{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T08:11:42Z","timestamp":1771920702503,"version":"3.50.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background and aims<\/jats:title>\n                    <jats:p>Hepatitis B virus (HBV) causes chronic hepatic infection, leading to various advanced liver diseases. Currently, there is still a lack of effective non-invasive biomarkers for evaluating hepatic inflammation and fibrosis. Circulating microRNAs (miRNAs) serve as key regulators and potential biomarkers in the progression and pathogenesis of HBV-associated progressive liver diseases. Here, we characterized the miRNA profile in chronic hepatitis B (CHB) patients and probed their association with liver inflammation and fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approaches and results<\/jats:title>\n                    <jats:p>We profiled 34 candidate miRNAs in serum from a well-characterized HBV Disease Continuum Cohort, comprising 165 individuals in the discovery set (42 healthy controls, HC; 40 CHB; 42 cirrhosis; 41 hepatocellular carcinomas, HCC) and 143 in an independent testing set. Serum miRNA levels were quantified by qRT-PCR. Supervised clustering and correlation analyses revealed distinct miRNA expression profiles across disease stages. Statistical analyses included logistic regression, and ROC\/AUC evaluation with 5-fold cross-validation and external validation. Unsupervised clustering and correlation with histological G\/S staging revealed stage-specific miRNA signatures: miR-224-5p, miR-125a-5p, and miR-15a-5p peaked in cirrhosis and strongly correlated with fibrosis stage (miR-224-5p: r = 0.606, p = 1.5E-12), while miR-200a-3p and miR-939-5p were predominantly upregulated in HCC. Critically, miR-224-5p emerged as a robust non-invasive biomarker for cirrhosis, with exceptional diagnostic accuracy (AUC\u00a0=\u00a00.973 in discovery; 0.906 in external validation), significantly outperforming APRI (0.803) and FIB-4 (0.809), and remained the sole independent predictor in multivariable analysis (p = 0.009). For HCC detection, the miR-200a-3p\/AFP combined model achieved outstanding performance (AUC &amp;gt; 0.9), substantially improving upon AFP alone (0.737). Bioinformatic prediction of targets (297 for miR-224-5p; 616 for miR-200a-3p) highlighted associated in cancer- and senescence-related pathways; however, these associations are in silico and require experimental validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We identify miR-224-5p as a fibroinflammatory activity indicator for early cirrhosis detection and miR-200a-3p as a synergistic enhancer of AFP for non-invasive HCC diagnosis, establishing a dual miRNA signature that spans the HBV disease continuum and addresses critical gaps in current risk stratification. These findings highlight the potential of specific serum miRNAs as non-invasive biomarkers for monitoring disease progression and improving the differential diagnosis during the process of HBV-related liver diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1671149","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T06:30:55Z","timestamp":1765434655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of serum MicroRNAs associated with hepatic immunoinflammatory injury in chronic hepatitis B: implications for non-invasive diagnosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengkui","family":"Han","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]},{"name":"Department of General Surgery, The 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University","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanwu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, Jiangsu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University","place":["Suzhou, Jiangsu, 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