This clinically relevant review focuses on recent findings relating to hepatitis B surface antigen (HBsAg) quantitation in untreated and treated patients with chronic hepatitis B. Recent studies and emerging data have shown that both HBsAg and hepatitis B virus (HBV) DNA levels decline along the natural course of chronic HBV infection, being lowest in inactive phase which is also characterized by the highest HBsAg/HBV DNA ratio. It was demonstrated that combined use of HBsAg and HBV DNA levels might help identify true inactive carriers with high accuracy.

Retrospective analyses of HBsAg levels in patients undergoing therapy suggest a role for HBsAg quantitation in monitoring response to therapy. Interferon-based therapy results in greater overall decline in serum HBsAg level than nucleos(t)ide analogs (NAs) . A rapid on-treatment decline in HBsAg level appears to be predictive of sustained response. With the aid of HBsAg quantitation, it appears that we could anticipate an individualized approach to tailoring treatment duration. Early stopping rules being proposed for patients not responding to pegylated interferon, based on lack of HBsAg decline, represent a step towards a response-guided approach.

The development of stopping rules for patients treated with NAs would be a desirable step to reduce the burden of a need for life-long therapy. However, before stopping rules for anti-viral therapy can be applied, there is still more to learn about the kinetics of HBsAg decline, in both natural history and response to therapy, to better define the best timing and relevant HBsAg cut-off levels and how best to apply these in clinical practice.