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In this branch of the immune system, neutrophils are considered key cellular mediators. To better understand the implication of neutrophils in the distinct stages of the disease, HBV-infected patients were enrolled in this study and categorized into three groups: patients with acute infection, chronic infection under treatment, and at early cirrhotic stage. To elucidate the role of inflammatory mediators and cellular mechanisms of neutrophilic origin in the course of the infection, both ex vivo and in vitro studies were performed. Increased levels of C-C motif chemokine ligand 2 (CCL2), interleukin (IL)-18, IL-33, and citrullinated histone H3 (CitH3)\u2014an accurate marker of neutrophil extracellular traps (NETs)\u2014were detected in the circulation of patients with acute infection or early cirrhosis. In parallel, sera from the aforementioned patient groups induced the formation of IL-1b-bearing NETs in neutrophils from healthy individuals. These inflammatory NETs affected primary fibroblasts towards acquiring a pro-fibrotic phenotype. These results suggest that NETs could be regarded as mediators in hepatitis B manifestations, while their therapeutic targeting could enhance the management of early-stage cirrhotic patients.<\/jats:p>","DOI":"10.3390\/ijms26125733","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T10:47:22Z","timestamp":1750070842000},"page":"5733","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["IL-1b-Bearing NETs: Bridging Inflammation to Early Cirrhosis in Hepatitis B"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7558-5133","authenticated-orcid":false,"given":"Maria","family":"Ntinopoulou","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Biological Applications & Technology, Faculty of Health Sciences, University of Ioannina, 45332 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4296-3414","authenticated-orcid":false,"given":"Theocharis","family":"Konstantinidis","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Chalkidou","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, University General Hospital of Alexandroupolis, 68100 Alexadroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Papagianni","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Biological Applications & Technology, Faculty of Health Sciences, University of Ioannina, 45332 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9436-5848","authenticated-orcid":false,"given":"Aikaterini","family":"Skeva","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Panopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Department of Medicine, Faculty of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akrivi","family":"Chrysanthopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunology, Department of Biological Applications & Technology, Faculty of Health Sciences, University of Ioannina, 45332 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.arcmed.2006.10.001","article-title":"Liver Fibrosis and Chronic Viral Hepatitis","volume":"38","author":"Kershenobich","year":"2007","journal-title":"Arch. Med. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/liv.12710","article-title":"Reversibility of Hepatitis B Virus Cirrhosis after Therapy: Who and Why?","volume":"35","author":"Bedossa","year":"2015","journal-title":"Liver Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.cld.2016.06.003","article-title":"Liver Fibrosis Reversion after Suppression of Hepatitis B Virus","volume":"20","author":"Rockey","year":"2016","journal-title":"Clin. Liver disease"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"6457","DOI":"10.3748\/wjg.v20.i21.6457","article-title":"Virus-Related Liver Cirrhosis: Molecular Basis and Therapeutic Options","volume":"20","author":"Lin","year":"2014","journal-title":"World J. Gastroenterol. WJG"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ringehan, M., McKeating, J.A., and Protzer, U. (2017). Viral Hepatitis and Liver Cancer. Philos. Trans. R. Soc. B Biol. Sci., 372.","DOI":"10.1098\/rstb.2016.0274"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00046-19","DOI":"10.1128\/CMR.00046-19","article-title":"Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy","volume":"33","author":"Nguyen","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.3748\/wjg.v27.i25.3762","article-title":"Management of Hepatitis B Virus Infection in Patients with Inflammatory Bowel Disease under Immunosuppressive Treatment","volume":"27","author":"Axiaris","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhao, J., Bian, D., Liao, H., Wang, Y., Ren, Y., Jiang, Y., Liu, S., Chen, X., Hu, Z., and Duan, Z. (2023). Serum HBsAg and HBcrAg Is Associated with Inflammation in HBeAg-Positive Chronic Hepatitis B Patients. