Hepatitis B Virus Cure: Targets and Future Therapies.

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Chronic hepatitis B virus (HBV) infection poses a significant global health burden, leading to liver fibrosis, cirrhosis, and hepatocellular carcinoma.
• Current antiviral therapies, primarily nucleos(t)ide analogues, effectively suppress HBV replication but rarely achieve hepatitis B surface antigen (HBsAg) loss or seroconversion due to incomplete targeting of the viral covalently closed circular DNA (cccDNA).

Purpose of the Study:

• To review newly investigated therapeutic compounds and emerging treatment strategies for chronic hepatitis B.
• To evaluate the potential of novel agents and combination therapies to achieve a functional cure for HBV infection, defined by HBsAg loss and seroconversion.

Main Methods:

• Review of preclinical and clinical trial data for novel anti-HBV agents.
• Analysis of therapeutic strategies targeting different stages of the HBV life cycle, including those acting on cccDNA.

Main Results:

• Current antiviral treatments achieve viral suppression but have limited success in achieving HBsAg loss (<10% in 5 years).
• Emerging therapies and combination regimens show promise in interrupting the HBV life cycle and increasing the rate of HBsAg seroclearance.

Conclusions:

• Achieving a functional cure for chronic hepatitis B requires strategies that eliminate the viral cccDNA reservoir.
• Optimized treatment regimens combining existing and novel anti-HBV agents are crucial for increasing the rates of HBsAg loss and achieving a cure.