Efficacy of entecavir therapy for hepatitis B e-antigen positive chronic hepatitis B patients with prior exposure to interferon or nucleoside/nucleotide analogues

Aim: The efficacy of entecavir (ETV) in treatment-experienced chronic hepatitis B (CHB) patients remains unclear. We evaluated the therapeutic responses and virological breakthrough following ETV treatment in hepatitis B e-antigen (HBeAg) positive CHB patients with prior exposure to interferon or nucleoside/nucleotide analog and treatment-naive patients. Methods: This was a retrospective, multicenter study of treatment (>1 year) with 0.5 mg ETV in 248 treatment-naive and 48 treatment-experienced HBeAg positive CHB patients (70.5% male; mean age, 40.5 years). The rates of undetectable hepatitis B virus (HBV) DNA, HBeAg loss and virological breakthrough were analyzed. Results: The median duration of ETV treatment was 27.3 months (range, 18.4-34.5). The rate of HBeAg loss was 41.9% (104/248) in treatment-naive and 45.8% (22/48) in treatment-experienced patients. The baseline serum HBV DNA and alanine aminotransferase levels were significant predictors for HBeAg loss (P = 0.01 and P = 0.04, respectively). There was no statistical difference between the groups in the rates of undetectable HBV DNA and HBeAg loss at any time point. Virological breakthrough occurred in 1.6% (4/248) of treatment-naive and 8.3% (4/48) of treatment-experienced patients. The four treatment-experienced patients with virological breakthrough had received prior lamivudine treatment. After excluding those treated with interferon, lamivudine-experienced patients had significantly greater virological breakthrough compared with treatment-naive patients (log-rank test, P = 0.034; univariate Cox regression, P = 0.047). Conclusion: ETV treatment efficacy, including virological response and HBeAg loss, was comparable between treatment-naive and treatment-experienced HBeAg positive CHB patients. Lamivudine-experienced patients had a higher risk of virological breakthrough than treatment-naive patients.