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New hepatitis B treatments aim for a cure by targeting viral replication and reducing HBsAg levels. While progress is being made, a complete cure for hepatitis B remains a significant challenge.

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Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Hepatitis B virus (HBV) treatments are evolving, with first- and second-generation therapies under evaluation for a cure.
  • Achieving a cure for hepatitis B, even defined by HBsAg seroclearance, presents a significant challenge.
  • A functional cure is accepted, while a partial functional cure involves reducing HBsAg levels after treatment.

Purpose of the Study:

  • To explore novel therapeutic strategies for achieving a cure for hepatitis B.
  • To investigate methods for deeper inhibition of HBV replication and reduction of HBsAg presentation.
  • To assess the potential of immunomodulatory therapies in conjunction with antiviral treatments.

Main Methods:

  • Evaluating combined therapies, such as capsid inhibitors with nucleoside analogues, for enhanced HBV replication suppression.
  • Investigating strategies to reduce hepatitis B surface antigen (HBsAg) presentation for seroclearance.
  • Exploring advancements in immunomodulatory therapies and novel experimental approaches.

Main Results:

  • Phase 2 studies show promising on-treatment reductions and HBsAg seroclearance, surpassing previous methods.
  • Antiviral therapy advancements have shown more progress than immunomodulatory approaches.
  • New treatments demonstrate improved efficacy in reducing viral load and HBsAg levels.

Conclusions:

  • Enhancing the immune response in hepatitis B may be more feasible after reducing the host antigen burden.
  • Experimental strategies like CRISPR-Cas9 gene editing and monoclonal antibodies offer potential for targeting cccDNA and viral components.
  • Further research into combined antiviral and immunomodulatory approaches is crucial for a hepatitis B cure.