{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:05:30Z","timestamp":1770231930110,"version":"3.49.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2022,4,2]],"date-time":"2022-04-02T00:00:00Z","timestamp":1648857600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Nucleic acid polymers block the assembly of hepatitis B virus (HBV) subviral particles, effectively preventing hepatitis B surface antigen (HBsAg) replenishment in the circulation. Nucleic acid polymer (NAP)\u2013based combination therapy of HBV infection or HBV\/hepatitis D virus (HDV) co\u2010infection is accompanied by HBsAg clearance and seroconversion, HDV\u2010RNA clearance in co\u2010infection, and persistent functional cure of HBV (HBsAg &lt; 0.05 IU\/ml, HBV\u2010DNA target not dected, normal alanine aminotransferase) and persistent clearance of HDV RNA. An analysis of HBsAg isoform changes during quantitative HBsAg declines (qHBsAg), and subsequent treatment\u2010free follow\u2010up in the REP 301\/REP 301\u2010LTF (HBV\/HDV) and REP 401 (HBV) studies was conducted. HBsAg isoforms were analyzed from frozen serum samples using Abbott Research Use Only assays for HBsAg isoforms (large [L], medium [M], and total [T]). The relative change over time in small HBsAg relative to the other isoforms was inferred by the change in the ratio over time of T\u2010HBsAg to M\u2010HBsAg. HBsAg isoform declines followed qHBsAg declines in all participants. No HBsAg isoforms were detectable in any participants with functional cure. HBsAg declines &gt; 2 log<jats:sub>10<\/jats:sub> IU\/ml from baseline were correlated with selective clearance of S\u2010HBsAg in 39 of 42 participants. Selective S\u2010HBsAg decline was absent in 9 of 10 participants with HBsAg decline &lt; 2 log<jats:sub>10<\/jats:sub> IU\/ml from baseline. Mild qHBsAg rebound during follow\u2010up &lt;10 IU\/ml consisted mostly of S\u2010HBsAg and M\u2010HBsAg and not accompanied by significant covalently closed circular DNA activity. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> The faster observed declines in S\u2010HBsAg indicate the selective clearance of subviral particles from the circulation, consistent with previous mechanistic studies on NAPs. Trace HBsAg rebound in the absence of HBV DNA may reflect HBsAg derived from integrated HBV DNA and not rebound of viral infection.<\/jats:p>","DOI":"10.1002\/hep4.1951","type":"journal-article","created":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T05:46:05Z","timestamp":1648964765000},"page":"1870-1880","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":18,"title":["HBsAg isoform dynamics during NAP\u2010based therapy of HBeAg\u2010negative chronic HBV and HBV\/HDV infection"],"prefix":"10.1097","volume":"6","author":[{"given":"Michel","family":"Bazinet","sequence":"first","affiliation":[{"name":"Replicor Inc.,Montreal,Quebec,Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Anderson","sequence":"additional","affiliation":[{"name":"Abbott Diagnostics,Abbott 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Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Smesnoi","sequence":"additional","affiliation":[{"name":"Toma Ciorb\u01ce Infectious Clinical Hospital,Chi\u0219in\u0103u,Republic of Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatina","family":"Musteata","sequence":"additional","affiliation":[{"name":"Toma Ciorb\u01ce Infectious Clinical Hospital,Chi\u0219in\u0103u,Republic of Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Jucov","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases,Nicolae Testemi\u0163anu State University of Medicine and Pharmacy,Chi\u0219in\u0103u,Republic of Moldova"},{"name":"ARENSIA Exploratory Medicine,Republican Clinical Hospital,Chi\u0219in\u0103u,Republic of Moldova"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Institute for 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