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Open AccessFeature PaperArticle

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

1
Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité—Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 13353 Berlin, Germany
2
Berlin Institute of Health (BIH), 10178 Berlin, Germany
3
Department of General, Visceral and Transplantation Surgery, Universitätsklinikum Münster, 48149 Münster, Germany
4
Institute of Pathology, Charité—Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, 10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(5), 1543; https://doi.org/10.3390/jcm9051543
Received: 27 April 2020 / Revised: 15 May 2020 / Accepted: 17 May 2020 / Published: 20 May 2020
(This article belongs to the Special Issue Liver Transplantation: Improving Results under Worsening Conditions)
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. View Full-Text
Keywords: damage-associated molecular patterns; C-reactive proteins; systemic immune response; sepsis; portal hepatitis; liver transplantation; cfDNA; cell-free DNA damage-associated molecular patterns; C-reactive proteins; systemic immune response; sepsis; portal hepatitis; liver transplantation; cfDNA; cell-free DNA
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Krenzien, F.; Katou, S.; Papa, A.; Sinn, B.; Benzing, C.; Feldbrügge, L.; Kamali, C.; Brunnbauer, P.; Splith, K.; Lorenz, R.R.; Ritschl, P.; Wiering, L.; Öllinger, R.; Schöning, W.; Pratschke, J.; Schmelzle, M. Increased Cell-Free DNA Plasma Concentration Following Liver Transplantation Is Linked to Portal Hepatitis and Inferior Survival. J. Clin. Med. 2020, 9, 1543.

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