{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:31:16Z","timestamp":1762867876434,"version":"3.40.5"},"reference-count":41,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T00:00:00Z","timestamp":1565654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic HBV infection results in various clinical manifestations due to different levels of immune response. In recent years, hepatitis B treatment has improved by long\u2010term administration of nucleos(t)ide analogues (NUCs) and peg\u2010interferon. Nucleic acid polymers (NAPs; REP 2139\u2010Ca and REP 2139\u2010Mg) are new antiviral drugs that block the assembly of subviral particles, thus preventing the release of HBsAg and allowing its clearance and restoration of functional control of infection when combined with various immunotherapies. In the REP 102 study (NCT02646189), 9 of 12 patients showed substantial reduction of HBsAg and seroconversion to anti\u2010HBs in response to REP 2139\u2010Ca, whereas 3 of 12 patients did not show responses (&gt;1\u00a0log reduction of HBsAg and HBV DNA from baseline). We characterized the dynamic changes of HBV quasispecies (QS) within the major hydrophilic region (MHR) of the \u2018pre\u2010S\/S\u2019 open reading frame including the \u2018a\u2019 determinant in responders and nonresponders of the REP 102 study and four untreated matched controls. HBV QS complexity at baseline varied slightly between responders and nonresponders (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.28). However, these responders showed significant decline in viral complexity (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) as REP 2139\u2010Ca therapy progressed but no significant change in complexity was observed among the nonresponders (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.99). The MHR mutations were more frequently observed in responders than in nonresponders and matched controls. No mutations were observed in \u2018a\u2019 determinant of major QS population which may interfere with the detection of HBsAg by diagnostic assays. No specific mutations were found within the MHR which could explain patients\u2019 poor HBsAg response during REP 2139\u2010Ca therapy.<\/jats:p>","DOI":"10.1111\/jvh.13180","type":"journal-article","created":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T22:24:31Z","timestamp":1563575071000},"page":"1454-1464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Kinetics of hepatitis B surface antigen quasispecies during REP 2139\u2010Ca therapy in HBeAg\u2010positive chronic HBV infection"],"prefix":"10.1111","volume":"26","author":[{"given":"Zainab","family":"Usman","sequence":"first","affiliation":[{"name":"Department of Bioinformatics Technische Universit\u00e4t M\u00fcnchen, Wissenschaftszentrum Weihenstephan Freising Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrvoje","family":"Mijo\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Virology Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi","family":"Karimzadeh","sequence":"additional","affiliation":[{"name":"Institute of Virology Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Department of Medicine II University Hospital Munich\u2010Grosshadern Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"D\u00e4umer","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Genetics Kaiserslautern Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamun","family":"Al\u2010Mathab","sequence":"additional","affiliation":[{"name":"Bangabandhu Sheikh Mujib Medical University Dhaka Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Bazinet","sequence":"additional","affiliation":[{"name":"Replicor Inc. 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