{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:47Z","timestamp":1786977947064,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T00:00:00Z","timestamp":1720051200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022M721473"],"award-info":[{"award-number":["2022M721473"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["iMeta"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Functional cure for chronic hepatitis B (CHB) remains challenging due to the lack of direct intervention methods for hepatic inflammation. Multi\u2010omics research offers a promising approach to understand hepatic inflammation mechanisms in CHB. A Bayesian linear model linked gene expression with clinical parameters, and population\u2010specific expression analysis (PSEA) refined bulk gene expression into specific cell types across different clinical phases. These models were integrated into our analysis of key factors like inflammatory cells, immune activation, T cell exhaustion, chemokines, receptors, and interferon\u2010stimulated genes (ISGs). Validation through multi\u2010immune staining in liver specimens from CHB patients bolstered our findings. In CHB patients, increased gene expression related to immune cell activation and migration was noted. Marker genes of macrophages, T cells, immune\u2010negative regulators, chemokines, and ISGs showed a positive correlation with serum alanine aminotransferase (ALT) levels but not hepatitis B virus DNA levels. The PSEA model confirmed T cells as the source of exhausted regulators, while macrophages primarily contributed to chemokine expression. Upregulated ISGs (\n                    <jats:italic>ISG20, IFI16, TAP2, GBP1, PSMB9<\/jats:italic>\n                    ) in the hepatitis phase were associated with T cell and macrophage infiltration and positively correlated with ALT levels. Conversely, another set of ISGs (\n                    <jats:italic>IFI44, ISG15, IFI44L, IFI6, MX1<\/jats:italic>\n                    ) mainly expressed by hepatocytes and B cells showed no correlation with ALT levels. Our study presents a multi\u2010omics analysis integrating bulk transcriptomic, single\u2010cell sequencing data, and clinical data from CHB patients to decipher the cause of intrahepatic inflammation in CHB. The findings confirm that macrophages secrete chemokines like CCL20, recruiting exhausted T cells into liver tissue; concurrently, hepatocyte innate immunity is suppressed, hindering the antiviral effects of ISGs.\n                  <\/jats:p>","DOI":"10.1002\/imt2.221","type":"journal-article","created":{"date-parts":[[2024,7,4]],"date-time":"2024-07-04T08:43:34Z","timestamp":1720082614000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cell\u2010type\u2010specific expression analysis of liver transcriptomics with clinical parameters to decipher the cause of intrahepatic inflammation in chronic hepatitis B"],"prefix":"10.1002","volume":"3","author":[{"given":"Jun","family":"Wang","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology Shenzhen China"},{"name":"Institute of Virology, University Hospital of Essen University of Duisburg\u2010Essen Essen Germany"},{"name":"Clinical Medical Research Center, The Fifth People's Hospital of Wuxi Jiangnan University Wuxi China"},{"name":"Bioinformatics and Computational Biophysics, Faculty of Biology and Center for Medical Biotechnology (ZMB) University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology Shenzhen China"},{"name":"Institute of Virology, University Hospital of Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwang","family":"Qiu","sequence":"additional","affiliation":[{"name":"Clinical Medical Research 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