{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T18:37:41Z","timestamp":1793644661921,"version":"4.5.1"},"reference-count":28,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T00:00:00Z","timestamp":1655683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["205670"],"award-info":[{"award-number":["205670"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","journal-of-hepatology.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Hepatology"],"published-print":{"date-parts":[[2022,10]]},"DOI":"10.1016\/j.jhep.2022.05.031","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T21:51:41Z","timestamp":1655243501000},"page":"967-977","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":56,"title":["Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy"],"prefix":"10.1016","volume":"77","author":[{"given":"Man-Fung","family":"Yuen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong","family":"Heo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Kumada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyasu","family":"Karino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Chayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michio","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy Y.","family":"Lao-Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seng Gee","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Hwan","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kurosaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Jae","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalinee Eternity","family":"Labio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajneesh","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Oh","family":"Kweon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung Joon","family":"Yim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Cremer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Elston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Davies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Baptiste-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Paff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhep.2022.05.031_bib1","unstructured":"World Health Organization. Hepatitis B Key Facts. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b. Accessed: 25 March,\u00a02021."},{"key":"10.1016\/j.jhep.2022.05.031_bib2","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","year":"2017","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib3","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.031_bib4","unstructured":"World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. https:\/\/www.who.int\/hiv\/pub\/hepatitis\/hepatitis-b-guidelines\/en\/. Accessed: 15 April,\u00a02020."},{"key":"10.1016\/j.jhep.2022.05.031_bib5","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jhep.2019.11.003","article-title":"Guidance for design and endpoints of clinical trials in chronic hepatitis B - Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference(\u2021)","volume":"72","author":"Cornberg","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib6","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1002\/hep.29323","article-title":"Hepatitis B cure: from discovery to regulatory approval","volume":"66","author":"Lok","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.031_bib7","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1016\/j.jhep.2014.11.031","article-title":"Incidence of hepatocellular carcinoma after HBsAg seroclearance in chronic hepatitis B patients: a need for surveillance","volume":"62","author":"Kim","year":"2015","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib8","article-title":"New approaches to the treatment of chronic hepatitis B","volume":"9","author":"Alexopoulou","year":"2020","journal-title":"J\u00a0Clin Med"},{"key":"10.1016\/j.jhep.2022.05.031_bib9","series-title":"United States: Isis Pharmaceuticals, Inc.","first-page":"381","article-title":"Modulation of hepatitis B virus (HBV) expression","author":"Swayze","year":"2014"},{"key":"10.1016\/j.jhep.2022.05.031_bib10","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jhep.2020.04.013","article-title":"Hepatitis B surface antigen seroclearance: immune mechanisms, clinical impact, importance for drug development","volume":"73","author":"Tout","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib11","series-title":"The international HBV meeting of the molecular biology of hepatitis B viruses; Seoul, Republic of Korea; September 21\u201324, 2016","article-title":"Preclinical evaluation of 5\u2019-N-acetylgalactosamine (GalNAc) conjugated anti-sense oligonucleotides (ASO) against HBV in primary human hepatocytes and HBV transgenic mice","author":"You","year":"2016"},{"key":"10.1016\/j.jhep.2022.05.031_bib12","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/cpdd.670","article-title":"A\u00a0randomized, double-blind, placebo-controlled, first-time-in-human study to assess the safety, tolerability, and pharmacokinetics of single and multiple ascending doses of GSK3389404 in healthy subjects","volume":"8","author":"Han","year":"2019","journal-title":"Clin Pharmacol Drug Dev"},{"key":"10.1016\/j.jhep.2022.05.031_bib13","series-title":"Conference of the Asian Pacific association for the study of the liver; Manila, Philippines","article-title":"RNA interference (RNAi) in chronic hepatitis B (CHB): data from phase 2 study with