We read with interest the articles by Brunetto et al.1 and Moucari et al.2 concerning the role of hepatitis B surface antigen (HBsAg) kinetics for long-term outcome of interferon-based antiviral therapy in chronic hepatitis B infection. Whereas the study by Moucari et al. focuses on HBsAg decline, the study by Brunetto et al. focuses on HBsAg levels at week 48.
In the setting of nucleos(t)ide-based antiviral therapy, we have earlier observed a “2-log rule” for HBsAg clearance, in which patients with both a 2-log drop of HBsAg plus achieving an HBsAg level of less than 2-log (or 100 IU/mL) showed eventual HBsAg clearance unless they developed viral resistance, whereas the prediction of either factor alone was less specific.3 The role of HBsAg decline was also recently confirmed for telbivudine, although the authors likewise did not address the dual aspect of HBsAg decline and HBsAg drop below a threshold.4 The role of combining both the decline and threshold was recently also promoted in hepatitis C virus therapy, where a recent study confirmed the increase in early predictability of achieving sustained viral response by combining the decline and threshold approach.5
Thus, we were wondering whether the combination of, for example, a 1-log or 2-log HBsAg decline and reduction below 1-log or 2-log (or 100 IU/mL) HBsAg would also be highly predictive for eventual HBsAg clearance for interferon-based therapies in chronic hepatitis B infection.