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Zirkulierende zellfreie Transplantat-DNA zur Früherkennung einer Abstoßung in der Lebertransplantation

dc.contributor.advisorOellerich, Michael Prof. Dr. Dr.
dc.contributor.authorFischer, Anna
dc.date.accessioned2020-02-18T13:03:19Z
dc.date.available2020-02-25T23:50:02Z
dc.date.issued2020-02-18
dc.identifier.urihttp://hdl.handle.net/21.11130/00-1735-0000-0005-1325-C
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-7852
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc610de
dc.titleZirkulierende zellfreie Transplantat-DNA zur Früherkennung einer Abstoßung in der Lebertransplantationde
dc.typedoctoralThesisde
dc.title.translatedGraft-derived cell-free DNA – an early rejection marker in liver transplantationde
dc.contributor.refereeOellerich, Michael Prof. Dr. Dr.
dc.date.examination2020-02-18
dc.description.abstractengGraft-derived cell-free DNA (GcfDNA) is a promising non-invasive organ integrity biomarker. In a prospective, observational, multicenter trial plasma GcfDNA was investigated in 115 adults post liver transplantation (LTx) at three German transplant centers. GcfDNA was highly elevated (>50%) on day one post-LTx, presumably due to ischemia/reperfusion damage, but rapidly decreased in patients without graft injury within 7 to 10 days to a median <10% baseline where it remained for the one year observation period. GcfDNA values were highly elevated (median 29.6%, 95% CI 23.6%–41.0%) in 31 samples during 17 biopsy-proven acute rejection episodes compared to 282 samples from 88 patients during stable periods (median 3.3%, 95% CI 2.9%–3.7%; p < 0.001), whereas only slightly higher values were found in 68 samples from 17 Hepatitis C (HCV+) patients (median 5.9%, 95% CI 4.4%–10.3%). Traditional liver function tests (LFTs) had low overall correlations (r = 0.28–0.62) with GcfDNA and greater overlap between acute rejection, HCV+ patients, and stable periods. Diagnostic sensitivity and specificity were 90.3% (95% CI 74.2%–98.0%) and 92.9% (95% CI 89.3%–95.6%) respectively, for GcfDNA at a threshold value of 10%. The area under the receiver operator characteristic curve for GcfDNA ((97.1%, 95% CI 93.4%–100%) was highest compared to same day conventional LFTs. Conclusion: In this study, determination of GcfDNA in plasma by ddPCR allowed for earlier and more sensitive discrimination of acute rejection in LTx patients as compared with conventional LFTs. de
dc.contributor.coRefereeLorf, Thomas PD Dr.
dc.subject.enggraft-derived cell-free DNAde
dc.subject.engliver transplantationde
dc.subject.engrejection biomarkerde
dc.subject.engdigital droplet PCRde
dc.subject.engGcfDNAde
dc.subject.engliquid biopsyde
dc.identifier.urnurn:nbn:de:gbv:7-21.11130/00-1735-0000-0005-1325-C-6
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullChirurgie - Allgemein- und Gesamtdarstellungen (PPN619875968)de
dc.subject.gokfullDiagnostik {Medizin} (PPN619875739)de
dc.description.embargoed2020-02-25
dc.identifier.ppn169032418X


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