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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
Current trends and advances in antiviral therapy for chronic hepatitis B
Juan Li1,2, Siyi Liu1, Qijuan Zang1
1Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Insights
New antiviral drugs and immunotherapies show promise for a functional cure of chronic hepatitis B virus (HBV) infection. Combination therapy may offer a future treatment strategy for this global health concern.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Chronic hepatitis B virus (HBV) infection is a significant global health issue.
- Current treatments suppress HBV replication but do not eliminate the virus due to persistent cccDNA, viral DNA integration, and immune dysfunction.
- A functional cure for chronic HBV remains a major therapeutic challenge.
Purpose of the Study:
- To review recent advancements in the treatment of chronic hepatitis B.
- To discuss the limitations of current therapies and explore novel approaches for achieving a functional cure.
- To provide perspectives on future therapeutic strategies for chronic HBV.
Main Methods:
- Review of current literature on HBV antiviral drugs and immunomodulatory agents.
- Analysis of direct-acting antiviral agents in clinical trials, including entry inhibitors, capsid assembly modulators, and RNA interference.
- Examination of immunomodulatory agents such as TLR agonists, therapeutic vaccines, and checkpoint inhibitors.
Main Results:
- Significant progress has been made in developing novel direct-acting antiviral agents and immunotherapies.
- New drug candidates targeting various stages of the HBV lifecycle are advancing through clinical trials.
- Immunomodulatory agents are also emerging as potential therapeutic options.
Conclusions:
- Achieving a functional cure for chronic HBV requires novel therapeutic strategies beyond current suppressive treatments.
- Emerging direct-acting antivirals and immunotherapies offer new hope for a cure.
- Combination therapy is likely to be a key strategy in future chronic hepatitis B treatment.
Abstract:
Chronic hepatitis B virus (HBV) infection is a global public health concern. Existing antiviral drugs, including nucleos(t)ide analogs and interferon-α, can suppress HBV replication and improve the prognosis. However, the persistence of covalently closed circular DNA (cccDNA), the integration of HBV-DNA into the host genome, and compromised immune responses impede the successful treatment of hepatitis B. While achieving a functional cure of HBV remains elusive with the current treatment methods, this is the goal of new therapeutic approaches. Therefore, developing novel antiviral drugs is necessary for achieving a functional or complete cure for chronic hepatitis B. In recent years, substantial progress has been made in drug discovery and development for HBV infection. Direct-acting antiviral agents such as entry inhibitors, capsid assembly modulators, subviral particle release inhibitors, cccDNA silencers, and RNA interference molecules have entered clinical trials. In addition, several immunomodulatory agents, including toll-like receptor agonists, therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also making their way toward clinical use. In this review, we summarize the recent progress and limitations of chronic hepatitis B treatment and discuss perspectives on approaches to achieving functional cure. Although it will take some time for these new antiviral drugs to be widely used in clinical practice, combination therapy may become a preferable treatment option in the future.
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