ArticleJournal of clinical and translational hepatology2026
Single-cell Sequencing Reveals Neutrophil Extracellular Traps in Association with Endotheliopathy and Immunothrombosis in Hepatitis B Virus-related Acute-on-chronic Liver Failure.
Article in Journal of clinical and translational hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background and Aims: Immunothrombosis, the interplay between immune activation and coagulation, contributes to disease progression in inflammatory disorders. Its role in hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and the involvement of neutrophil extracellular traps (NETs) remain unclear. This study aimed to elucidate NETs-mediated immunothrombosis in HBV-ACLF. Methods: Liver single-cell RNA sequencing data from HBV-ACLF patients and healthy controls were analyzed to define immune and endothelial transcriptional profiles. A cohort of 46 HBV-ACLF patients, 20 chronic hepatitis B patients, and 20 healthy controls was assessed for circulating NETs, endothelial injury markers, and coagulation parameters. Histopathology and Results: NETs were markedly elevated in HBV-ACLF and correlated with endothelial injury markers (syndecan-1, von Willebrand factor, soluble thrombomodulin), coagulopathy, and prognostic scores. Histology revealed NETs colocalization with endothelial cells and platelets within hepatic microthrombi. NETs from patient neutrophils impaired endothelial integrity and enhanced procoagulant activity Conclusions: NETs are associated with endothelial injury and immunothrombosis in HBV-ACLF. Mechanistic analyses suggest a role for TLR2 and C5aR1 pathways in NETs formation, indicating potential targets for future therapeutic investigation.
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