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) 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.