Newer Therapies in HBV

• Complex hepatitis B virus (HBV) life cycle and current treatment are dependent on nucleos(t)ide analogues (NAs).
• A partial or functional cure is not enough, hence is crucial to target covalently covalently closed circular DNA (cccDNA) for a complete cure.
• Entry inhibitors are approved for chronic HDV, however, they do not address cccDNA.
• Attractive options for targeting cccDNA are – Inhibition of mini chromosomes and silencing transcription. Concerns over genomic stability are still hindrances.
• Post-transcriptional control – Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). Do not eliminate cccDNA, rebound post-treatment.
• Capsid assembly modulators (CAMs) are the best among the present novel therapies. They cause long-term suppression of HBV DNA and RNA.
• S-antigen transport-inhibiting oligonucleotide polymers (STOPS) and nucleic acid polymers (NAPs) have given promising results, however, need further studies.
• Good results have been obtained for TLR7, the combination of RIG with IFN, and promising results of vaccination in the phase III trial.
• Multiple combination strategies under investigation need larger and longer trials.