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World J Virol. Jan 25, 2022; 11(1): 57-72
Published online Jan 25, 2022. doi: 10.5501/wjv.v11.i1.57
Chronic hepatitis B: New potential therapeutic drugs target
Wattana Leowattana, Tawithep Leowattana
Wattana Leowattana, Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
Tawithep Leowattana, Department of Medicine, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand
Author contributions: Leowattana W wrote the paper; Leowattana T collected the data.
Conflict-of-interest statement: The authors declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Wattana Leowattana, MD, MSc, PhD, Professor, Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, No. 420/6 rajavithi road, rachatawee, Bangkok 10400, Thailand.
Received: May 31, 2021
Peer-review started: May 31, 2021
First decision: July 31, 2021
Revised: August 13, 2021
Accepted: January 5, 2022
Article in press: January 5, 2022
Published online: January 25, 2022

Chronic hepatitis B (CHB) infection remains the most causative agent of liver-related morbidity and mortality worldwide. It impacts nearly 300 million people. The current treatment for chronic infection with the hepatitis B virus (HBV) is complex and lacks a durable treatment response, especially hepatitis B surface antigen (HBsAg) loss, necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA (cccDNA). New drugs that target distinct steps of the HBV life cycle have been investigated, which comprise inhibiting the entry of HBV into hepatocytes, disrupting or silencing HBV cccDNA, modulating nucleocapsid assembly, interfering HBV transcription, and inhibiting HBsAg release. The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication. This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs. Hopefully, with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle, the ultimate eradication of CHB infection will soon be achieved.

Keywords: Chronic hepatitis B, Hepatitis B surface antigen, Hepatitis B surface antibody, Covalently closed circular DNA, Direct acting antiviral drugs, Functional cure, Entry block, Nucleocapsid assembly modulator, Interfering hepatitis B virus transcription, Inhibiting hepatitis B surface antigen release

Core Tip: Current treatment of chronic hepatitis B infection with nucleos(t)ide analogs causes long-term suppression of hepatitis B virus (HBV) DNA levels, significantly improving hepatocellular injury and extrahepatic complications. However, the risk of hepatocellular carcinoma remains increased. New direct antiviral drugs that target the HBV life cycle, including entry blockers, assembly modulators, covalently closed circular DNA (cccDNA) disruptors, and hepatitis B surface antigen release inhibitors, would lead to hepatitis B surface antigen loss and a functional cure. Moreover, a combination of antiviral drugs with an immune-modulator could enhance the elimination of cccDNA and provide a definitive cure.