Review new challenges and opportunities

Opportunities and challenges in curing hepatitis B.


The specificities of the HBV cycle that favor the development of chronic infection (middle), the clinical challenges posed by these biological features (top), and the opportunities currently being developed to achieve HBV cure goals (bottom). cccDNA, covalently closed circular DNA; 3D, three-dimensional; DC, dendritic cells; FNA, fine needle aspiration; HBe, hepatitis B e; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; MP , macrophages; NUC, nucleos

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Photo credit: Armando Andres Roca Suarez and Fabien Zoulim

Hepatitis B virus (HBV) is a major public health problem, with more than 296 million people worldwide being chronically infected. Although safe and effective vaccines have been available for more than 40 years, HBV remains a leading cause of liver disease and death.

One of the major challenges in curing hepatitis B is the unique biology of the virus. HBV replicates through covalently closed circular DNA (cccDNA) intermediates that integrate into the host genome. This makes complete eradication of the virus difficult, even with effective antiviral treatments. Another challenge is the impaired immune response to HBV in chronically infected individuals. The virus has evolved multiple mechanisms to evade the immune system, making it difficult for the body to clear the infection.

Currently available antiviral drugs, nucleos

A promising new treatment approach is the use of immune-based therapies. These therapies are designed to enhance the host’s immune response to the hepatitis B virus and help the body clear the virus. Several immune-based therapies are currently in clinical development, including vaccines, adoptive T-cell therapy, and gene therapy.

Another promising approach is to develop treatment combinations. These combinations combine different therapies, such as antiviral drugs and immunotherapy, to achieve a cure for hepatitis B. Several treatment combinations are currently in clinical development with the potential to cure HBV.

In addition to the biological challenges of curing hepatitis B, there are many clinical challenges. One challenge is the lack of clear endpoints for cure. Currently, functional cure is defined as sustained loss of HBsAg (the surface antigen of HBV) for at least 6 months after treatment. However, this does not guarantee that the virus has been completely eradicated from the body, as cccDNA may still be present. Therefore, restoration of HBV-specific immune responses is critical to control residual infection. The discovery and validation of novel biomarkers that predict functional cure will be important for monitoring new therapies and personalizing treatments.

Despite the challenges, significant progress is being made in developing new hepatitis B treatment strategies. New understanding of hepatitis B biology and antiviral immune responses has led to the identification of new drug targets and renewed interest in developing therapeutic combinations. Ongoing clinical trials are evaluating the safety and efficacy of these new approaches and will pave the way for a functional cure for HBV infection.

See article:

Roca Suarez AA, Zoulim F. Opportunities and challenges in curing hepatitis B. eGastroenterology 2023;1:e100021. doi:10.1136/egastro-2023-100021

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