To "be" or not to "be": that is the question

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Current hepatitis B treatment guidelines use hepatitis B early antigen (HBeAg) seroconversion as the primary endpoint for oral antiviral therapy in HBeAg-positive patients.
• This approach is challenged by high HBeAg relapse rates, frequent mixed viral infections, and the prevalence of HBeAg-negative hepatitis B disease.

Discussion:

• The utility of HBeAg status as a treatment endpoint or trigger for therapy initiation is diminishing.
• Hepatitis B surface antigen (HBsAg) loss or seroconversion, particularly when combined with undetectable HBV DNA, represents a more robust indicator of treatment success.

Key Insights:

• HBeAg seroconversion is an unreliable endpoint for hepatitis B treatment due to high relapse rates and disease variability.
• Hepatitis B surface antigen (HBsAg) loss is a superior marker for favorable prognosis in both HBeAg-positive and HBeAg-negative hepatitis B.
• Treatment cessation should be considered when both HBsAg loss/seroconversion and undetectable HBV DNA are achieved.

Outlook:

• Future hepatitis B treatment strategies should prioritize HBsAg loss as the definitive endpoint.
• Revised guidelines are necessary to incorporate HBsAg loss and undetectable HBV DNA for optimizing antiviral therapy cessation.
• Further research into the long-term implications of HBsAg loss and its correlation with sustained viral suppression is warranted.