{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:49Z","timestamp":1790753809886,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T00:00:00Z","timestamp":1668124800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background\/Aims<\/jats:title>\n                    <jats:p>Novel agents acting against hepatitis B virus (HBV) are needed to improve HBsAg seroclearance or termed as \u2018functional cure\u2019. Inarigivir (retinoic acid\u2010inducible gene I agonist) has immunomodulatory and direct antiviral actions against HBV. We aimed to determine the safety and efficacy of Inarigivir for the treatment of HBV infection.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients\/Methods<\/jats:title>\n                    <jats:p>80 treatment\u2010na\u00efve patients were randomized in 4 ascending dose cohorts to receive 12\u2009weeks of Inarigivir 25, 50, 100, 200\u2009mg or placebo in a ratio of 4:1. All patients were then given tenofovir for another 12\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Least squares (LS) mean reductions in HBV DNA from baseline increased with higher doses of Inarigivir (0.6116 in 25\u2009mg and 1.5774 in 200\u2009mg groups vs. 0.0352 in placebo group) (95% CI 0.9518\u20130.2011 and 1.921\u20131.1634 respectively). LS mean changes in HBV RNA and HBsAg from baseline ranged from \u22120.3856 to \u22120.5794 versus \u22120.1474 and \u22120.0956 to \u22120.1818 versus +0.0026 in Inarigivir\u2010treated versus placebo groups respectively. During the tenofovir\u2010treated period, LS mean reductions in HBsAg in the Inarigivir\u2010treated groups ranged from 0.1709 to 0.3529 versus 0.1984 in the placebo group. Inarigivir\u2010treated groups showed mean reductions in ALT from baseline between 23.3 and 33.8 versus 0.7\u2009U\/L in the placebo group. Treatment\u2010emergent adverse events related to Inarigivir and placebo occurred in 4.7% and 6.3% patients respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Twelve\u2010week Inarigivir up to 200\u2009mg dose was associated with a reduction of HBV DNA, HBV RNA and antigen levels. A trend for greater HBsAg reduction was observed in Inarigivir pre\u2010treated patients after switching to tenofovir.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15465","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T06:44:17Z","timestamp":1666853057000},"page":"77-89","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A phase 2, open\u2010label, randomized, multiple\u2010dose study evaluating Inarigivir in treatment\u2010na\u00efve patients with chronic hepatitis B"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-7725","authenticated-orcid":false,"given":"Man\u2010Fung","family":"Yuen","sequence":"first","affiliation":[{"name":"Department of Medicine &amp; State Key Laboratory of Liver Research, Queen Mary Hospital, School of Clinical Medicine The University of Hong Kong  Pok Fu Lam Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Ditmanson Medical Foundation Chiayi Christian Hospital  Chiayi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun\u2010Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Hepatitis Research Center National Taiwan University College of Medicine and Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3706-1259","authenticated-orcid":false,"given":"Wen\u2010Juei","family":"Jeng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center Chang Gung University  Taoyuan City Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdy","family":"Elkhashab","sequence":"additional","affiliation":[{"name":"Toronto Liver Centre, North York General Hospital University of Toronto  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1472-0901","authenticated-orcid":false,"given":"Carla S.","family":"Coffin","sequence":"additional","affiliation":[{"name":"Cumming School of Medicine University of Calgary  Calgary Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2926-1007","authenticated-orcid":false,"given":"Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine Seoul Metropolitan Government Boramae Medical Center Seoul  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Greenbloom","sequence":"additional","affiliation":[{"name":"Toronto Digestive Disease Associates  Woodbridge Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-8767","authenticated-orcid":false,"given":"Alnoor","family":"Ramji","sequence":"additional","affiliation":[{"name":"Gastrointestinal Research Institute  Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-577X","authenticated-orcid":false,"given":"Young S.","family":"Lim","sequence":"additional","affiliation":[{"name":"Asan Medical Center University of Ulsan College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-1170","authenticated-orcid":false,"given":"Yoon J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Liver Research Institute Seoul National University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott K.","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Toronto Toronto General Hospital  Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-1500","authenticated-orcid":false,"given":"Dong J.","family":"Kim","sequence":"additional","affiliation":[{"name":"Hallym University College of Medicine  Chuncheon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3255-8474","authenticated-orcid":false,"given":"Jeong\u2010Won","family":"Jang","sequence":"additional","affiliation":[{"name":"Seoul St. Mary's Hospital The Catholic University of Korea  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan Sik","family":"Lee","sequence":"additional","affiliation":[{"name":"Gangnam Severance Hospital Yonsei University Health System  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhakrishnan P.","family":"Iyer","sequence":"additional","affiliation":[{"name":"RIGImmune, Inc.  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Macfarlane","sequence":"additional","affiliation":[{"name":"Spring Bank Pharmaceuticals  Hopkinton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0507-678X","authenticated-orcid":false,"given":"Kathy","family":"Jackson","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen A.","family":"Locarnini","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital, The Peter Doherty Institute for Infection and Immunity  Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-1611","authenticated-orcid":false,"given":"Henry L. Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics The Chinese University of Hong Kong, Prince of Wales Hospital  Sha Tin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nezam H.","family":"Afdhal","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Interim Guidance for Country Validation of Viral Hepatitis Elimination","author":"WHO","year":"2021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6728a2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31865-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2018.35"},{"issue":"72","key":"e_1_2_9_6_1","first-page":"539","article-title":"EASL\u2010AASLD HBV treatment endpoints conference faculty. Guidance for design and endpoints of clinical trials in chronic hepatitis B \u2010 report from the 2019 EASL\u2010AASLD HBV treatment endpoints conference","volume":"2020","author":"Cornberg M","year":"2019","journal-title":"J Hepatol"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.07.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-305517"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-019-09998-5"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.12.016"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169631"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(15)30194-X"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27381"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","unstructured":"AgarwalK AfdhalN CoffinCS et al.Liver toxicity in the Phase 2 Catalyst 206 trial of inarigivir 400 mg daily added to a nucleos(t)ide in HBeAg negative patients. Annual meeting of European Association for the Study of Liver Disease The Digital International Liver Congress 2020 Late Breaker Abstract.","DOI":"10.1016\/S0168-8278(20)30766-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01780-5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ctg.2017.51"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31616"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2008.02.007"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15465","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.15465","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15465","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:30:52Z","timestamp":1771331452000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15465"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,11]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1111\/liv.15465"],"URL":"https:\/\/doi.org\/10.1111\/liv.15465","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,11]]},"assertion":[{"value":"2022-06-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}