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 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.