New strategies for the treatment of chronic hepatitis B

Functional cure, as defined by seroclearance of hepatitis B surface antigen (HBsAg), is the desired treatment endpoint for chronic hepatitis B (CHB) infec-tion, 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 inhibi-tion, and mRNA destabilization are also in the preclinical phase of development. Challenges which remain include the clinical implications, immunological pertur-bations, and safety of these novel compounds to be used in the real-life setting.