A Comparison of the Efficacy and Safety of Entecavir Versus Lamivudine Through 240 Weeks of Treatment in Korean Patients with HBeAg-negative Chronic Hepatitis B

초록

Purpose: Long-term data on antiviral therapy in patients with HBeAg-negative chronic hepatitis B (CHB) are limited. We present the efficacy and safety of entecavir (ETV) compared with lamivudine (LAM) in treatment-naive Korean patients with HBeAg-negative CHB over 240 weeks. Methods: Patients were randomized to receive either ETV 0.5 mg/day or LAM 100 mg/day during the initial double-blind phase of 96 weeks, followed by open-label treatment through to Week 240. The primary objective was the proportion of patients with virologic response (VR, <300 copies/mL by PCR) at Week 24. Secondary objectives included ALT normalization (ALT ≤1 x ULN) and emergence of ETV resistance at Week 96, and proportion of patients with VR and mean reduction from baseline HBV DNA levels at Week 240. Safety data reported throughout the study included adverse events (AEs), serious AEs (SAEs), laboratory abnormalities and discontinuation due to AEs. Results: A total of 120 male and female patients (>16 years) were enrolled from 14 centers across Korea (ETV, n=56; LAM, n=64). There were no differences in baseline characteristics between the groups (Table). At Week 24, the proportion of patients with VR was significantly higher in the ETV group than in the LAM group (92.9% vs. 67.2%, p=0.0006), Week 96 (94.6% vs. 48.4%, p<0.0001) and Week 240 (95.0% vs. 47.6%, p<0.0001). At Week 96, ALT normalization was observed in 87.5% of ETV-treated and in 51.6% LAM-treated patients (p<0.0001), while virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (p<0.0001). Emergence of resistance to ETV was not detected. Mean reduction in HBV DNA from baseline to Week 240 was -3.61±0.76 and -2.45±1.54 log10 copies/mL with ETV and LAM, respectively (p<0.0001). Overall, 11 SAEs were reported in 7 ETV-treated patients while 20 SAEs were reported in 17 LAM-treated patients (p=0.055); however, these events were not related to either of the study medications. Conclusions: Long-term therapy with ETV offers advantages over LAM, with significantly higher proportions of HBeAg-negative CHB patients achieving virologic response and ALT normalization. Both treatments were well tolerated.