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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Veröffentlicht in:Journal of clinical medicine 2020-05, Vol.9 (5), p.1543
Hauptverfasser: 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
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container_issue 5
container_start_page 1543
container_title Journal of clinical medicine
container_volume 9
creator 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
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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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. 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source MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access
subjects Biopsy
Clinical medicine
Hemodialysis
Hepatitis
Inflammation
Laboratories
Liver
Liver transplants
Neutrophils
Plasma
Sepsis
Steroids
Thermal cycling
Transplants & implants
title Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival
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