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1083912"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A Global Scientific Strategy to Cure Hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.4254\/wjh.v7.i21.2319","article-title":"Innate Immune Recognition of Hepatitis B Virus","volume":"7","author":"Liu","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Yang, G., Wan, P., Zhang, Y., Tan, Q., Qudus, M.S., Yue, Z., Luo, W., Zhang, W., Ouyang, J., and Li, Y. (2022). Innate Immunity, Inflammation, and Intervention in HBV Infection. Viruses, 14.","DOI":"10.3390\/v14102275"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhong, S., Zhang, T., Tang, L., and Li, Y. (2021). Cytokines and Chemokines in HBV Infection. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.805625"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5202898","DOI":"10.1155\/2022\/5202898","article-title":"Circulating IL-1\u03b2, IL-17, and IP-10 as Potential Predictors of Hepatitis B Virus Infection Prognosis","volume":"2022","author":"Su","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s13027-024-00580-9","article-title":"Expression of 10 Circulating Cytokines\/Chemokines in HBV-Related Liver Disease","volume":"19","author":"Jia","year":"2024","journal-title":"Infect. Agents Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110284","DOI":"10.1016\/j.celrep.2021.110284","article-title":"Macrophages Activated by Hepatitis B Virus Have Distinct Metabolic Profiles and Suppress the Virus via IL-1\u03b2 to Downregulate PPAR\u03b1 and FOXO3","volume":"38","author":"Li","year":"2022","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Dimitriadis, K., Katelani, S., Pappa, M., Fragkoulis, G.E., and Androutsakos, T. (2023). The Role of Interleukins in HBV Infection: A Narrative Review. J. Pers. Med., 13.","DOI":"10.3390\/jpm13121675"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/1348-0421.12947","article-title":"Cytokines Profile in Patients with Acute and Chronic Hepatitis B Infection","volume":"66","author":"Ribeiro","year":"2022","journal-title":"Microbiol. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.immuni.2021.06.006","article-title":"The Neutrophil","volume":"54","author":"Burn","year":"2021","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1182\/blood-2008-01-132860","article-title":"Toll-like Receptor\u2013Mediated Activation of Neutrophils by Influenza A Virus","volume":"112","author":"Wang","year":"2008","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.coph.2011.06.007","article-title":"The Role of TLRs in Neutrophil Activation","volume":"11","author":"Prince","year":"2011","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41385-021-00397-4","article-title":"Neutrophils in Respiratory Viral Infections","volume":"14","author":"Johansson","year":"2021","journal-title":"Mucosal Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.jhep.2013.12.005","article-title":"A TLR2\/S100A9\/CXCL-2 Signaling Network Is Necessary for Neutrophil Recruitment in Acute and Chronic Liver Injury in the Mouse","volume":"60","author":"Moles","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rosales, C. (2018). Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?. Front. Physiol., 9.","DOI":"10.3389\/fphys.2018.00113"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.it.2019.04.012","article-title":"Neutrophil Diversity in Health and Disease","volume":"40","author":"Fridlender","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Venetsanopoulou, A.I., Ntinopoulou, M., Papagianni, E., Koletsos, N., Voulgari, P.V., and Chrysanthopoulou, A. (2024). Neutrophil Extracellular Traps as Immunofibrotic Mediators in RA-ILD; Pilot Evaluation of the Nintedanib Therapy. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1480594"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.1172\/JCI141374","article-title":"Complement and Tissue Factor-Enriched Neutrophil Extracellular Traps Are Key Drivers in COVID-19 Immunothrombosis","volume":"130","author":"Skendros","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Gierlikowska, B., Stachura, A., Gierlikowski, W., and Demkow, U. (2021). Phagocytosis, Degranulation and Extracellular Traps Release by Neutrophils-The Current Knowledge, Pharmacological Modulation and Future Prospects. