Developments in pharmacotherapeutic agents for hepatitis B - how close are we to a functional cure?

Hepatitis B virus (HBV) remains a public health concern given its global prevalence and potential complications including hepatocellular carcinoma (HCC). Current therapies, including nucleos(t)ide analogs (NA) and interferons (IFN), are effective in chronic treatment of HBV but rarely provide a functional cure due to inadequate host response and the presence of viral DNA. Therefore, novel therapies that enhance the innate immune response while suppressing DNA transcription may provide definitive treatment of HBV.

In this review, the authors provide a brief overview of commonly used agents and their efficacy in treatment of HBV. Newer therapies with direct antiviral agents such as bepirovirsen (antisense oligonucleotide (ASO)) and entry inhibitors such as bulevirtide have shown efficacy in reducing viral load but demonstrate further reductions in conjunction with immune modulators such as therapeutic vaccines.

Combination therapy is far superior to monotherapy alone, necessitating the need for both immunomodulators and direct antiviral agents in chronic treatment of HBV. Therapies that target covalently closed circular (cccDNA) with immunomodulators like therapeutic vaccines have shown promising results and may ultimately achieve functional cure. However, therapies need to be evaluated in the context of the patient, considering both financial and socioeconomic factors.