Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B

Abstract

Background/aims: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks.

Methods: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation.

Results: In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (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% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications.

Conclusions: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.

Keywords: Entecavir; Hepatitis B; Lamivudine; Long-term effects.

Figure 1.

Flow diagram depicting the enrolment, allocation and progress of patients through the phases of the trial. HBV, hepatitis B virus; ETV, entecavir; LAM, lamivudine; ITT, intent-to-treat.

Figure 2.

Proportion of patients with virologic response (HBV DNA <300 copies/mL) at weeks 24, 96 and 240. P-values calculated using Pearson’s chi-square test (Weeks 24 and 96) or Fisher’s exact test (week 240). HBV, hepatitis B virus; ETV, entecavir; LAM, lamivudine.

Figure 3.

Mean log reduction in HBV DNA levels from week 1 to week 240 in ETV- and LAM-treated patients. HBV, hepatitis B virus; ETV, entecavir; LAM, lamivudine.