{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:54:23Z","timestamp":1784228063046,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic hepatitis B (CHB), driven by persistent hepatitis B virus (HBV) infection, is characterised by unresolved liver inflammation and fibrosis. Despite its clinical burden, the immune mechanisms underpinning CHB progression, particularly the role of macrophage polarisation, remain incompletely defined. We integrated multi\u2010modal approaches to dissect the CHB immune microenvironment: immunohistochemistry (HBsAg\/HBcAg quantification), imaging mass cytometry (spatial immune mapping), microfluidic high\u2010throughput qPCR (gene profiling) and MILLIPLEX assays (cytokine quantification). In\u00a0vitro, HBV\u2010producing HepG2.2.15 cells were cocultured with polarised THP\u20101 macrophages (M1\/M2) and LX\u20102 hepatic stellate cells (HSCs) to model macrophage\u2013HSCs crosstalk. CHB severity correlated with elevated virologic markers (HBsAg, HBeAg, HBV DNA) and liver injury indices (ALT\/AST). The hepatic immune landscape was dominated by M1\u2010like macrophages, which colocalised with activated HSCs and collagen\u2160+ fibrotic niches. Intrahepatic M1 markers (CD86, TNF\u03b1, CXCL9 and CXCR3) were upregulated, while the M2 marker IL\u201010 was suppressed. Serum HBeAg levels positively correlated with intrahepatic CD86 and CXCL9, implicating HBeAg as a key driver of M1 polarisation. Compartment\u2010specific cytokine profiling revealed elevated liver\u2010to\u2010plasma ratios of TGF\u2010\u03b1, IFN\u2010\u03b3 and IP\u201010 in advanced CHB, contrasting with reduced IL\u201010. In\u00a0vitro, HBV skewed THP\u20101 macrophages towards an M1 phenotype and HBV\u2010primed M1 macrophages potently activated LX\u20102 cells. Persistent HBV infection fuels CHB progression by fostering a pro\u2010inflammatory M1 macrophage\u2010dominated microenvironment, which synergises with HSCs activation and fibrogenesis. Our findings nominate M1 polarisation as therapeutic targets to disrupt inflammation\u2013fibrosis crosstalk in CHB.<\/jats:p>","DOI":"10.1111\/jvh.70052","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T12:40:48Z","timestamp":1752151248000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>M1<\/scp>\n                    \u2010Like Macrophage May Contribute to the Inflammation and Fibrosis Process of Chronic Hepatitis B"],"prefix":"10.1111","volume":"32","author":[{"given":"Yuxue","family":"Gao","sequence":"first","affiliation":[{"name":"Beijing Institute of Hepatology Beijing YouAn Hospital, Capital Medical University  Beijing China"},{"name":"Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer  Beijing 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Hepatitis and Liver Cancer  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dexi","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Institute of Hepatology Beijing YouAn Hospital, Capital Medical University  Beijing China"},{"name":"Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7214-1097","authenticated-orcid":false,"given":"Qiqi","family":"Ning","sequence":"additional","affiliation":[{"name":"Beijing Institute of Hepatology Beijing YouAn Hospital, Capital Medical University  Beijing China"},{"name":"Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer  Beijing 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