Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial

Abstract

Background Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported. Aims This multicentre prospective randomized study was designed to compare the efficacy of these two strategies. Methods Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovirlamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months. Results One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovirlamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (=7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24. Conclusion This study showed that adefovirlamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.