Graft-derived cell-free DNA, a noninvasive early rejection and graft damage marker in liver transplantation: A prospective, observational, multicenter cohort study

Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effecti...

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Bibliographic Details
Published in:PLoS medicine 2017-04, Vol.14 (4), p.e1002286
Main Authors: Schütz, Ekkehard, Fischer, Anna, Beck, Julia, Harden, Markus, Koch, Martina, Wuensch, Tilo, Stockmann, Martin, Nashan, Björn, Kollmar, Otto, Matthaei, Johannes, Kanzow, Philipp, Walson, Philip D, Brockmöller, Jürgen, Oellerich, Michael
Format: Article
Language:English
Subjects:
Adult
Aged
Analysis
Area Under Curve
Biology and Life Sciences
Biomarkers
Biomarkers - blood
Biopsy
Blood circulation
Chimerism
Cohort analysis
Deoxyribonucleic acid
DNA
DNA - blood
DNA methylation
Female
Genetic aspects
Genomes
Germany
Graft rejection
Graft Rejection - blood
Graft Rejection - diagnosis
Grafting
Health aspects
Hepacivirus
Humans
Immunology
Immunosuppression
Leukocytes - metabolism
Leukopenia
Liver
Liver Function Tests
Liver Transplantation
Liver transplants
Logistic Models
Male
Medicine and Health Sciences
Middle Aged
Open access publishing
Patients
Pharmacology
Plasma
Prospective Studies
ROC Curve
Single nucleotide polymorphisms
Surgery
Therapeutic drug monitoring
Transplants & implants
Viruses
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Summary:Graft-derived cell-free DNA (GcfDNA), which is released into the blood stream by necrotic and apoptotic cells, is a promising noninvasive organ integrity biomarker. In liver transplantation (LTx), neither conventional liver function tests (LTFs) nor immunosuppressive drug monitoring are very effective for rejection monitoring. We therefore hypothesized that the quantitative measurement of donor-derived cell-free DNA (cfDNA) would have independent value for the assessment of graft integrity, including damage from acute rejection. Traditional LFTs were performed and plasma GcfDNA was monitored in 115 adults post-LTx at three German transplant centers as part of a prospective, observational, multicenter cohort trial. GcfDNA percentage (graft cfDNA/total cfDNA) was measured using droplet digital PCR (ddPCR), based on a limited number of predefined single nucleotide polymorphisms, enabling same-day turn-around. The same method was used to quantify blood microchimerism. GcfDNA was increased >50% on day 1 post-LTx, presumably from ischemia/reperfusion damage, but rapidly declined in patients without graft injury within 7 to 10 d to a median
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.1002286