{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:17:02Z","timestamp":1790810222013,"version":"4.1.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8<jats:sup>+<\/jats:sup> T-cell response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8<jats:sup>+<\/jats:sup> T-cell response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation\/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8<jats:sup>+<\/jats:sup> cell effector function were correlated with HBsAg level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8<jats:sup>+<\/jats:sup> T-cell proliferation against at least two HBV epitopes was higher in HBsAg &amp;lt; 1,000 IU\/ml group. CD8<jats:sup>+<\/jats:sup> T-cell expansion after HBVpolymerase<jats:sub>456-63<\/jats:sub>-specific stimulation was impaired in HBsAg &amp;gt; 1,000 IU\/ml group, while the response against HBVcore<jats:sub>18-27<\/jats:sub> was preserved and response against envelope<jats:sub>183-91<\/jats:sub> was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase<jats:sub>456-63<\/jats:sub> CD8<jats:sup>+<\/jats:sup> cell response had lower LS\/duration of infection and APRI\/duration of infection rates. HBV-polymerase<jats:sub>456-63<\/jats:sub>-specific CD8<jats:sup>+<\/jats:sup> T-cell proliferation intensity was negatively correlated with LS\/years of infection ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HBsAg &amp;gt; 1,000 IU\/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8<jats:sup>+<\/jats:sup> T-cell response.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1352929","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:52:38Z","timestamp":1710319958000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["HBsAg level defines different clinical phenotypes of HBeAg(\u2212) chronic HBV infection related to HBV polymerase-specific CD8+ cell response 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