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.666732"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/JLB.4MIR0220-574RR","article-title":"Neutrophils at the Crossroads of Innate and Adaptive Immunity","volume":"108","author":"Rosales","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1136\/annrheumdis-2018-213181","article-title":"REDD1\/Autophagy Pathway Promotes Thromboinflammation and Fibrosis in Human Systemic Lupus Erythematosus (SLE) through NETs Decorated with Tissue Factor (TF) and Interleukin-17A (IL-17A)","volume":"78","author":"Frangou","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ntinopoulou, M., Cassimos, D., Roupakia, E., Kolettas, E., Panopoulou, M., Mantadakis, E., Konstantinidis, T., and Chrysanthopoulou, A. (2023). \u0399nterleukin-17A-Enriched Neutrophil Extracellular Traps Promote Immunofibrotic Aspects of Childhood Asthma Exacerbation. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082104"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/path.4359","article-title":"Neutrophil Extracellular Traps Promote Differentiation and Function of Fibroblasts","volume":"233","author":"Chrysanthopoulou","year":"2014","journal-title":"J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1182\/blood.V66.6.1251.1251","article-title":"Hepatitis B Virus DNA Is Enriched in Polymorphonuclear Leukocytes","volume":"66","author":"Hoar","year":"1985","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.imbio.2014.07.008","article-title":"The Hepatitis B Virus e Antigen Suppresses the Respiratory Burst and Mobility of Human Monocytes and Neutrophils","volume":"219","author":"Leu","year":"2014","journal-title":"Immunobiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1007\/s12072-024-10689-z","article-title":"HBeAg Induces Neutrophils Activation Impairing NK Cells Function in Patients with Chronic Hepatitis B","volume":"18","author":"Feng","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Gschwandtner, M., Derler, R., and Midwood, K.S. (2019). More Than Just Attractive: How CCL2 Influences Myeloid Cell Behavior Beyond Chemotaxis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02759"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1128\/IAI.00067-11","article-title":"Monocyte Chemoattractant Protein 1 Regulates Pulmonary Host Defense via Neutrophil Recruitment during Escherichia Coli Infection","volume":"79","author":"Balamayooran","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.4049\/jimmunol.167.5.2879","article-title":"A Role for IL-18 in Neutrophil Activation","volume":"167","author":"Leung","year":"2001","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.jhep.2019.12.017","article-title":"IL-33\/ST2 Pathway Regulates Neutrophil Migration and Predicts Outcome in Patients with Severe Alcoholic Hepatitis","volume":"72","author":"Artru","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1038\/cmi.2017.163","article-title":"Characterization and Allergic Role of IL-33-Induced Neutrophil Polarization","volume":"15","author":"Sun","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hofbauer, T.M., Ondracek, A.S., Mangold, A., Scherz, T., Nechvile, J., Seidl, V., Brostjan, C., and Lang, I.M. (2020). Neutrophil Extracellular Traps Induce MCP-1 at the Culprit Site in ST-Segment Elevation Myocardial Infarction. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.564169"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4049\/jimmunol.1202388","article-title":"Neutrophil Extracellular Trap-Associated Protein Activation of the NLRP3 Inflammasome Is Enhanced in Lupus Macrophages","volume":"190","author":"Kahlenberg","year":"2013","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jhep.2017.09.010","article-title":"IL-33 Exacerbates Liver Sterile Inflammation by Amplifying Neutrophil Extracellular Trap Formation","volume":"68","author":"Yazdani","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1136\/annrheumdis-2014-205958","article-title":"Neutrophil Extracellular Traps Regulate IL-1\u03b2-Mediated Inflammation in Familial Mediterranean Fever","volume":"75","author":"Apostolidou","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"ii92","DOI":"10.1136\/ard.2004.028332","article-title":"Defining a Role for Fibroblasts in the Persistence of Chronic Inflammatory Joint Disease","volume":"63","author":"Buckley","year":"2004","journal-title":"Ann. Rheum. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e149538","DOI":"10.1172\/JCI149538","article-title":"Fibroblast Pathology in Inflammatory Diseases","volume":"131","author":"Wei","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S1471-4906(01)01863-4","article-title":"Fibroblasts Regulate the Switch from Acute Resolving to Chronic Persistent Inflammation","volume":"22","author":"Buckley","year":"2001","journal-title":"Trends Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.yjmcc.2015.11.016","article-title":"Role of Inflammatory Cells in Fibroblast Activation","volume":"93","author":"Hartupee","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1093\/cvr\/cvu062","article-title":"Crosstalk between Fibroblasts and Inflammatory Cells","volume":"102","author":"Miteva","year":"2014","journal-title":"Cardiovasc. