Summary
Introduction. Chronic hepatitis B virus infection remains a significant global health concern despite effective vaccination programs. Current treatment options, including nucleos(t)ide analogs and pegylated interferon alpha, fail to achieve complete viral eradication due to the persistence of covalently closed circular DNA (cccDNA) in hepatocytes. Consequently, the optimal therapeutic goal is considered a realistic functional cure, which is achieved in only a small proportion of treated patients. The limited efficacy of antiviral therapy has driven the development of novel therapeutic strategies aimed at enhancing viral replication control and immune system activation.
Methods. A literature search was conducted using the PubMed and Google Scholar databases. The search included key terms and their combinations: chronic hepatitis B, realistic functional cure, sterilizing cure, HBsAg clearance, antiviral therapy, direct-acting antiviral drugs, immune-targeting therapies. Only peer-reviewed scientific articles published within the last five years were analyzed.
Results. Ongoing clinical trials focus on both direct- acting antiviral drugs and host immune-modulating agents. Direct-acting antivirals include entry inhibitors, RNA interference therapy, targeting HBsAg expression, capsid assembly modulators, and nucleic acid polymers that inhibit viral replication. Immune- modulating agents, such as Toll-like receptor agonists, immune checkpoint inhibitors, therapeutic vaccines, and monoclonal antibodies, aim to enhance host-specific immune responses and promote the clearance of hepatitis B virus infected hepatocytes.
Conclusions. Clinical evidence suggests that combining novel and existing therapeutic approaches yields superior outcomes in chronic hepatitis B infection treatment compared to monotherapy with current antiviral agents. However, immune-modulating therapies may pose significant adverse effects, emphasizing the need for long-term clinical studies to evaluate their safety and optimize treatment regimens.
