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Published on: September 25, 2019
Current and novel modalities for management of chronic hepatitis B infection
Iman Ibrahim Salama1, Samia M Sami2, Somaia I Salama3
1Department of Community Medicine Research, National Research Centre, Giza 12411, Dokki, Egypt. salamaiman@yahoo.com.
Insights
Chronic hepatitis B (CHB) affects millions globally, with current treatments offering limited functional cure rates. Novel antiviral and immunotherapies show promise for effective CHB control and potential cure.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Chronic hepatitis B viral infection (CHB) impacts over 296 million people worldwide, presenting significant elimination challenges.
- CHB pathogenesis involves HBV-specific immune tolerance, intrahepatic covalently closed circular DNA, and integrated HBV.
- Serum hepatitis B core-related antigen serves as a key surrogate marker for intrahepatic covalently closed circular DNA.
Purpose of the Study:
- To review current challenges in CHB treatment and explore novel therapeutic strategies.
- To discuss the potential of direct-acting antivirals and immunomodulatory therapies for achieving functional cure.
- To highlight the importance of new diagnostic assays for evaluating novel CHB therapies.
Main Methods:
- Review of existing literature on CHB pathogenesis and treatment.
- Analysis of novel antiviral and immunotherapeutic approaches, including direct-acting antivirals and immune modulators.
- Discussion of emerging strategies like checkpoint inhibitors, therapeutic vaccines, and engineered T cells.
Main Results:
- Current therapies (nucleos(t)ide analogues, interferon) achieve functional cure in less than 10% of CHB patients.
- Novel therapies aim to reduce viral antigen load, enhance innate and adaptive immunity, and overcome immune tolerance.
- Combined therapeutic approaches hold potential for successful HBV control and cure.
Conclusions:
- Functional cure of CHB, defined by durable HBsAg loss, remains a significant unmet need.
- Emerging antiviral and immunotherapies offer promising avenues for improved CHB management.
- Careful safety evaluation and development of new diagnostic tools are crucial for advancing CHB curative therapies.
Abstract:
Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV "cure" is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.
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