{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:33Z","timestamp":1790753793116,"version":"4.1.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>GS\u20109688 (selgantolimod) is an oral selective small molecule agonist of toll\u2010like receptor 8 in clinical development for the treatment of chronic hepatitis B. In this study, we evaluated the antiviral efficacy of GS\u20109688 in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B virus.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>WHV\u2010infected woodchucks received eight weekly oral doses of vehicle, 1\u00a0mg\/kg GS\u20109688, or 3\u00a0mg\/kg GS\u20109688. Vehicle and 1\u00a0mg\/kg GS\u20109688 had no antiviral effect, whereas 3\u00a0mg\/kg GS\u20109688 induced a &gt;5 log<jats:sub>10<\/jats:sub> reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of detection in half of the treated woodchucks. In these animals, the antiviral response was maintained until the end of the study (&gt;5\u00a0months after the end of treatment). GS\u20109688 treatment reduced intrahepatic WHV RNA and DNA levels by &gt;95% in animals in which the antiviral response was sustained after treatment cessation, and these woodchucks also developed detectable anti\u2010WHsAg antibodies. The antiviral efficacy of weekly oral dosing with 3\u00a0mg\/kg GS\u20109688 was confirmed in a second woodchuck study. The antiviral response to GS\u20109688 did not correlate with systemic GS\u20109688 or cytokine levels but was associated with transient elevation of liver injury biomarkers and enhanced proliferative response of peripheral blood mononuclear cells to WHV peptides. Transcriptomic analysis of liver biopsies taken prior to treatment suggested that T follicular helper cells and various other immune cell subsets may play a role in the antiviral response to GS\u20109688.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Finite, short\u2010duration treatment with a clinically relevant dose of GS\u20109688 is well tolerated and can induce a sustained antiviral response in WHV\u2010infected woodchucks; the identification of a baseline intrahepatic transcriptional signature associated with response to GS\u20109688 treatment provides insights into the immune mechanisms that mediate this antiviral effect.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31255","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T04:13:26Z","timestamp":1585973606000},"page":"53-67","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":63,"title":["Toll\u2010Like Receptor 8 Agonist GS\u20109688 Induces Sustained Efficacy in the Woodchuck Model of Chronic Hepatitis B"],"prefix":"10.1097","volume":"73","author":[{"given":"Stephane","family":"Daffis","sequence":"first","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Balsitis","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster City,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc.,Foster 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