Chronic hepatitis B: New potential therapeutic drugs target

Abstract

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.

The progress of molecules and strategies for the treatment of HBV infection

“…In addition, they also compete with natural nucleotide substrates to interrupt HBV DNA synthesis. There are some NAs that have been approved for CHB treatment, including lamivudine, adefovir dipivoxil, entecavir, telbivudine, and tenofovir ( Leowattana and Leowattana, 2022 ). Long-term treatment with NAs could reduce numbers of cccDNA pools in HBV-infected hepatocytes by inhibiting nucleocapsid recycling ( Leowattana and Leowattana, 2022 ).…”

Cautious optimism in anticipation of hepatitis B curative therapies

“…We read with great pleasure the article by Leowattana et al [ 1 ] about new emerging therapies in treatment of chronic hepatitis B. They presented a comprehensive review of currently available therapies, pathophysiology of the hepatitis B infection, and developing new therapies.…”

“…As a result, new therapies are now being investigated that are aimed at a complete cure and loss of hepatitis B surface antigen (HBsAg). Leowattana et al [ 1 ] presented a comprehensive discussion of developing new therapies, which include agents that inhibit entry of hepatitis B virus (HBV) into hepatocytes, interfere with cccDNA or HBV transcription, alternate nucleocapsid assembly, and prevent HBsAg release from the hepatocytes. The authors are hopeful that given currently available evidence on these emerging therapies, chronic hepatitis B could become a curable disease in the near future.…”

“…Nucleocapsid assembly modulators are another exciting modality reported by Leowattana et al [ 1 ] but it is another therapy that should be treated with caution until more data from larger clinical trials is available. Zhang et al [ 6 ] reported that 75% of patients in their study evaluating nucleocapsid assembly modulators experienced elevations in aminotransferases with 4 out of 24 patients requiring to stop therapy and receive glutathione.…”

“…We commend Leowattana et al [ 1 ] for their comprehensive review of the emerging new therapies that have the potential to cure chronic hepatitis B. Our goal was to merely add caution to the optimism and hopefully prompt larger clinical trial specific to hepatitis B population, so that more patients can safely benefit from the new therapies in the near future.…”