Jana Koustav, Rammohan Ashwin, Ramani Avinash, Gunasekaran Bhavani, Vij Mukul, Ramamoorthi Maharani, Jayakanthan Nivethitha, Kaliamoorthy Ilankumaran, Ramani Agragesh, Rela Mohamed
The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, Bharath Institute of Higher Education & Research, Chennai, India.
Acrannolife Genomics Private Limited, Chennai, India.
J Clin Exp Hepatol. 2024 Nov-Dec;14(6):101477. doi: 10.1016/j.jceh.2024.101477. Epub 2024 Jul 6.
BACKGROUND/AIMS: Predicting allograft dysfunction prior to clinical or biochemical evidence remains one of the challenges in transplantation, and a preclinical detection and early management of its cause allows for improved post-transplant outcomes. Donor-derived cell-free DNA (ddcfDNA) has been proposed as an important biomarker of allograft injury and has shown to predict dysfunction prior to any biochemical derangements. We aimed to investigate the diagnostic performance of ddcfDNA in detecting and differentiating the causes of early pre-biochemical detection of graft injury and in predicting the short-term outcomes of graft health using a patented protocol and proprietary set of single-nucleotide polymorphisms.
Blood samples were collected on defined postoperative days (1, 3, 7, and at 3 months) and were analysed through relatively economical patented protocol (Trunome™). Biopsy, biochemical tests, and clinical criteria were analysed between various subgroups.
Of a total 50 patients, percentage ddcfDNA (%ddcfDNA) levels were significantly elevated in the rejection group (n = 8) as compared to that in the non-rejection group (n = 42; median elevation: 12.8% vs 4.3%, respectively), with a significant correlation (r = 0.92, < 0.0001). Area under the receiver operating characteristic curve (AUC-ROC) analysis revealed that the %ddcfDNA levels can predict graft health more precisely than the conventional liver function tests (AUC for %ddcfDNA: 0.86; < 0.001; AUC for aspartate transaminase 0.65, = 0.08; AUC for alanine transaminase: 0.75, < 0.01). Moreover, %ddcfDNA levels (with a threshold of >10.2%) on post-operative day 7 accurately predicted short-term (3 months) health status of the graft with 93.33% sensitivity, 94.44% specificity, 87.50% positive predictive value, 97.14% negative predictive value, and 94.12% accuracy.
A single-timepoint ddcfDNA on postoperative day 7 accurately predicts graft health and improves risk stratification in the short-term.
背景/目的：在临床或生化证据出现之前预测同种异体移植功能障碍仍然是移植领域的挑战之一，对其病因进行临床前检测和早期管理有助于改善移植后的结局。供体来源的游离DNA（ddcfDNA）已被提出作为同种异体移植损伤的重要生物标志物，并已显示出在任何生化紊乱之前预测功能障碍的能力。我们旨在使用专利方案和一组专有的单核苷酸多态性来研究ddcfDNA在检测和区分移植损伤早期生化前检测的原因以及预测移植健康短期结局方面的诊断性能。
在术后特定天数（第1、3、7天和3个月时）采集血样，并通过相对经济的专利方案（Trunome™）进行分析。对各个亚组之间的活检、生化测试和临床标准进行分析。
在总共50例患者中，与非排斥组（n = 42；中位升高分别为12.8%对4.3%）相比，排斥组（n = 8）的ddcfDNA百分比（%ddcfDNA）水平显著升高，具有显著相关性（r = 0.92，<0.0001）。受试者工作特征曲线下面积（AUC-ROC）分析显示，%ddcfDNA水平比传统肝功能测试更能准确预测移植健康（%ddcfDNA的AUC：0.86；<0.001；天冬氨酸转氨酶的AUC：0.65，= 0.08；丙氨酸转氨酶的AUC：0.75，<0.01）。此外，术后第7天的%ddcfDNA水平（阈值>10.2%）以93.33%的敏感性、94.44%的特异性、87.50%的阳性预测值、97.14%的阴性预测值和94.12%的准确性准确预测了移植的短期（3个月）健康状况。
术后第7天的单次ddcfDNA能准确预测移植健康，并改善短期风险分层。
