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Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival

Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits...

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Autores principales: Krenzien, Felix, Katou, Shadi, Papa, Alba, Sinn, Bruno, Benzing, Christian, Feldbrügge, Linda, Kamali, Can, Brunnbauer, Philipp, Splith, Katrin, Lorenz, Ralf Roland, Ritschl, Paul, Wiering, Leke, Öllinger, Robert, Schöning, Wenzel, Pratschke, Johann, Schmelzle, Moritz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291032/
https://www.ncbi.nlm.nih.gov/pubmed/32443763
http://dx.doi.org/10.3390/jcm9051543
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author Krenzien, Felix
Katou, Shadi
Papa, Alba
Sinn, Bruno
Benzing, Christian
Feldbrügge, Linda
Kamali, Can
Brunnbauer, Philipp
Splith, Katrin
Lorenz, Ralf Roland
Ritschl, Paul
Wiering, Leke
Öllinger, Robert
Schöning, Wenzel
Pratschke, Johann
Schmelzle, Moritz
author_facet Krenzien, Felix
Katou, Shadi
Papa, Alba
Sinn, Bruno
Benzing, Christian
Feldbrügge, Linda
Kamali, Can
Brunnbauer, Philipp
Splith, Katrin
Lorenz, Ralf Roland
Ritschl, Paul
Wiering, Leke
Öllinger, Robert
Schöning, Wenzel
Pratschke, Johann
Schmelzle, Moritz
author_sort Krenzien, Felix
collection PubMed
description Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits highly proinflammatory effects via DNA sensors. Herein, we measured cfDNA after liver transplantation and found elevated levels when organs from resuscitated donors were transplanted. High levels of cfDNA were associated with high C-reactive protein, leukocytosis as well as granulocytosis in the recipient. In addition to increased systemic immune responses, portal hepatitis was observed, which was associated with increased interface activity and a higher numbers of infiltrating neutrophils and eosinophils in the graft. In fact, the cfDNA was an independent significant factor in multivariate analysis and increased concentration of cfDNA was associated with inferior 1-year survival. Moreover, cfDNA levels were found to be decreased significantly during the postoperative course when patients underwent continuous veno-venous haemofiltration. In conclusion, patients receiving livers from resuscitated donors were characterised by high postoperative cfDNA levels. Those patients showed pronounced portal hepatitis and systemic inflammatory responses in the short term leading to a high mortality. Further studies are needed to evaluate the clinical relevance of cfDNA clearance by haemoadsorption and haemofiltration in vitro and in vivo.
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spelling pubmed-72910322020-06-17 Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival Krenzien, Felix Katou, Shadi Papa, Alba Sinn, Bruno Benzing, Christian Feldbrügge, Linda Kamali, Can Brunnbauer, Philipp Splith, Katrin Lorenz, Ralf Roland Ritschl, Paul Wiering, Leke Öllinger, Robert Schöning, Wenzel Pratschke, Johann Schmelzle, Moritz J Clin Med Article Donor organ quality is crucial for transplant survival and long-term survival of patients after liver transplantation. Besides bacterial and viral infections, endogenous damage-associated molecular patterns (DAMPs) can stimulate immune responses. Cell-free DNA (cfDNA) is one such DAMP that exhibits highly proinflammatory effects via DNA sensors. Herein, we measured cfDNA after liver transplantation and found elevated levels when organs from resuscitated donors were transplanted. High levels of cfDNA were associated with high C-reactive protein, leukocytosis as well as granulocytosis in the recipient. In addition to increased systemic immune responses, portal hepatitis was observed, which was associated with increased interface activity and a higher numbers of infiltrating neutrophils and eosinophils in the graft. In fact, the cfDNA was an independent significant factor in multivariate analysis and increased concentration of cfDNA was associated with inferior 1-year survival. Moreover, cfDNA levels were found to be decreased significantly during the postoperative course when patients underwent continuous veno-venous haemofiltration. In conclusion, patients receiving livers from resuscitated donors were characterised by high postoperative cfDNA levels. Those patients showed pronounced portal hepatitis and systemic inflammatory responses in the short term leading to a high mortality. Further studies are needed to evaluate the clinical relevance of cfDNA clearance by haemoadsorption and haemofiltration in vitro and in vivo. MDPI 2020-05-20 /pmc/articles/PMC7291032/ /pubmed/32443763 http://dx.doi.org/10.3390/jcm9051543 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Krenzien, Felix
Katou, Shadi
Papa, Alba
Sinn, Bruno
Benzing, Christian
Feldbrügge, Linda
Kamali, Can
Brunnbauer, Philipp
Splith, Katrin
Lorenz, Ralf Roland
Ritschl, Paul
Wiering, Leke
Öllinger, Robert
Schöning, Wenzel
Pratschke, Johann
Schmelzle, Moritz
Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title_full Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title_fullStr Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title_full_unstemmed Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title_short Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
title_sort increased cell-free dna plasma concentration following liver transplantation is linked to portal hepatitis and inferior survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291032/
https://www.ncbi.nlm.nih.gov/pubmed/32443763
http://dx.doi.org/10.3390/jcm9051543
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