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Interferon-α for Immune Modulation in Chronic Hepatitis B Toward Functional Cure
Asha Ashuo1, Jia Liu2, Zhenghong Yuan1
1Key Laboratory of Medical Molecular Virology (MOE/NHC), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, 200032, China.
Insights
Interferon-alfa (IFN-α) helps fight chronic hepatitis B by regulating immune responses. Advances in IFN-α therapies offer new hope for a functional cure, despite current limitations.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Chronic hepatitis B (CHB) is a significant global health issue, characterized by persistent viral DNA and compromised immunity.
- Interferon-alfa (IFN-α), a crucial cytokine, inhibits hepatitis B virus (HBV) replication and modulates immune responses.
Purpose of the Study:
- To review current advancements in IFN-α-mediated immune regulation in CHB.
- To highlight the impact of IFN-α on various immune cells and its potential for viral clearance.
Main Methods:
- Literature review of studies on IFN-α's role in CHB.
- Analysis of immune cell responses to IFN-α.
- Evaluation of novel therapeutic strategies combining IFN-α.
Main Results:
- IFN-α reprograms immune responses, aiding viral clearance, but clinical efficacy is limited by response rates and side effects.
- Progress in cytokine engineering, subtype research, and combination therapies shows promise for improved outcomes.
Conclusions:
- Optimizing IFN-α-based interventions is crucial for enhancing CHB treatment.
- IFN-α is a key component for developing innovative therapies aiming for a functional cure of CHB.
Abstract:
Chronic hepatitis B (CHB) remains a major global health challenge, largely due to the persistence of covalently closed circular DNA (cccDNA) and impaired host immunity. Interferon-α (IFN-α), a key antiviral cytokine, not only directly restricts HBV replication but also orchestrates innate and adaptive immune responses. This review summarizes current advances in IFN-α-mediated immune regulation, highlighting its effects across diverse immune cell populations. Evidence indicates that IFN-α can reprogram immune responses to promote viral clearance, although clinical efficacy is limited by modest response rates and adverse effects. Recent progress in cytokine engineering, subtype research, and rational combination strategies-including nucleo(s/t)ide analogs, RNA interference therapeutics, antisense oligonucleotides, therapeutic vaccines, and beyond-has expanded opportunities to improve treatment outcomes. While challenges remain, these advances lay the foundation for optimizing IFN-α-based interventions and highlight IFN-α as a key driver for innovative therapies aimed at achieving a functional cure of chronic hepatitis B.
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