Serum hepatitis B surface antigen kinetics in severe reactivation of hepatitis B e antigen negative chronic hepatitis B patients receiving nucleoside/nucleotide analogues

Background: Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients. Methods: HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied. Those presented with severe reactivation (alanine aminotransferase [ALT] >= 5 times of normal) were compared to those with mild hepatitis. Serum HBsAg level was measured by Elecsys HBsAg II Quant assay (Roche) at baseline and 6-monthly. Results: A total of 192 (74 severe reactivation) patients were studied. Eighty-one (42%), 74 (39%) and 37 (19%) patients were on lamivudine, entecavir and telbivudine, respectively. Forty-four (23%) patients had early HBsAg decline, that is, >= 0.5 log(10) reduction, at month 6. Patients with severe reactivation had higher serum baseline ALT (1,415 +/- 897 versus 73 +/- 39 IU/l), HBV DNA (6.4 +/- 1.6 versus 5.2 +/- 1.2 log(10) IU/ml) and HBsAg (3.3 +/- 1.0 versus 2.9 +/- 0.6 log(10) IU/ml), as well as an earlier HBsAg decline (50% versus 6%; all P < 0.001) than those without. The HBsAg change of patients with severe reactivation was higher at months 0-6 (-0.58 +/- -1.26 versus -0.01 +/- -0.26 log(10) IU/ml; P < 0.001) but then became comparable from months 6-24 (-0.19 +/- -0.60 versus -0.13 +/- -0.19 log(10) IU/ml; P = 0.85), compared to those presented with mild hepatitis. Conclusions: Patients who presented with severe reactivation of HBeAg-negative hepatitis were more likely to develop early HBsAg decline during antiviral therapy. It may indicate a transient strong immune clearance with rapid initial reduction in serum HBsAg, which cannot be sustained due to a faster clearance of serum HBsAg.