Donor-derived Cell-free DNA Distinguishes Acute Rejection from Other Causes of Graft Injury in Liver Transplant Recipients
1Gastroenterology & Hepatology
Comprehensive Transplant Center, Northwestern University, Chicago, IL, 2Viracor Eurofins, Lees Summit, MO, 3University of Arizona College of Medicine Tucson, Tucson, AZ
Meeting: 2021 American Transplant Congress
Abstract number: 199
Keywords: Genomics, Graft function, Liver transplantation, Rejection
Topic: Clinical Science » Liver » Liver: Immunosuppression and Rejection
Session Information
Session Time: 10:30am-11:30am
Presentation Time: 10:50am-11:00am
Location: Virtual
*Purpose: The donor derived cell-free DNA (ddcfDNA) has emerged as strong biomarker for allograft injury, where the fraction of ddcfDNA is reported to increase in allograft rejection. Compared to other organ transplants, the fraction of donor-derived cell-free DNA (dd-cfDNA) in blood has not been tested robustly as an acute rejection (AR) biomarker in liver transplant recipients (LTR). Our aim was to evaluate the ability of dd-cfDNA to distinguish AR from other causes (ADNR – acute dysfunction no rejection) at the time of graft dysfunction.
*Methods: Plasma tubes collected and stored from two LT biorepository cohorts (Northwestern University (NU); multicenter NIAID CTOT-14) were analyzed for ddcfDNA quantification. Patient phenotypes included AR (N=57), ADNR (N=68), control LT recipients with normal graft function (TX; N=94), as well as non-AR (combination of ADNR+TX; N=162). The sample set was randomly divided into discovery (70%, 153 samples) and validation (30%, 66 samples) sets, which were subsequently used to find and validate the optimal ddcfDNA cutoff, respectively.
*Results: We have tested and validated the application of ddcfDNA fraction as a biomarker of liver graft injury in clinically relevant comparisons (AR vs. TX, AR vs. non-AR, AR vs. ADNR) (Table)
| Clinical Groups | Optimal ddcfDNA in % (discovery) | Sensitivity(discovery) | Specificity (discovery) | AUC (discovery) | Sensitivity (validation) | Specificity (validation) | PPV/NPV(validation) |
| AR vs. TX | 5.3 | 95 (83-99) | 77(64-86) | 0.95(0.92-0.99) | 100(79-100) | 81(63-93) | 62/100(38-86)/(88-100) |
| AR vs. non-AR | 15.0 | 76(66-88) | 79(70-86) | 0.85(0.78-0.91) | 88(62-98) | 80(66-90) | 59/95(33-80)/(83-99) |
| AR vs. ADNR | 20.4 | 68(52-82) | 67(52-80) | 0.70(0.61-0.80) | 75(48-93) | 60(36-81) | 38/88(17-64)/(65-99) |
*Conclusions: dd-cfDNA can distinguish AR from other causes of liver graft dysfunction using optimal cut-off fractions. Given the high NPV (“rule out” AR test), prospective studies are needed to evaluate its utility in clinical practice in reducing invasive liver biopsies performed to exclude rejection.
To cite this abstract in AMA style:
Levitsky J, Miller M, Sinha R, Bixler E, Al-Turck A, Weems J, Altrich M, Kleiboeker S, Abecassis M. Donor-derived Cell-free DNA Distinguishes Acute Rejection from Other Causes of Graft Injury in Liver Transplant Recipients [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-distinguishes-acute-rejection-from-other-causes-of-graft-injury-in-liver-transplant-recipients/. Accessed November 24, 2024.« Back to 2021 American Transplant Congress