JNJ-3989","author":"Gane","year":"2019"},{"key":"10.1016\/j.jhep.2022.05.031_bib14","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1093\/nar\/gku531","article-title":"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice","volume":"42","author":"Prakash","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.jhep.2022.05.031_bib15","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1080\/17425255.2019.1621838","article-title":"Pharmacokinetics and clinical pharmacology considerations of GalNAc3-conjugated antisense oligonucleotides","volume":"15","author":"Wang","year":"2019","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1016\/j.jhep.2022.05.031_bib16","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1002\/hep.31920","article-title":"Clinical study of single-stranded oligonucleotide RO7062931 in healthy volunteers and patients with chronic hepatitis B","volume":"74","author":"Gane","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.031_bib17","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1038\/s41591-021-01513-4","article-title":"Safety, tolerability and antiviral activity of the antisense oligonucleotide bepirovirsen in patients with chronic hepatitis B: a phase 2 randomized controlled trial","volume":"27","author":"Yuen","year":"2021","journal-title":"Nat Med"},{"key":"10.1016\/j.jhep.2022.05.031_bib18","doi-asserted-by":"crossref","first-page":"S50","DOI":"10.1016\/S0168-8278(20)30647-4","article-title":"Preliminary safety and antiviral activity of VIR-2218, an X-targeting HBV RNAi therapeutic, in chronic hepatitis B patients","volume":"73","author":"Gane","year":"2020","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib19","first-page":"1390A","article-title":"Efficacy and safety of the siRNA JNJ-3989 and\/OR the Capsid Assembly Modulator (CAM) JNJ-6379 for the treatment of chronic hepatitis B virus infection (CHB): results from the phase 2B REEF-1 study","volume":"74","author":"Yuen","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.031_bib20","first-page":"1402A","article-title":"Low HBsAg levels maintained following cessation of the GALNAC-siRNA, AB-729, in chronic hepatitis B subjects on nucleos(T)IDE analogue therapy","volume":"74","author":"Yuen","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.jhep.2022.05.031_bib21","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1111\/liv.13716","article-title":"ALT flares during nucleotide analogue therapy are associated with HBsAg loss in genotype A HBeAg-positive chronic hepatitis B","volume":"38","author":"Wong","year":"2018","journal-title":"Liver Int"},{"key":"10.1016\/j.jhep.2022.05.031_bib22","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1016\/j.cgh.2019.02.005","article-title":"Association Between Severe Serum Alanine Aminotransferase Flares and Hepatitis B e Antigen Seroconversion and HBV DNA Decrease in Untreated Patients With Chronic HBV Infection","volume":"17","author":"Brahmania","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib23","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.jhep.2014.08.033","article-title":"Hepatitis B flares in chronic hepatitis B: pathogenesis, natural course, and management","volume":"61","author":"Chang","year":"2014","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhep.2022.05.031_bib24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0187574","article-title":"Assessing single-stranded oligonucleotide drug-induced effects in\u00a0vitro reveals key risk factors for thrombocytopenia","volume":"12","author":"Sewing","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.jhep.2022.05.031_bib25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/nat.2016.0650","article-title":"The\u00a0effects of 2'-O-methoxyethyl containing antisense oligonucleotides\u00a0on platelets in human clinical trials","volume":"27","author":"Crooke","year":"2017","journal-title":"Nucleic Acid Ther"},{"key":"10.1016\/j.jhep.2022.05.031_bib26","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1182\/blood.V92.5.1617","article-title":"Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex","volume":"92","author":"Sheehan","year":"1998","journal-title":"Blood"},{"key":"10.1016\/j.jhep.2022.05.031_bib27","doi-asserted-by":"crossref","first-page":"4980","DOI":"10.1021\/bi002396x","article-title":"Phosphorothioate oligonucleotides inhibit the intrinsic tenase complex by an allosteric mechanism","volume":"40","author":"Sheehan","year":"2001","journal-title":"Biochemistry"},{"key":"10.1016\/j.jhep.2022.05.031_bib28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1124\/jpet.114.219378","article-title":"Mechanistic understanding for the greater sensitivity of monkeys to antisense oligonucleotide-mediated complement activation compared with humans","volume":"351","author":"Shen","year":"2014","journal-title":"J\u00a0Pharmacol Exp Ther"}],"container-title":["Journal of Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822003518?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168827822003518?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:55:50Z","timestamp":1777510550000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168827822003518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10]]},"references-count":28,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["S0168827822003518"],"URL":"https:\/\/doi.org\/10.1016\/j.jhep.2022.05.031","relation":{},"ISSN":["0168-8278"],"issn-type":[{"value":"0168-8278","type":"print"}],"subject":[],"published":{"date-parts":[[2022,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy","name":"articletitle","label":"Article Title"},{"value":"Journal of Hepatology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhep.2022.05.031","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver.","name":"copyright","label":"Copyright"}]}}