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6499","DOI":"10.1038\/s41467-022-34241-5","article-title":"Understanding Fibrosis Pathogenesis via Modeling Macrophage-Fibroblast Interplay in Immune-Metabolic Context","volume":"13","author":"Setten","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and Chemokines: At the Crossroads of Cell Signalling and Inflammatory Disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Sokol, C.L., and Luster, A.D. (2015). The Chemokine System in Innate Immunity. Cold Spring Harb. Perspect. Biol., 7.","DOI":"10.1101\/cshperspect.a016303"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: Function, Regulation, and Involvement in Disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1172\/JCI5208","article-title":"Chronic Inflammation Upregulates Chemokine Receptors and Induces Neutrophil Migration to Monocyte Chemoattractant Protein-1","volume":"103","author":"Johnston","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbadis.2012.11.004","article-title":"Chemokines in Tissue Fibrosis","volume":"1832","author":"Sahin","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ihim, S.A., Abubakar, S.D., Zian, Z., Sasaki, T., Saffarioun, M., Maleknia, S., and Azizi, G. (2022). Interleukin-18 Cytokine in Immunity, Inflammation, and Autoimmunity: Biological Role in Induction, Regulation, and Treatment. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.919973"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/eji.200535402","article-title":"Expression and Alternative Processing of IL-18 in Human Neutrophils","volume":"36","author":"Robertson","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_57","first-page":"436","article-title":"Interleukin-18 Primes the Oxidative Burst of Neutrophils in Response to Formyl-Peptides: Role of Cytochrome B558 Translocation and N-Formyl Peptide Receptor Endocytosis","volume":"12","author":"Elbim","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Yasuda, K., Nakanishi, K., and Tsutsui, H. (2019). Interleukin-18 in Health and Disease. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030649"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Baggio, C., Bindoli, S., Guidea, I., Doria, A., Oliviero, F., and Sfriso, P. (2023). IL-18 in Autoinflammatory Diseases: Focus on Adult Onset Still Disease and Macrophages Activation Syndrome. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241311125"},{"key":"ref_60","first-page":"156890","article-title":"IL-18 Serum Level in Adult Onset Still\u2019s Disease: A Marker of Disease Activity","volume":"2012","author":"Colafrancesco","year":"2012","journal-title":"Int. J. Inflamm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1002\/hep.32776","article-title":"Interleukin-18 Signaling Promotes Activation of Hepatic Stellate Cells in Mouse Liver Fibrosis","volume":"77","author":"Knorr","year":"2023","journal-title":"Hepatology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nri.2016.95","article-title":"Interleukin-33 in Health and Disease","volume":"16","author":"Liew","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.immuni.2013.07.018","article-title":"Interleukin-33-Dependent Innate Lymphoid Cells Mediate Hepatic Fibrosis","volume":"39","author":"McHedlidze","year":"2013","journal-title":"Immunity"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/cmi.2016.63","article-title":"Interleukin-33 Drives Hepatic Fibrosis through Activation of Hepatic Stellate Cells","volume":"15","author":"Tan","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-024-01933-x","article-title":"Neutrophil Extracellular Traps in Homeostasis and Disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"805","DOI":"10.4049\/jimmunol.1800871","article-title":"Hepatitis B Virus Inhibits Neutrophil Extracellular Trap Release by Modulating Reactive Oxygen Species Production and Autophagy","volume":"202","author":"Hu","year":"2019","journal-title":"J. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/cac2.12388","article-title":"Elevated Neutrophil Extracellular Traps by HBV-mediated S100A9-TLR4\/RAGE-ROS Cascade Facilitate the Growth and Metastasis of Hepatocellular Carcinoma","volume":"43","author":"Zhan","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrdp.2018.35","article-title":"Hepatitis B Virus Infection","volume":"4","author":"Yuen","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1002\/hep.26102","article-title":"Circulating Neutrophil Dysfunction in Acute Liver Failure","volume":"57","author":"Taylor","year":"2013","journal-title":"Hepatology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"eaar7754","DOI":"10.1126\/sciimmunol.aar7754","article-title":"Type 3 Cytokines IL-17A and IL-22 Drive TGF-\u03b2-Dependent Liver Fibrosis","volume":"3","author":"Fabre","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zenlander, R., Havervall, S., Magnusson, M., Engstrand, J., \u00c5gren, A., Th\u00e5lin, C., and St\u00e5l, P. (2021). Neutrophil Extracellular Traps in Patients with Liver Cirrhosis and Hepatocellular Carcinoma. