Serologic and virologic kinetics after stopping nucleoside analogue therapy in hepatitis B surface antigen (HBSAG) seroclearance

Abstract

BACKGROUND: Hepatitis B surface antigen (HBsAg) seroclearance after nucleoside analogue (NA) therapy is an uncommon event. The serologic and virologic kinetics after HBsAg seroclearance and cessation of therapy have not been previously described. METHODS: Between December 1999 and June 2011, 42 (73.9% male) patients developed HBsAg seroclearance after NA therapy. Serum HBV DNA and HBsAg levels were determined at baseline, time of HBsAg loss and after cessation of therapy. They were measured by Cobas Taqman assay (lower limit of detection 20 IU/mL) and Roche Elecsys HBsAg II assay (lower limit of detection 0.05 IU/mL) respectively. RESULTS: HBsAg seroclearance occurred in a median duration of 48.8 (range: 4.8 to 189.0) months after therapy commencement. Twenty-nine (69.0%), 10 (23.8%), 2 (4.8%) and 1 (2.4%) patients were on lamivudine, entecavir, lamivudine plus adefovir and telbivudine respectively. At the time of writing, 22 patients (52.4%) developed anti-HBs. Seven patients (16.7%, 6 on lamivudine, 1 on entecavir) stopped therapy after a median treatment duration of 39.9 (range 12.8 to 112.4) months, before HBsAg seroclearance which occurred after at a median time of 36.4 (range 17.2 to 94.9) months. Of the 35 patients who continued taking NA till HBsAg seroclearance, 17 (48.6%) stopped therapy 17.9 (range 1.4 to 87.6) months after HBsAg seroclearance. Among patients with therapy ceased for more than 6 months (n = 14, median time 21.9 months, range 6.4 to 53.3 months), 13 (92.6%) maintained an undetectable level of serum HBV DNA and HBsAg. One patient (7.1%) developed HBsAg seroreversion and hepatitic flare 29 months after cessation of lamivudine. She achieved HBsAg seroclearance and viral suppression to undetectable levels again at 4 and 7 months respectively after retreatment of entecavir. There were no cases of HBsAg seroreversion among the 18 patients (51.4%) maintaining therapy 15.9 (range 3.7 to 58.8) months after HBsAg seroclearance. CONCLUSION: Majority of CHB patients who stopped treatment after CHB seroclearance maintained virologic and serologic stability.