Shah PA, et al. - Researchers conducted a long-term observational study in a cohort of patients with HBeAg (+) and (-) chronic hepatitis B (CHB) who achieved spontaneous HBsAg clearance CHB for assessing the patterns of HBsAg reduction in these patients. From an antiviral treatment-naive Alaska Native population who achieved HBsAg seroclearance from 1973 to 2009 with samples at least 2 years prior to HBsAg loss, they selected 17 HBeAg (+) and 48 HBeAg (-) patients with predominantly HBV genotypes D and F. The analysis revealed a significantly slower rate of HBsAg clearance among the HBeAg (+) patients. HBeAg (-) patients exhibited more uniform loss of HBsAg loss at a rate of about 4% over 25 years. The HBeAg (+) patients exhibited a similar average decline in HBeAg (1.8 log IU/ml/year) and HBsAg (1.5 log IU/ml /year) from baseline to HBeAg loss. They observed a significantly faster rate of HBsAg reduction before (1.5 log IU/ml/year) compared with after (0.4 log IU/ml /year) HBeAg clearance. A similar kinetic of HBsAg decline was noted after HBeAg loss to that noted among the HBeAg (-) patients (0.3 log IU/ml /year). A biphasic decline in HBsAg titers prior to and after HBeAg seroclearance is identified as a novel finding. Findings suggest that valuable information on the natural course of CHB could be gained via HBsAg quantification over time. Its kinetic may assist in predicting HBsAg loss particularly in the HBeAg (-) phase of CHB.