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-97233-3"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sehgal, R., Kaur, N., Maiwall, R., Ramakrishna, G., Maras, J.S., and Trehanpati, N. (2022). Plasma Proteomic Analysis Identified Proteins Associated with Faulty Neutrophils Functionality in Decompensated Cirrhosis Patients with Sepsis. Cells, 11.","DOI":"10.3390\/cells11111745"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wu, W., Sun, S., Wang, Y., Zhao, R., Ren, H., Li, Z., Zhao, H., Zhang, Y., Sheng, J., and Chen, Z. (2021). Circulating Neutrophil Dysfunction in HBV-Related Acute-on-Chronic Liver Failure. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.620365"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/0016-5085(92)91122-K","article-title":"Serum Levels of Cytokines in Chronic Liver Diseases","volume":"103","author":"Tilg","year":"1992","journal-title":"Gastroenterology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1080\/00365520802179925","article-title":"Impaired Counter-Regulation of Interleukin-1 by the Soluble IL-1 Receptor Type II in Patients with Chronic Liver Disease","volume":"43","author":"Ludwiczek","year":"2008","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"G1324","DOI":"10.1152\/ajpgi.90564.2008","article-title":"Interleukin-1 Participates in the Progression from Liver Injury to Fibrosis","volume":"296","author":"Gieling","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/j.jaci.2017.02.021","article-title":"Regulated in Development and DNA Damage Responses 1 (REDD1) Links Stress with IL-1\u03b2-Mediated Familial Mediterranean Fever Attack through Autophagy-Driven Neutrophil Extracellular Traps","volume":"140","author":"Skendros","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Mitroulis, I., Kambas, K., Chrysanthopoulou, A., Skendros, P., Apostolidou, E., Kourtzelis, I., Drosos, G.I., Boumpas, D.T., and Ritis, K. (2011). Neutrophil Extracellular Trap Formation Is Associated with IL-1\u03b2 and Autophagy-Related Signaling in Gout. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0029318"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41573-019-0037-0","article-title":"Therapeutic Strategies for Hepatitis B Virus Infection: Towards a Cure","volume":"18","author":"Fanning","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3748\/wjg.v13.i1.125","article-title":"Antiviral Therapy and Resistance with Hepatitis B Virus Infection","volume":"13","author":"Tillmann","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.antiviral.2013.01.006","article-title":"Chronic Hepatitis B: What Should Be the Goal for New Therapies?","volume":"98","author":"Block","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.4049\/jimmunol.1701643","article-title":"REDD1\/Autophagy Pathway Is Associated with Neutrophil-Driven IL-1\u03b2 Inflammatory Response in Active Ulcerative Colitis","volume":"200","author":"Angelidou","year":"2018","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Saffarzadeh, M., Juenemann, C., Queisser, M.A., Lochnit, G., Barreto, G., Galuska, S.P., Lohmeyer, J., and Preissner, K.T. (2012). Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0032366"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An Open-Source Platform for Biological-Image Analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mitroulis, I., Chrysanthopoulou, A., Divolis, G., Ioannidis, C., Ntinopoulou, M., Tasis, A., Konstantinidis, T., Antoniadou, C., Soteriou, N., and Lallas, G. (2022). A Gene Expression Map of Host Immune Response in Human Brucellosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.951232"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1002\/art.30586","article-title":"Tissue Factor-Thrombin Signaling Enhances the Fibrotic Activity of Myofibroblasts in Systemic Sclerosis through up-Regulation of Endothelin Receptor A","volume":"63","author":"Chrysanthopoulou","year":"2011","journal-title":"Arthritis Rheum."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5733\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:52:20Z","timestamp":1760032340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5733"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,15]]},"references-count":86,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125733"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125733","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,15]]}}}