Role of Donor-derived Cell-free DNA In Predicting Short-term Allograft Health In Liver Transplant Recipients

Abstract

BackgroundPredicting 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. MethodsBlood samples were collected on defined postoperative days (1-, 3-, 7- and at 3-months) and were analysed through relatively economical patented protocol (TrunomeTM). Biopsy, biochemical tests, and clinical criteria were analysed between various subgroups. ResultOf a total 50 patients, percentage ddcfDNA (%ddcfDNA) levels were significantly elevated in the rejection group (n=8) as compared to the non-rejection group (n= 42; median elevation 12.8% vs 4.3% respectively) with a significant correlation (r = 0.92, p<0.0001). AUC-ROC analysis revealed that the %ddcfDNA levels can predict graft health more precisely when compared to the conventional liver function tests (AUC for %ddcfDNA- 0.86; p<0.001; AUC for AST-0.65, p=0.08; AUC for ALT- 0.75, p<0.01). Moreover, %ddcfDNA levels (with a threshold >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. ConclusionA single time point ddcfDNA on postoperative day 7 accurately predicts graft health and improves risk stratification in the short-term.