Hepatitis B virus X protein-targeted therapeutic strategies toward a functional cure for chronic hepatitis B infection: A review

Abstract

Background: Chronic hepatitis B (CHB) remains a major global health challenge, with persistent covalently closed circular DNA (cccDNA) and viral integration leading to lifelong infection, cirrhosis, and hepatocellular carcinoma (HCC). Current antiviral therapies suppress replication but rarely achieve a functional cure. The multifunctional hepatitis B virus (HBV) X (HBx) protein is well known to sustain viral replication, impair host immune responses, and promote hepatocarcinogenesis, which makes it an attractive therapeutic target. Aim: This review synthesizes current literature supporting HBx as a promising therapeutic target to achieve a functional cure of CHB. Conclusion: HBx is a high-value therapeutic target with potential to accelerate progress toward a functional cure. Destabilization or downregulation of HBx would not only attenuate its oncogenic signaling but also limit relapse after treatment discontinuation and diminish the cccDNA reservoir and viral antigen load. Relevance for patients: Multitargeted treatment regimens incorporating HBx-directed therapies hold the potential to achieve durable viral suppression and a functional cure, and to reduce the risk of HCC. The combined strategies could transform the long-term management and outcomes for patients with CHB.

Keywords

Hepatitis B virus / Hepatitis B virus X protein / Chronic hepatitis B / Covalently closed circular DNA / Viral persistence / Furanocoumarins / Functional cure

Acknowledgments

None.

Funding

This work was supported in part by a J.C. Bose National Fellowship (Grant no. SR/S2/JCB-80/2012) from the Department of Science and Technology, Government of India, New Delhi (awarded to V.K.). S.G. received a senior research fellowship from the University Grants Commission, India (grant no. 590/CSIR-UGC NET June 2017).

Conflict of interest

The authors declare that they have no competing interests.

Author contributions

Conceptualization: Vijay Kumar Visualization: Sunita Giri Writing – original draft: Sunita Giri Writing – review & editing: Vijay Kumar

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Not applicable.

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