Hepatitis B surface antigen kinetics during 10 years of virologic suppression with nucleoside analogue therapy

Abstract

BACKGROUND: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleoside analogue therapy has not been described. METHODS: We recruited 71 patients achieving persistent viro-logic suppression (Serum HBV DNA < 2,000 IU/mL) during lamivudine therapy for at least 10 years (10 patients for 15 years). Serum HBsAg (Elecsys HBsAg II) and HBV DNA levels (Cobas Taqman) were determined at baseline, year 5 and year 10. HBV genotype was determined by a line probe assay. RESULTS: The median age at lamivudine commencement was 38.6 (range 13.1 to 66.7) years. 57 patients (78.1%) were male and 43 (58.9%) were hepatitis B e antigen (HBeAg)-positive, with all 43 patients achieving HBeAg seroconversion after a median period of 2.82 (range 0.13 to 10.85) months. There was no significant difference in the median annual HBsAg decline rate from baseline to year 5 and from year 5 to 10 (0.350 and 0.359 log IU/mL/year respectively, p = 0.749). There was no difference in median annual HBsAg decline when comparing baseline HBeAg-positive and negative patients (0.111 and 0.064 log IU/ mL/year respectively, p = 0.165), genotypes B and C (0.081 and 0.125 log IU/mL/year respectively, p = 0.170), and persistent undetectable viremia versus intermediate levels of viremia of 20–2000 IU/mL (0.081 and 0.124 log IU/mL/year respectively, p = 0.232).7 patients (9.6% 4 HBeAg-positive and 3 HBeAg-negative) achieved HBsAg seroclearance after a median period of 7.59 (range 3.59 to 12.15) years. The 7 patients achieving HBsAg seroclearance, when compared to the remaining 64 patients, had a lower median baseline HBsAg level (2.72 and 3.67 log IU/mL respectively, p = 0.029) and a significantly larger HBsAg decline (0.401 log IU/mL/year versus 0.081 log IU/mL respectively, p < 0.001) CONCLUSION: HBsAg reduction remained relatively stable during long-term lamivudine therapy. A low baseline HBsAg level and an increased HBsAg decline rate would be a pre-requisite for subsequent HBsAg seroclearance.