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[HBsAg seroclearance: prognostic value for the response to treatment and the long-term outcome]
1Service d'Hépatologie et INSERM U773-CRB3, Hôpital Beaujon, Clichy, France. rami.moucari@inserm.fr
Insights
Hepatitis B surface antigen (HBsAg) clearance signifies a near-cure for chronic hepatitis B, improving survival and reducing liver disease complications. Interferon treatments significantly boost HBsAg seroclearance rates.
Area of Science:
- Hepatology
- Virology
- Immunology
Context:
- Chronic hepatitis B (CHB) is a leading global cause of liver cirrhosis and hepatocellular carcinoma.
- Hepatitis B surface antigen (HBsAg) is a key diagnostic marker for hepatitis B virus (HBV) infection.
Purpose:
- To explore the significance of HBsAg clearance as a functional cure for CHB.
- To evaluate the impact of different treatments on HBsAg seroclearance rates.
- To assess the role of serum HBsAg quantification in monitoring treatment response.
Summary:
- HBsAg clearance is associated with improved survival, reduced liver decompensation, and regression of fibrosis in CHB patients.
- Spontaneous HBsAg seroclearance occurs at 1-2% annually, often after a period of inactive disease.
- Interferon-based therapies, particularly pegylated interferon, significantly enhance HBsAg seroclearance rates (3-6 fold increase vs. untreated; 10-15% yearly with sustained response).
- Nucleos(t)ide analogues show limited impact on HBsAg seroclearance, especially in HBeAg-negative patients.
- Serum HBsAg levels correlate with intrahepatic cccDNA and can serve as a surrogate marker for monitoring treatment efficacy in HBeAg-negative patients receiving pegylated interferon.
Impact:
- HBsAg seroclearance represents a functional cure, significantly improving long-term outcomes for chronic hepatitis B patients.
- Understanding HBsAg dynamics guides treatment strategies and monitoring for CHB.
- Serum HBsAg quantification offers a non-invasive method for assessing treatment response and guiding therapy adjustments.
Abstract:
Chronic hepatitis B is a major cause of liver disease worldwide, ranking as the first cause of cirrhosis and hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) is usually used as a qualitative marker for the diagnosis of hepatitis B virus (HBV) infection. HBsAg clearance is the closest to cure outcome as one can expect to achieve in hepatitis B. Support for this comes from natural history studies demonstrating increased length of survival, lower rates of hepatic decompensation, reduction in the frequency of hepatocellular carcinoma, and regression of liver fibrosis in patients who clear HBsAg. HBsAg seroclearance may occur spontaneously at a yearly incidence of 1-2%, preceded usually by a long period of inactive disease. Interferon treatment enhanced HBsAg seroclearance by approximately three-fold in western studies and sixfold in Asian studies compared with non-treated patients. Pegylated interferon induced a 10-15% yearly rate of HBsAg seroclearance in patients who developed sustained virological response in clinical trials. By contrast, treatment with nucleos (t) ides analogues did not significantly affect the rate of HBsAg seroclearance, especially in patients with hepatitis B e antigen (HBeAg) - negative disease. Recently, serum HBsAg has been shown to be a surrogate marker of covalently closed circular DNA (cccDNA) concentration in the liver. Quantification of serum HBsAg has also been recently shown to be a promising tool for monitoring virologic response in HBeAg-negative patients treated with pegylated interferon.
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