Differential roles of serum hepatitis B virus DNA and hepatitis B surface antigen level in predicting virological breakthrough in patients receiving lamivudine therapy

Background and Aim The role of serum hepatitis B surface antigen ( HB s A g) level in determining virological breakthrough ( VB ) for patients with hepatitis B virus ( HBV ) infection receiving lamivudine remains unclear. The study aimed to evaluate the impact of serum HB s A g levels on VB among patients receiving lamivudine therapy, especially in a setting of low HBV viral load. Methods Two hundred sixty‐eight consecutive treatment‐naïve patients who underwent lamivudine therapy for chronic hepatitis B were enrolled. Factors in terms of VB were analyzed by multivariate analysis. Results After a median treatment duration of 67.1 weeks, 102 patients had VB . Multivariate analysis showed that positive hepatitis B e antigen ( HB e A g) (hazard ratio 2.165, P  = 0.026) and HBV DNA levels ≥ 2000 IU /m L after 6 months of lamivudine therapy (hazard ratio 5.236, P  = 0.001) were independent risk factors predicting VB . The cumulative VB rates stratified by HB e A g‐positive and ‐negative at 3 years were 44.7% and 26.3%, respectively. At 3 years, the cumulative VB rates stratified by the HBV DNA < 2000 and ≥ 2000  IU /m L after 6 months of therapy were 25.5% and 79.4%, respectively. For HB e A g‐positive patients with serum HBV DNA < 2000  IU /m L after 6 months of therapy, baseline HB s A g levels ≥ 20 000  IU /m L was the only risk factor associated with VB . Conclusions For chronic hepatitis B patients treated with lamivudine, serum HBV DNA level > 2000  IU /m L after 6 months of therapy could predict subsequent VB . In patients with lower on‐treatment viral load, baseline serum HB s A g level is associated with the emergence of VB , especially for those with serum positive HB e A g.