Objective: To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB).
Methods: In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles.
Results: At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion.
Conclusion: While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.