New strategies for the treatment of chronic hepatitis B

  • Trends Mol Med. 2022 Sep;28(9):742-757. doi: 10.1016/j.molmed.2022.06.002.
Lung-Yi Mak  1 ,  Ka-Shing Cheung  2 ,  James Fung  1 ,  Wai-Kay Seto  3 ,  Man-Fung Yuen  4
Affiliations
  • 1. Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong.
  • 2. Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • 3. Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • 4. Department of Medicine, School of Clinical Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong; State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong. Electronic address: [email protected].
PMID: 35780008 DOI: 10.1016/j.molmed.2022.06.002
Abstract

Functional cure, as defined by seroclearance of hepatitis B surface antigen (HBsAg), is the desired treatment endpoint for chronic hepatitis B (CHB) Infection, yet is rarely achieved with the currently approved therapy. Novel treatments currently in the clinical phase of development act by inhibiting viral replication/antigen reduction and/or by restoring host immune control. Although some agents are effective in reducing the viral antigen load, a greater magnitude of suppression is required to achieve functional cure. Compounds that target the covalently closed circular DNA (cccDNA) pool, hepatitis B X (HBx) protein inhibition, and mRNA destabilization are also in the preclinical phase of development. Challenges which remain include the clinical implications, immunological perturbations, and safety of these novel compounds to be used in the real-life setting.

Keywords
RNA interference; cccDNA; functional cure; gene editing; hepatitis B virus.
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