{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:09:22Z","timestamp":1791929362984,"version":"4.3.4"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T00:00:00Z","timestamp":1639267200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Acute liver failure (ALF) is characterized by significant changes in the hemostatic system and by systemic inflammation. The formation of neutrophil extracellular traps (NETs), in which an activated neutrophil expels its DNA, histones, and granular enzymes, such as myeloperoxidase (MPO), has been associated with immune\u2010mediated and thrombotic diseases. We hypothesized that formation of NETs in patients with ALF contributes to progression of disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A total of 676 patients with ALF (international normalized ratio [INR], \u22651.5) or severe acute liver injury (ALI; INR, \u22652.0) were recruited from the U.S. ALF Study Group Registry between 2011 and 2018, of whom 308 patients (45.6%) had acetaminophen\u2010induced ALF. Up to 21 days after admission, 483 patients (71.5%) survived without liver transplantation (LT). Levels of cell\u2010free DNA (cfDNA) and the specific NET marker MPO\u2010DNA complexes were measured in plasma samples obtained on admission and compared to levels in healthy controls. In addition, liver tissue obtained at transplantation of 20 ALF patients was stained for NETs. Levels of cfDNA were 7.1\u2010fold, and MPO\u2010DNA complexes 2.5\u2010fold, higher in patients with ALF compared to healthy controls. cfDNA levels were not associated with 21\u2010day transplant\u2010free survival, but were higher in those patients with more\u2010severe disease on admission, as reflected by various laboratory and clinical parameters. MPO\u2010DNA levels were 30% higher in patients with ALF who died or required urgent LT. Liver tissue of ALF patients stained positive for NETs in 12 of 18 evaluable patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Here, we provide evidence for NET formation in patients with ALF. Elevated plasma levels of MPO\u2010DNA complexes in patients with ALF were associated with poor outcome, which suggests that NET formation contributes to disease progression.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32174","type":"journal-article","created":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T12:23:02Z","timestamp":1632572582000},"page":"623-633","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":70,"title":["Generation of neutrophil extracellular traps in patients with acute liver failure is associated with poor outcome"],"prefix":"10.1097","volume":"75","author":[{"given":"Fien A.","family":"von Meijenfeldt","sequence":"first","affiliation":[{"name":"Surgical Research Laboratory,Department of Surgery,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9901-854X","authenticated-orcid":false,"given":"R. Todd","family":"Stravitz","sequence":"additional","affiliation":[{"name":"Hume\u2010Lee Transplant Center of Virginia Commonwealth University,Richmond,Virginia,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences,Medical University of South Carolina,Charleston,South Carolina,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelle","family":"Adelmeijer","sequence":"additional","affiliation":[{"name":"Surgical Research Laboratory,Department of Surgery,University of Groningen,University Medical Center Groningen,Groningen,The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoh","family":"Zen","sequence":"additional","affiliation":[{"name":"Department of Pathology,Institute of Liver Studies,King\u2019s College 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