Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

Abstract Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3C...

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Autores principales:	Robin Zenlander, Sebastian Havervall, Maria Magnusson, Jennie Engstrand, Anna Ågren, Charlotte Thålin, Per Stål
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/99b442543f7d466a942f11703b914336
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spelling	oai:doaj.org-article:99b442543f7d466a942f11703b9143362021-12-02T14:58:48ZNeutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma10.1038/s41598-021-97233-32045-2322https://doaj.org/article/99b442543f7d466a942f11703b9143362021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97233-3https://doaj.org/toc/2045-2322Abstract Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin–antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child–Pugh and MELD score. TAT was increased in all Child–Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.Robin ZenlanderSebastian HavervallMaria MagnussonJennie EngstrandAnna ÅgrenCharlotte ThålinPer StålNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robin Zenlander Sebastian Havervall Maria Magnusson Jennie Engstrand Anna Ågren Charlotte Thålin Per Stål Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
description	Abstract Neutrophil extracellular traps (NETs) are web-like structures consisting of DNA, histones and granule proteins, released from neutrophils in thrombus formation, inflammation, and cancer. We asked if plasma levels of the NET markers myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit)-DNA, are elevated in liver cirrhosis and hepatocellular carcinoma (HCC) and if the levels correlate with clinical parameters. MPO-DNA, H3Cit-DNA, and thrombin–antithrombin (TAT) complex, as a marker of coagulation activity, were measured using ELISA in plasma from 82 patients with HCC, 95 patients with cirrhosis and 50 healthy controls. Correlations were made to clinical parameters and laboratory data and patients were followed for a median of 22.5 months regarding thrombosis development. H3Cit-DNA was significantly (p < 0.01) elevated in plasma from cirrhosis (66.4 ng/mL) and HCC (63.8 ng/mL) patients compared to healthy controls (31.8 ng/mL). TAT levels showed similar pattern (3.1, 3.7, and 0.0 µg/mL respectively, p < 0.01). MPO-DNA was significantly (p < 0.01) elevated in cirrhosis patients (0.53 O.D.) as compared to controls (0.33 O.D.). Levels of MPO-DNA and H3Cit-DNA correlated positively with Child–Pugh and MELD score. TAT was increased in all Child–Pugh and MELD groups. In multivariable logistic regression, Child B and C liver cirrhosis were independent predictors of elevated H3Cit-DNA in plasma. Levels of MPO-DNA and H3Cit-DNA were similar in patients with or without history of thrombosis, or thrombus formation during follow-up. In conclusion, plasma markers of NET formation are elevated in liver cirrhosis and correlate to the degree of liver dysfunction in patients with liver cirrhosis and/or HCC. The presence of HCC did not further increase the plasma levels of NET markers as compared to patients with cirrhosis only.
format	article
author	Robin Zenlander Sebastian Havervall Maria Magnusson Jennie Engstrand Anna Ågren Charlotte Thålin Per Stål
author_facet	Robin Zenlander Sebastian Havervall Maria Magnusson Jennie Engstrand Anna Ågren Charlotte Thålin Per Stål
author_sort	Robin Zenlander
title	Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
title_short	Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
title_full	Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
title_fullStr	Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
title_full_unstemmed	Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
title_sort	neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/99b442543f7d466a942f11703b914336
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Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma

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