{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:35:44Z","timestamp":1789720544919,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2017,1,3]],"date-time":"2017-01-03T00:00:00Z","timestamp":1483401600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although current oral antivirals can maintain viral suppression and reduce the risk of liver\u2010related complications, lifelong therapy is associated with high cost, risk of breakthrough and potential toxicity. There is a need to develop a finite course of treatment which can provide sustained off\u2010treatment virological and clinical response. The likely marker of such a clinical <jats:styled-content style=\"fixed-case\">HBV CURE<\/jats:styled-content> would be <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>sAg clearance, but in addition ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> elimination would be required to prevent future reactivation (ie complete <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> cure). Chronic <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> infection is characterised by high viral and antigen burden and inadequate host immune responses, both of which will need to be overcome to achieve <jats:styled-content style=\"fixed-case\">HBV CURE<\/jats:styled-content>. Innovative approaches to restore innate and adaptive immune responses against <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> currently in clinical development include therapeutic vaccines, <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20107 and <jats:styled-content style=\"fixed-case\">TLR<\/jats:styled-content>\u20108 agonists. In future, strategies to reverse T\u2010cell exhaustion such as checkpoint inhibitors may be feasible. Currently, the only antivirals in clinical use are the <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> polymerase inhibitors. However, many other steps of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> virion life cycle can be targeted by small molecules, including inhibitors of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> entry, nucleocapsid formation and virion assembly and release. si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>s could inhibit many different steps by blocking multiple <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> transcripts. But, the ultimate goal will be to successfully eradicate or silence ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>. It is likely that successful <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> cure will require combination of immunomodulatory, antiviral and ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> silencing strategies. Efficacy, safety, route of administration and cost will ultimately determine the impact of these new regimens on the burden of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/liv.13304","type":"journal-article","created":{"date-parts":[[2017,1,13]],"date-time":"2017-01-13T04:15:37Z","timestamp":1484280937000},"page":"40-44","source":"Crossref","is-referenced-by-count":66,"title":["Future anti\u2010<scp>HBV<\/scp> strategies"],"prefix":"10.1111","volume":"37","author":[{"given":"Edward J.","family":"Gane","sequence":"first","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22295"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1573"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00028-9"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.09.072"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.07.027"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.016"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.003"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.037"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.01.010"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-010-0233-1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003856"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.030"},{"issue":"2","key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"S285","DOI":"10.1016\/S0168-8278(16)00590-0","article-title":"Achievement of surface antigen clearance in the liver by combination therapy with REP 2139\u2010CA and nucleoside analogues against chronic hepatitis B","volume":"64","author":"Quinet J","year":"2016","journal-title":"J Hepatol"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1513803112"},{"key":"e_1_2_12_16_1","first-page":"19","article-title":"Phase 1a safety and pharmacokinetics of NVR 3\u2013778, a potential first\u2010in\u2010class HBV core inhibitor","volume":"60","author":"Gane EJ","year":"2014","journal-title":"Hepatology"},{"key":"e_1_2_12_17_1","first-page":"385A","article-title":"Phase 1b efficacy and safety of NVR 3\u2013778, a first\u2010in\u2010class HBV core inhibitor, in HBeAg\u2010positive patients with chronic HBV infection","volume":"62","author":"Yuen MF","year":"2015","journal-title":"Hepatology"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(16)00626-7"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(16)00606-1"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230601"},{"key":"e_1_2_12_21_1","first-page":"10833","article-title":"CRISPR\/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus","volume":"5","author":"Ramanam V","year":"2015","journal-title":"Nature"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2014.38"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30204-3"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.13304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.13304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:39:30Z","timestamp":1694659170000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.13304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1]]},"references-count":22,"journal-issue":{"issue":"S1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1111\/liv.13304"],"URL":"https:\/\/doi.org\/10.1111\/liv.13304","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1]]}}}