Long‐term entecavir therapy results in falls in serum hepatitis B surface antigen levels and seroclearance in nucleos(t)ide‐naïve chronic hepatitis B patients

Summary Entecavir ( ETV ) is reported to result in suppression of hepatitis B virus DNA ( HBV DNA ) replication with minimal drug resistance. However, information on the long‐term effect of such therapy on serum hepatitis B surface antigen ( HB s A g) level and elimination of HB s A g is not available. ETV therapy was started in 553 nucleos(t)ide‐naïve patients with chronic hepatitis B infection ( HB e A g positive: 45%) in our hospital. Serum HB s A g levels were measured serially by the Architect assay. The median baseline HB s A g was 2180 IU/mL (0.12–243 000 IU/mL), and median follow‐up period was 3.0 years, with 529, 475, 355, 247 and 163 patients followed‐up for 1, 2, 3, 4 and 5 years, respectively. At year 5, the mean log HB s A g decline from baseline was −0.48 log IU/mL, and the cumulative HB s A g clearance rate was 3.5%. Multivariate analysis identified HBV DNA level at baseline (<3.0 log copies IU/mL, odd ratio = 10.2; 95% confidence interval = 1.87–55.5, P  =   0.007) and HBsAg level (<500 IU/mL, odd ratio = 29.4; 95% confidence interval = 2.80–333, P  =   0.005) as independent predictors of HB s A g seroclearance. These results indicate that although serum HB s A g level declines gradually during ETV therapy, HB s A g seroclearance remains a rare event.