功能（IGF）。多变量数据分析被用来搜索之间的关系存在于供体肝脏移植前和他们的功能recipies.Results：一组肝移植功能障碍相关的生物标志物。关键变化包括胆汁酸、溶血磷脂、磷脂、鞘磷脂和组氨酸代谢产物水平显著升高，均提示脂质稳态破坏和组氨酸途径改变。基于这些生物标志物，建立了预测EAD模型，并通过评估24个独立供体肝脏进行了进一步评估，灵敏度为91%，特异性为82%。该模型也成功地挑战了评估供体肝脏显示原发性非功能（n = 4）。结论：代谢组学生物签名，准确区分供体肝脏，后来显示EAD或IGF，已被破译。供肝在移植前代谢组学的显著差异可能与供肝质量的差异有关。拟议的代谢组学方法可能成为一种临床工具，供肝质量评估和移植前预测移植功能。(C)2014年欧洲肝脏研究协会。由Elsevier B出版。V.保留所有权利。
Background & Aims: Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD.Methods: A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients.Results: A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary nonfunction (n = 4).Conclusions: A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.