Clinical Information

Hepatitis B surface antigen (HBsAg) is the first serologic marker appearing in the serum or plasma at 6 to 16 weeks following exposure to hepatitis B virus (HBV). In acute infection, HBsAg usually disappears in 1 to 2 months after the onset of symptoms. Persistence of HBsAg for more than 6 months in duration indicates development of either a chronic carrier state or chronic HBV infection.

Production of HBsAg is modulated by the interplay between the virus and host immune response, and the HBsAg level in serum inversely correlates with the immune control of HBV: the higher the immune control, the lower the HbsAg level in the infected individual. Quantitative HbsAg levels in serum or plasma reflect the amount and transcriptional activity of covalently closed circular DNA (cccDNA) inside the hepatocytes of individuals with chronic hepatitis B (CHB). Therefore, quantitative HBsAg provides information concerning disease activity over and above an estimation of viral replication. In general, together with HBV DNA in serum or plasma, quantification of HBsAg in the same specimen is useful in the diagnosis of the true inactive HBV carrier state and in monitoring the clinical response to pegylated-interferon (PegIFN) and/or nucleoside/nucleotide analog (NA) therapy for CHB.

The inactive HBV carrier state is often defined by persistently normal alanine aminotransferase levels and low HBV DNA levels in serum or plasma (<2000 IU/mL) in an individual negative for hepatitis B e antigen (HBeAg) with no or minimal liver injury. These individuals can have very good prognosis without the need of antiviral therapy, despite having fluctuating levels of HBV DNA over time. Some patients have low HBV DNA levels at one time but viral and biochemical reactivation later. The HBsAg levels in serum or plasma of inactive HBV carriers tend to change very slowly with time and remain at low levels (ie, <1000 IU/mL), serving as a useful adjunct to HBV DNA level to aid in the identification of these individuals.

Clinical studies have shown that the change of HBsAg level in serum or plasma during PegIFN therapy mimics the change of both intrahepatic cccDNA and intrahepatic HBsAg, suggesting that a decline of HBsAg level in serum or plasma is associated with the induction of an effective anti-HBV immune response for monitoring CHB patients treated with PegIFN. Since decline of HBsAg level in serum or plasma during PegIFN therapy is confined mainly to patients who achieve therapeutic response, monitoring of HBsAg levels help distinguish patients likely to achieve a response from those who will not. On treatment, HBsAg levels at weeks 12 and 24 of PegIFN therapy have high negative predictive values for therapeutic response and are useful to serve as stopping rules for the non-responders.

Although HBV DNA remains the key molecular marker to monitor the response and adherence of NA treatment in CHB patients, monitoring of the HBsAg level every 6 months can give an estimate on the duration of NA treatment needed to achieve HBsAg seroclearance. HBsAg levels may be useful to predict HBV reactivation or sustained response after cessation of NA therapy. Currently, HBsAg seroclearance is still the acceptable endpoint to stop NA in patients who are HBeAg negative.