Tsai Hsin-I, Lo Chi-Jen, Lee Chao-Wei, Lin Jr-Rung, Lee Wei-Chen, Ho Hung-Yao, Tsai Chia-Yi, Cheng Mei-Ling, Yu Huang-Ping
Department of Anesthesiology, Chang Gung Memorial Hospital Taoyuan 333, Taiwan.
College of Medicine, Chang Gung University Taoyuan 333, Taiwan.
Am J Transl Res. 2021 Jan 15;13(1):372-382. eCollection 2021.
Early allograft dysfunction (EAD) is associated with graft failure and mortality after living donor liver transplantation (LDLT). In this study, we report biomarkers superior to other conventional clinical markers in the prediction of EAD and all-cause in-hospital mortality in LDLT patient cohort. Blood samples of living donor liver transplant recipients were collected on postoperative day 1 and analyzed by liquid chromatography coupled with mass spectrometry (LC-MS). Significant metabolites associated with the prediction of EAD were identified using orthogonal projection to latent structures-discriminant analysis (OPLS-DA). A few lipids, more specifically, lysoPC (16:0), PC (18:0/20:5), betaine and palmitic acid (C16:0) were found to effectively differentiate EAD from non-EAD on postoperative day 1. A combination of these four metabolites showed an AUC of 0.821, which was further improved to 0.846 by the addition of a clinical parameter, total bilirubin. The panel exhibits a high prognostic accuracy in prediction of all-cause in-hospital mortality and mortality within 7 postoperative days with AUCs of 0.843 and 0.954. These results show the combination of metabolomics-derived biomarkers and clinical parameters demonstrates the power of panels in diagnostic and prognostic evaluation of LDLT.
早期移植物功能障碍(EAD)与活体肝移植(LDLT)后的移植物衰竭及死亡率相关。在本研究中,我们报告了在预测LDLT患者队列中的EAD及全因院内死亡率方面优于其他传统临床标志物的生物标志物。在术后第1天采集活体肝移植受者的血样,并通过液相色谱-质谱联用(LC-MS)进行分析。使用正交投影到潜在结构判别分析(OPLS-DA)确定与EAD预测相关的显著代谢物。发现一些脂质,更具体地说是溶血磷脂酰胆碱(16:0)、磷脂酰胆碱(18:0/20:5)、甜菜碱和棕榈酸(C16:0)在术后第1天能有效区分EAD与非EAD。这四种代谢物的组合显示曲线下面积(AUC)为0.821,通过加入临床参数总胆红素,该值进一步提高到0.846。该指标在预测全因院内死亡率及术后7天内死亡率方面具有较高的预后准确性,AUC分别为0.843和0.954。这些结果表明,代谢组学衍生的生物标志物与临床参数的组合证明了该指标在LDLT诊断和预后评估中的作用。