Research Perspectives:

Hepatitis B x antigen (HBx) is an important therapeutic target in the pathogenesis of hepatocellular carcinoma

Arvin Medhat, Alla Arzumanyan and Mark A. Feitelson _

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Oncotarget. 2021; 12:2421-2433. https://doi.org/10.18632/oncotarget.28077

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Arvin Medhat1, Alla Arzumanyan2 and Mark A. Feitelson2

1 Department of Molecular Cell Biology, Azad University, North Unit, Tehran, Iran

2 Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA, USA

Correspondence to:

Mark A. Feitelson, email: [email protected]

Keywords: chronic liver disease; hepatocellular carcinoma; HBx; functional cure; epigenetic

Received: May 31, 2021     Accepted: September 04, 2021     Published: November 23, 2021

Copyright: © 2021 Medhat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Hepatitis B virus (HBV) is a human pathogen that has infected an estimated two billion people worldwide. Despite the availability of highly efficacious vaccines, universal screening of the blood supply for virus, and potent direct acting anti-viral drugs, there are more than 250 million carriers of HBV who are at risk for the sequential development of hepatitis, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). More than 800,000 deaths per year are attributed to chronic hepatitis B. Many different therapeutic approaches have been developed to block virus replication, and although effective, none are curative. These treatments have little or no impact upon the portions of integrated HBV DNA, which often encode the virus regulatory protein, HBx. Although given little attention, HBx is an important therapeutic target because it contributes importantly to (a) HBV replication, (b) in protecting infected cells from immune mediated destruction during chronic infection, and (c) in the development of HCC. Thus, the development of therapies targeting HBx, combined with other established therapies, will provide a functional cure that will target virus replication and further reduce or eliminate both the morbidity and mortality associated with chronic liver disease and HCC. Simultaneous targeting of all these characteristics underscores the importance of developing therapies against HBx.

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