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A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
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What will it take to cure hepatitis B?
Wen-Juei Jeng1,2, Anna S F Lok3
1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan.
Hepatology Communications
|March 27, 2023
Summary
Achieving a cure for chronic hepatitis B virus (HBV) infection requires eliminating all forms of HBV DNA, not just suppressing replication. New therapies aim to achieve sustained HBsAg loss for a functional cure.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Current treatments for chronic hepatitis B virus (HBV) infection, including pegylated interferon-alfa (pegIFNα) and nucleos(t)ide analogs (NAs), effectively suppress viral replication and reduce disease progression but often lead to relapse without hepatitis B surface antigen (HBsAg) loss.
- A functional cure for HBV, defined as sustained HBsAg loss after finite therapy, necessitates complete suppression of viral replication and protein production, alongside restoration of the immune response to HBV.
Purpose of the Study:
- To review the current landscape and future directions for achieving a functional cure for chronic HBV infection.
- To highlight the challenges in eliminating HBsAg, including its origins from both cccDNA and integrated HBV DNA.
- To emphasize the need for novel therapeutic strategies and improved diagnostic assays for assessing treatment response.
Main Methods:
- Review of existing and emerging therapeutic strategies for chronic HBV, including direct-acting antivirals and immunomodulatory therapies.
- Analysis of the limitations of current treatments in achieving sustained HBsAg loss.
- Discussion of the role of covalently closed circular DNA (cccDNA) and integrated HBV DNA in viral persistence.
- Exploration of the necessity for advanced diagnostic tools to monitor HBV RNA, hepatitis B core-related antigen, and immune recovery.
Main Results:
- HBsAg loss remains rare even with combination therapies due to the persistence of viral DNA in both cccDNA and integrated forms.
- Direct-acting antivirals targeting various stages of the HBV life cycle are under clinical investigation.
- Immunomodulatory approaches are being developed to restore anti-HBV immunity.
- Development of new assays is crucial for differentiating HBsAg sources and assessing immune recovery.
Conclusions:
- Achieving a functional cure for HBV requires therapies that can eliminate or silence both cccDNA and integrated HBV DNA.
- Improved diagnostic assays are essential for accurate treatment monitoring and personalized therapeutic strategies.
- Platform trials are proposed to efficiently evaluate multiple combination therapies.
- Ensuring patient safety remains a priority, building upon the favorable safety profile of existing NA therapies.
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