Decreasing Levels of HBsAg Predict HBsAg Seroclearance in Patients With Inactive Chronic Hepatitis B Virus Infection

Background & Aims: Serum levels of hepatitis B surface antigen (HBsAg) decrease gradually during chronic hepatitis B virus infection. We investigated the association between levels of HBsAg and HBsAg seroclearance. Methods: We studied data from 46 patients who underwent spontaneous seroclearance of HBsAg (median age at seroclearance, 48 y; 87% male; 76% infected with genotype B). There were 46 controls matched for age, sex, and hepatitis B virus genotype, and e antigen status with persistently normal levels of alanine aminotransferase and seropositive for HBsAg. Levels of HBsAg were assessed in serum specimens collected 5 years 3 years, and 1 year before HBsAg seroclearance (or before the last examination, for controls). Results: The decrease in HBsAg level was significant and accelerated within the 3 years before HBsAg seroclearance; there was no significant decrease in serum level of HBsAg among controls (P < .0001). The positive predictive value (PPV) for HBsAg seroclearance within 1 year was 36% among patients with HBsAg levels of 200 IU/mL, increasing to 44%, 54%, and 67% among patients with HBsAg levels of 100 IU/mL, 50 IU/mL, or 10 IU/mL, respectively; the negative predictive value (NPV) for these levels was 96% or greater. The combination of HBsAg level less than 200 IU/mL and a decrease of 1 or more log ₁₀ IU/mL in a preceding 2-year period had PPVs of 97% and 100% for HBsAg seroclearance at 1 and 3 years, respectively; the NPVs were 100% and 92%, respectively. Conclusions: The decrease in the level of HBsAg accelerates during the 3 years before HBsAg seroclearance. Levels of HBsAg of 200 IU/mL or less have high NPVs for HBsAg seroclearance; PPVs increase to 97% to 100% when combined with a 1 log IU/mL or more decrease in level of HBsAg over a 2-year period.