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Patterns of HBeAg and HBsAg clearance among a treatment‐naive Alaskan Cohort in a long‐term observational study

In this long-term observational study, we examined the patterns of HBsAg reduction in a cohort of patients with HBeAg (+) and (-) chronic hepatitis B (CHB) who achieved spontaneous HBsAg clearance CHB Patients were selected 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. ADVIA Centaur HBsAg and HBeAg quantitative assays (Siemens Healthcare Diagnostics, USA) were utilized. 17 HBeAg (+) and 48 HBeAg (-) patients with predominantly HBV genotypes D and F were enrolled. The average follow-up was 19.5 years and 16.4 years respectively. Rate of HBsAg clearance was significantly slower among the HBeAg (+) patients (p=0.001). HBsAg loss was more uniform at a rate of about 4% over 25 years for HBeAg (-) patients. Among the HBeAg (+) patients, the average decline in HBeAg (1.8 log IU/ml/year) and HBsAg (1.5 log IU/ml /year) from baseline to HBeAg loss were similar (p=0.2). The rate of HBsAg reduction was significantly faster before (1.5 log IU/ml/year) compared to after (0.4 log IU/ml /year) HBeAg clearance (p=0.004). The kinetic of HBsAg decline after HBeAg loss was similar to that among the HBeAg (-) patients (0.3 log IU/ml /year). The observation of a biphasic decline in HBsAg titers prior to and after HBeAg seroclearance is novel. HBsAg quantification over time provides valuable information on the natural course of CHB. Its kinetic can predict HBsAg loss especially in the HBeAg (-) phase of CHB.