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HBsAg increase was defined as either a \u22655% increase from baseline to week 208 or at least two \u22655% increases between consecutive available visits. A subset of 10 patients with serial liver RNA sequencing underwent integrated clinical, transcriptomic, and histopathological analyses. HBV-host chimeric transcripts were identified using\n                      <jats:italic>ChimericSeq<\/jats:italic>\n                      and verified by BLAST, and intrahepatic HBsAg was assessed by immunohistochemistry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall, 31.8% (99\/311) of patients met the criteria for HBsAg increase, while others were classified into the stable\/decrease group. Lower baseline HBsAg and higher histologic activity index (HAI) were independently associated with HBsAg increase (both\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). In the serial-biopsy subset (\n                      <jats:italic>n<\/jats:italic>\n                      = 10), patients in the HBsAg increase group (4\/4) showed increased HBV-host chimeric transcript burden at week 260 versus week 78, whereas the six patients in the stable\/decrease group showed stable or reduced burden. Intrahepatic HBsAg immunohistochemistry showed persistent clustered cytoplasmic positivity, with transcriptomic analysis indicating downregulation of multiple immune-related pathways in the HBsAg increase group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>About 31.8% of patients had HBsAg increase during antiviral therapy. Baseline HBsAg and HAI were associated with HBsAg increase during antiviral therapy. In the exploratory serial-biopsy subset, patients with HBsAg increase tended to exhibit an increase in transcriptionally active HBV-host chimeric transcript burden and persistent clustered cytoplasmic HBsAg positivity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-026-11154-9","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:50:44Z","timestamp":1791456644000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploratory analysis of transcriptionally active HBV-host chimeric transcript burden in patients with increasing HBsAg during long-term antiviral therapy"],"prefix":"10.1007","author":[{"given":"Luqi","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yameng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiwen","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoning","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9409-1158","authenticated-orcid":false,"given":"Hong","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"6","key":"11154_CR1","first-page":"1425","volume":"11","author":"H You","year":"2023","unstructured":"You H, Wang F, Li T, Xu X, Sun Y, Nan Y, et al. 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