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

Graft-derived cell-free DNA – an early rejection marker in liver transplantation

by Anna Fischer
Doctoral thesis
Date of Examination:2020-02-18
Date of issue:2020-02-18
Advisor:Prof. Dr. Dr. Michael Oellerich
Referee:Prof. Dr. Dr. Michael Oellerich
Referee:PD Dr. Thomas Lorf
Persistent Address: http://dx.doi.org/10.53846/goediss-7852

 

 

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Abstract

English

Graft-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. 
Keywords: graft-derived cell-free DNA; liver transplantation; rejection biomarker; digital droplet PCR; GcfDNA; liquid biopsy
 
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