Future treatments for hepatitis delta virus infection

Area of Science:

• Virology
• Hepatology
• Drug Development

Background:

• Hepatitis delta virus (HDV) is a defective RNA virus that requires hepatitis B virus surface antigen (HBsAg) for its life cycle and infects hepatocytes via the NTCP receptor.
• HDV infection poses significant risks for severe liver disease, including end-stage liver disease and hepatocellular carcinoma.
• Current treatment options for HDV are limited to pegylated-interferon (PEG-IFN) for 48 weeks, with no alternatives for non-responders.

Purpose of the Study:

• To review new insights into the HDV life cycle.
• To discuss novel antiviral drug classes in development for HDV infection.
• To explore emerging therapeutic strategies targeting viral entry, prenylation, and HBsAg release.

Main Methods:

• Review of current scientific literature on HDV pathogenesis and drug development.
• Analysis of the HDV life cycle, including viral entry, replication, and assembly.
• Examination of antiviral agents in Phase II and III clinical trials.

Main Results:

• Understanding the HDV life cycle has revealed new targets for therapeutic intervention.
• Novel drug candidates, including bulevirtide (entry inhibitor), lonafarnib (prenylation inhibitor), and REP 2139 (HBsAg release inhibitor), are in advanced stages of development.
• These agents aim to achieve HBsAg clearance or sustained HDV virological response.

Conclusions:

• New therapeutic strategies are emerging to address the unmet medical needs in HDV treatment.
• Targeting specific steps in the HDV life cycle, such as viral entry and assembly, shows promise.
• Further development of these novel drugs is crucial for improving outcomes in patients with chronic HDV infection.