Review article: novel therapies for hepatitis B virus cure – advances and perspectives
Journal
Alimentary Pharmacology and Therapeutics
Journal Volume
44
Journal Issue
3
Pages
213-222
Date Issued
2016
Author(s)
Lin C.-L.
Abstract
Background: Current anti-viral therapies, interferon and nucleos(t)ide analogues, have been proven to reduce the progression of chronic hepatitis B (CHB). However, covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) persists, resulting in viral relapse after the discontinuation of treatment. Aim: To discuss and review novel therapies for chronic hepatitis B infection. Methods: Recent published studies which searched from PubMed were comprehensive reviewed. The key words include chronic hepatitis B, hepatitis B virus cure, covalently closed circular DNA, direct acting anti-virals and host targeting agents. Results: Several novel agents through viral and host targets approaches are under investigations towards functional cure of HBV. On the one hand, direct acting anti-virals targeting virus itself, such as HBV new polymerase inhibitor, entry inhibitor, engineered site-specific nucleases and RNA interference, could inhibit amplification of cccDNA as well as intrahepatic HBV infection and eliminate or silence cccDNA transcription. Inhibitors of HBV nucleocapsid assembly suppress capsid formation and prevent synthesis of HBV DNA. On the other hand, host targeting agents (HTA) include lymphotoxin-β receptor agonist, toll-like receptor agonist, immune checkpoint inhibitors and adenovirus-based therapeutic vaccine. Through enhancing innate and adaptive immune responses, these agents could induce noncytolytic destruction of cccDNA or attack HBV-infected hepatocytes. Conclusion: With these promising approaches, we hope to reach global hepatitis B virus control in the middle of this century. ? 2016 John Wiley & Sons Ltd
SDGs
Other Subjects
alpha interferon; antiretrovirus agent; arc 520; at 130; at 61; bay 41 4109; besifovir; ccc 0346; ccc 0975; CD8 antigen; CRISPR associated protein; dv 601; entecavir; gs 4774; hepatitis B(e) antigen; lymphotoxin beta receptor agonist; nvr 1221; organic anion transporter 1; organic anion transporter 3; peginterferon alpha; programmed death 1 ligand 1; tenofovir alafenamide; tenofovir disoproxil; tg 1050; toll like receptor; toll like receptor 7; transcription activator like effector nuclease; unclassified drug; unindexed drug; vesatolimod; zinc finger nuclease; adaptive immunity; chronic hepatitis B; clinical effectiveness; concentration response; CRISPR Cas system; disease control; drug safety; gene amplification; gene expression; gene silencing; genetic transcription; Hepatitis B virus; human; innate immunity; long term care; nonhuman; phase 1 clinical trial (topic); phase 2 clinical trial (topic); phase 3 clinical trial (topic); practice guideline; priority journal; remission; Review; RNA interference; seroconversion; treatment response; virus capsid; virus replication
Publisher
Blackwell Publishing Ltd
Type
review