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Title: The Measurement of Donor-Specific Cell-Free DNA Identifies Recipients With Biopsy-Proven Acute Rejection Requiring Treatment After Liver Transplantation.
Austin Authors: Goh, Su Kah ;Do, Hongdo;Testro, Adam G ;Pavlovic, Julie ;Vago, Angela ;Lokan, Julie ;Jones, Robert M ;Christophi, Christopher ;Dobrovic, Alexander ;Muralidharan, Vijayaragavan 
Affiliation: Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia
Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia
Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia
Department of Surgery, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia
Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia
Hepato-Pancreato-Biliary & Transplant Surgery Unit, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Jul-2019 2019-06-21
Publication information: Transplantation direct 2019; 5(7): e462
Abstract: Assessment of donor-specific cell-free DNA (dscfDNA) in the recipient is emerging as a noninvasive biomarker of organ rejection after transplantation. We previously developed a digital polymerase chain reaction (PCR)-based approach that readily measures dscfDNA within clinically relevant turnaround times. Using this approach, we characterized the dynamics and evaluated the clinical utility of dscfDNA after liver transplantation (LT). Deletion/insertion polymorphisms were used to distinguish donor-specific DNA from recipient-specific DNA. Posttransplant dscfDNA was measured in the plasma of the recipients. In the longitudinal cohort, dscfDNA was serially measured at days 3, 7, 14, 28, and 42 in 20 recipients. In the cross-sectional cohort, dscfDNA was measured in 4 clinically stable recipients (>1-y posttransplant) and 16 recipients (>1-mo posttransplant) who were undergoing liver biopsies. Recipients who underwent LT without complications demonstrated an exponential decline in dscfDNA. Median levels at days 3, 7, 14, 28, and 42 were 1936, 1015, 247, 90, and 66 copies/mL, respectively. dscfDNA was higher in recipients with treated biopsy-proven acute rejection (tBPAR) when compared to those without. The area under the receiver operator characteristic curve of dscfDNA was higher than that of routine liver function tests for tBPAR (dscfDNA: 98.8% with 95% confidence interval, 95.8%-100%; alanine aminotransferase: 85.7%; alkaline phosphatase: 66.4%; gamma-glutamyl transferase: 80.1%; and bilirubin: 35.4%). dscfDNA as measured by probe-free droplet digital PCR methodology was reflective of organ health after LT. Our findings demonstrate the potential utility of dscfDNA as a diagnostic tool of tBPAR.
DOI: 10.1097/TXD.0000000000000902
ORCID: 0000-0002-6684-2521
PubMed URL: 31334336
ISSN: 2373-8731
Type: Journal Article
Appears in Collections:Journal articles

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