Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients
Dong Zhao, Tao Zhou, Yi Luo, Cheng Wu, Dongwei Xu, Chengpeng Zhong, Wen‐Ming Cong, Qiang Liu, Jianjun Zhang, Qiang Xia
Abstract
Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to biopsy. Of these, 11 (22.4%) patients were found to have rejection by biopsy. Dd-cfDNA levels were higher among patients with rejection compared to those with no rejection. In subgroup analysis, dd-cfDNA% among patients with rejection differed from those with EBV/CMV infection and DILI patients. Similarly, observations were available concerning dd-cfDNA (cp/mL). The AUC for dd-cfDNA% and dd-cfDNA (cp/mL) were 0.878, 0.841, respectively, both of which were higher than conventional LFTs. For rejection, dd-cfDNA% ≥ 28.7% yielded a sensitivity of 72.7%, specificity 94.7% and dd-cfDNA (cp/mL) ≥ 2076 cp/mL, yielded a sensitivity of 81.8%, specificity 81.9%. Of note, the dd-cfDNA distribution was significantly different between whole liver and LLS transplantation. In the setting of pediatric LTx, dd-cfDNA appears to be a sensitive biomarker indicating the presence of rejection.International Clinical Trails Registry Platform: ChiCTR1900022406.