Abstract 10563: Differences in Donor-Derived Cell-Free DNA Levels During Allograft Rejections in Hepatitis C Positive Donor Recipient Heart Transplant Patients

Introduction: Non-invasive quantification of donor-derived cell-free DNA (dd-cfDNA) has recently been shown to correlate with endomyocardial biopsy (EMB) for diagnosis of allograft rejection in heart transplant (HTx) patients. Hepatitis C virus-positive (HCV+) donor hearts are being more utilized with comparable survival outcomes. Hypothesis: The aim of this study is to evaluate the utility of dd-cfDNA monitoring in different types of rejections in recipients of HCV+ donor hearts. Methods: We performed a retrospective review of recipients of HCV+ donor hearts between 2018-2022 with paired dd-cfDNA/GEP and EMB results. The levels of dd-cfDNA/GEP were compared in different rejection types and no rejection for patients using non-parametric comparison. CMR ISHLT ≥ Grade 2R and AMR ≥ Grade 1 from histology were considered as allograft rejection. Results: There were 17 patients who underwent heart transplant from HCV+ donor heart. There was a total of 89 paired samples with dd-cfDNA and EMB. The reason for the biopsy was mostly for routine surveillance (N=68, 76.4%). There was a total of 1 case (1.1%) of grade 2 CMR and 16 cases of pAMR (18%; 10 cases of grade 1, 6 cases of grade 2). Levels of dd-cfDNA were elevated in cases of AMR when compared to no rejection (Median: 0.24% vs. 0.12%, respectively, P<0.001; Figure 1A). There were 57 samples (78%) with dd-cfDNA reference values of <0.12%. In patients with no rejection, dd-cfDNA levels were all below 0.25%. The AUC for elevation of dd-cfDNA and allograft rejection was 0.85 [95% C.I.: 0.72-0.97; P<0.001; Figure 1B]. Conclusions: Non-invasive quantitation of dd-cfDNA levels is elevated in allograft rejection as assessed by traditional microscopy from EMB. There was no false-positive rate of dd-cfDNA in allograft rejection at a threshold of 0.25%. Further studies are indicated to study whether dd-cfDNA levels transiently increase only in the setting of allograft rejection or active hepatitis C viremia at the time of biopsy.