{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T16:54:21Z","timestamp":1793120061757,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The nuclear farnesoid X receptor (FXR) regulates bile acid homeostasis and is a drug target for metabolic liver diseases. FXR also plays an important role in hepatitis B virus (HBV) DNA transcription. <jats:italic>In vitro<\/jats:italic> and in mice, FXR agonist treatment leads to inhibition of viral replication and a decline in viral proteins, pregenomic RNA (pgRNA) and HBV DNA levels. We aimed to translate this to a clinical use by primarily evaluating the safety and secondary the anti\u2010viral effect of Vonafexor, a FXR agonist, in chronic hepatitis B (CHB) patients. In total, 73 CHB patients were enrolled in a two\u2010part Phase Ib double\u2010blind, placebo\u2010controlled trial. Patients were randomized to receive oral Vonafexor (100, 200 and 400\u00a0mg once daily, or 200\u00a0mg twice daily), placebo, or entecavir (Part A, <jats:italic>n<\/jats:italic>\u00a0=\u00a048) or to receive Vonafexor (300\u00a0mg once daily or 150\u00a0mg twice daily), or placebo, combined with pegylated\u2010interferon\u2010\u03b12a (Part B, <jats:italic>n<\/jats:italic>\u00a0=\u00a025) for 29\u00a0days. Patients were followed up for 35\u00a0days. Enrolled CHB patients were mostly HBeAg\u2010negative. Vonafexor was overall well tolerated and safe. The most frequent adverse events were moderate gastrointestinal events. Pruritus was more frequent with twice\u2010daily compared with once\u2010daily regimens (56%\u201367% vs. 16%, respectively, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Vonafexor monotherapy of 400\u00a0mg once daily decreased HBsAg concentrations (\u20130.1\u00a0log<jats:sub>10<\/jats:sub>\u00a0IU\/mL, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), and Vonafexor\/pegylated\u2010IFN\u2010\u03b12a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti\u2010viral effect the therapeutic potential of which has to be evaluated in larger trials.<\/jats:p>","DOI":"10.1111\/jvh.13608","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T08:55:00Z","timestamp":1630486500000},"page":"1690-1698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1067-0502","authenticated-orcid":false,"given":"Robin","family":"Erken","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam UMC University of Amsterdam Duivendrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-7395","authenticated-orcid":false,"given":"Patrice","family":"Andre","sequence":"additional","affiliation":[{"name":"Inserm U1111 CNRS UMR5308 Universit\u00e9 Lyon 1, and Ecole Normale Sup\u00e9rieure de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Roy","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-7754","authenticated-orcid":false,"given":"Neeltje","family":"Kootstra","sequence":"additional","affiliation":[{"name":"Amsterdam UMC University of Amsterdam Department of Experimental Immunology Amsterdam Infection &amp; Immunity Institute University of Amsterdam Amsterdam Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelie","family":"Barzic","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Girma","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Laveille","sequence":"additional","affiliation":[{"name":"Calvagone Liergues France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Radreau\u2010Pierini","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Darteil","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4963-5632","authenticated-orcid":false,"given":"Jacky","family":"Vonderscher","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4908-8608","authenticated-orcid":false,"given":"Pietro","family":"Scalfaro","sequence":"additional","affiliation":[{"name":"Enyo Pharma SA Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-8671","authenticated-orcid":false,"given":"Pisit","family":"Tangkijvanich","sequence":"additional","affiliation":[{"name":"Center of Excellence in Hepatitis and Liver Cancer Faculty of Medicine Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3394-1635","authenticated-orcid":false,"given":"Robert","family":"Flisiak","sequence":"additional","affiliation":[{"name":"Klinika Chor\u00f3b Zaka\u017anych I Hepatologii UMB Uniwersytecki Szpital Kliniczny w Bia\u0142ymstoku Bia\u0142ystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-9247","authenticated-orcid":false,"given":"Henk","family":"Reesink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Leiden University Medical Center Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,29]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO.Global hepatitis report World Health Organisation;2017."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(18)30056-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/v9060156"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2017.04.009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700330-JLR200"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.09.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27159"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02208-08"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-236372"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801181R"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201500134"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00883-08"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06742-11"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28924"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03478-13"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00010.2008"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01562-12"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02020-06"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.7.4238-4245.2005"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature17170"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/v8100281"},{"issue":"1","key":"e_1_2_10_24_1","article-title":"In vitro characterization of Eyp001 a novel, potent and selective FXR agonist entering phase 2 clinical trials in chronic hepatitis B","volume":"70","author":"Darteil R","year":"2019","journal-title":"Hepatology"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23716"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61933-4"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.01.047"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31205"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.08.033"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13223"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30344-9"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.03.050"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0241"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30346-2"},{"key":"e_1_2_10_35_1","first-page":"e921487\u20101","article-title":"Hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during peginterferon treatment","volume":"26","author":"Wang K","year":"2020","journal-title":"Med Sci Monit"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13608","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13608","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13608","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T08:36:12Z","timestamp":1693211772000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13608"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,29]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1111\/jvh.13608"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13608","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,29]]},"assertion":[{"value":"2021-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}