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However, covalently closed circular <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> (ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>) of hepatitis B virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>) persists, resulting in viral relapse after the discontinuation of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To discuss and review novel therapies for chronic hepatitis B infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Recent published studies which searched from PubMed were comprehensive reviewed. The key words include chronic hepatitis B, hepatitis B virus cure, covalently closed circular <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>, direct acting anti\u2010virals and host targeting agents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several novel agents through viral and host targets approaches are under investigations towards functional cure of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>. On the one hand, direct acting anti\u2010virals targeting virus itself, such as <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> new polymerase inhibitor, entry inhibitor, engineered site\u2010specific nucleases and <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> interference, could inhibit amplification of ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> as well as intrahepatic <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> infection and eliminate or silence ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> transcription. Inhibitors of <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> nucleocapsid assembly suppress capsid formation and prevent synthesis of <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content>. On the other hand, host targeting agents (<jats:styled-content style=\"fixed-case\">HTA<\/jats:styled-content>) include lymphotoxin\u2010\u03b2 receptor agonist, toll\u2010like receptor agonist, immune checkpoint inhibitors and adenovirus\u2010based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce noncytolytic destruction of ccc<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> or attack <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>\u2010infected hepatocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>With these promising approaches, we hope to reach global <jats:styled-content style=\"fixed-case\">hepatitis B virus<\/jats:styled-content> control in the middle of this century.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13694","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T14:42:48Z","timestamp":1466001768000},"page":"213-222","source":"Crossref","is-referenced-by-count":52,"title":["Review article: novel therapies for hepatitis B virus cure \u2013 advances and 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