Single-cell Sequencing Reveals Neutrophil Extracellular Traps in Association with Endotheliopathy and Immunothrombosis in Hepatitis B Virus-related Acute-on-chronic Liver Failure

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: assays examined NETs distribution and endothelial interactions. Results: . Mechanistically, toll-like receptor 2 (TLR2) and complement component 5a receptor 1 (C5aR1) signaling were involved in NETs formation, and their pharmacological inhibition reduced NETs generation. 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.