Evidence map›Paper›PMID 34504150›Full record

ArticleScientific reports2021

Neutrophil extracellular traps in patients with liver cirrhosis and hepatocellular carcinoma.

Robin Zenlander, Sebastian Havervall, Maria Magnusson, Jennie Engstrand, Anna Ågren, Charlotte Thålin, Per Stål

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
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  8. Article
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  10. Interaction of inflammation and portal hypertension in cirrhosis progression.Nature reviews. Gastroenterology & hepatology · 2025
    Review
  11. Article
  12. Neutrophil Extracellular Traps Are Not Linked to Decompensation, ACLF, or Death in Clinically Stable Patients With ACLD.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Article
  13. Myeloid cells in chronic liver inflammation.Cellular & molecular immunology · 2025
    Review
  14. Article
  15. Article
  16. IL-1b-Bearing NETs: Bridging Inflammation to Early Cirrhosis in Hepatitis B.International journal of molecular sciences · 2025
    Article
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  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Robin ZenlanderDepartment of Clinical Chemistry, Karolinska University Hospital, Stockholm, Sweden. robin.zenlander@ki.se.
Sebastian HavervallDivision of Gastroenterology, Department of Specialized Medicine, Danderyd Hospital, Stockholm, Sweden.
Maria MagnussonDivision of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Jennie EngstrandDivision of Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Anna ÅgrenDepartment of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
Charlotte ThålinDepartment of Clinical Sciences, Karolinska Institutet Danderyd Hospital, Stockholm, Sweden.
Per StålDepartment of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden.
Karolinska Institutet · SEDanderyds sjukhus · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

AgedAntithrombin IIIBiomarkersCarcinoma, HepatocellularCase-Control StudiesCitrullinationDNAExtracellular TrapsFemaleHistonesHumansInflammationLiverLiver CirrhosisLiver NeoplasmsMaleAntithrombin IIIantithrombin III-protease complexBiomarkersDNAHistonesPeptide HydrolasesPeroxidase

Identifiers

PMID34504150
PMCPMC8429678
OpenAlexW3198714598

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.