ArticleVirchows Archiv : an international journal of pathology2022
Neutrophil extracellular traps enriched with IL-1β and IL-17A participate in the hepatic inflammatory process of patients with non-alcoholic steatohepatitis.
Article in Virchows Archiv : an international journal of pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 46 citations in OpenAlex.
- The emerging role of neutrophil extracellular traps in liver diseases: a narrative review.Medical molecular morphology · 2026Review
- Systemic metabolic dysfunction drives platelet-mediated inflammation, fibrogenesis, and hepatocarcinogenesis in metabolic dysfunction-associated steatotic liver disease.Clinical and molecular hepatology · 2026Review
- When the Liver Flares: Inflammatory and Immunometabolic Mechanisms Driving the Transition from MASLD to MASH.Inflammation · 2026Review
- Neutrophil extracellular Trap-related genes in NAFLD: Biomarkers and therapeutic targets.Clinical and experimental medicine · 2026Article
- Regulated necrosis at the crossroads of liver inflammation and cancer development.Nature reviews. Gastroenterology & hepatology · 2026Review
- PAD4+ neutrophils promote hepatic stellate cell activation and accelerate MASH fibrosis progression viaNET-DNA/TAOK1/MAPK pathways.JCI insight · 2026Article
- Hypoxia-inducible factors in the immunometabolism of metabolic dysfunction-associated steatotic liver disease (MASLD): molecular mechanisms and therapeutic implications.Frontiers in physiology · 2026Article
- The Role of Neutrophils in Non-Alcoholic Fatty Liver Disease: Mechanisms and Clinical Significance.Journal of inflammation research · 2026Review
- Prognostic significance of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in hepatocellular carcinoma: a retrospective multicenter study on overall and recurrence-free survival following liver resection or liver transplantation.Frontiers in immunology · 2026Article
- The Intriguing Roles of Cytokines in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.Current obesity reports · 2025Review
- Myeloperoxidase, extracellular DNA and neutrophil extracellular trap formation in the animal models of metabolic dysfunction-associated steatotic liver disease.World journal of gastroenterology · 2025Article
- Article
- Metabolic Implications of Elevated Neutrophil Extracellular Traps in Polycystic Ovary Syndrome: A Focus on Hepatic Glycolysis.Biomolecules · 2025Article
- Therapeutic Strategies for MASH: An Update on Drug Candidates Under Investigation in Late-Phase Clinical Trials.International journal of translational medicine (Basel, Switzerland) · 2025Article
- Neutrophils in MASLD and MASH.BMB reports · 2025Review
- Pathophysiological Role of Neutrophil Extracellular Traps in Diet-Induced Obesity and Metabolic Syndrome in Animal Models.Nutrients · 2025Review
- IL-1beta expressing neutrophil extracellular traps inFrontiers in immunology · 2025Article
- Innate immune cells link dietary cues to normal and abnormal metabolic regulation.Nature immunology · 2025Review
- Histologic evidence of neutrophil extracellular traps and fibrin(ogen) deposition in liver biopsies from patients with inflammatory liver disease.Research and practice in thrombosis and haemostasis · 2025Article
- Insights of gut-liver axis in hepatic diseases: Mechanisms, clinical implications, and therapeutic potentials.World journal of gastrointestinal pharmacology and therapeutics · 2024Review
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of various non-infectious inflammatory and thrombotic diseases. We investigated the presence and possible associations of NETs with various histopathologic parameters in patients with non-alcoholic steatohepatitis (NASH). We retrospectively assessed 20 liver biopsy specimens from patients with non-alcoholic fatty liver disease (NAFLD), including 17 specimens with NASH, and 14 control specimens. NETs were identified with confocal microscopy as extracellular structures with co-localization of neutrophil elastase (NE) and citrullinated histone-3. Interleukin-1β (IL-1β) and IL-17A were assessed with the same methodology. Histologic features of NAFLD were semi-quantitatively evaluated, and correlated with presence of NETs, neutrophil density, and platelet density/aggregates (assessed by immunohistochemistry for NE and CD42b, respectively). NETs were identified in 94.1% (16/17) of the NASH biopsy specimens; they were absent from all other NAFLD and control specimens. The presence of NETs was strongly correlated with steatosis (p = 0.003), ballooning degeneration (p < 0.001), lobular inflammation (p < 0.001), portal inflammation (p < 0.001), NAS score (p = 0.001), stage (p = 0.001), and diagnosis of NASH (p < 0.001). NETs were decorated with IL-1β and IL-17A. Platelet aggregates were much larger in NASH specimens, as compared to controls. In conclusion, NETs are implicated in the pathogenesis of NASH. Their associations with inflammation, ballooning degeneration (a hallmark of NASH), and stage emphasize their role in the disease process. In this setting, NETs provide a vehicle for IL-1β and IL-17A. In addition, platelet aggregation in hepatic sinusoids implies a role for thromboinflammation in NASH, and may explain the low peripheral blood platelet counts reported in patients with NASH.
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