Research advances with dozens of investigational agents being developed for treatment of chronic hepatitis B (CHB), including (1) direct-acting antivirals (DAAs) that interfere with a specific step in viral replication and (2) host-targeting agents that inhibit viral replication by modifying host cell function, provide hope that we may soon have a functional cure for CHB.

DAAs being developed include RNA interference therapies, covalently closed circular DNA (cccDNA) formation and transcription inhibitors, core/capsid inhibitors, reverse transcriptase inhibitors, hepatitis B surface antigen (HBsAg) release inhibitors, antisense oligonucleotides, and helioxanthin analogues.

Host-targeting agents being developed include entry inhibitors, cyclophilin inhibitors, and multiple immunomodulatory agents, including Toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, engineered T cells, recombinant human interleukin-7 (CYT107), and SB 9200.