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

Hyung Joon Yim, Yeon Seok Seo, Eileen L. Yoon, Chang Wook Kim, Chang Don Lee, Sang Hoon Park, Myung Seok Lee, Choong Kee Park, Hee Bok Chae, Moon Young Kim, Soon Koo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin Woo Lee, Sun Pyo Hong, Soon Ho Um

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13 Citations (Scopus)


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 adefovir-lamivudine 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 adefovir-lamivudine 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 adefovir-lamivudine 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.

Original languageEnglish
Pages (from-to)244-254
Number of pages11
JournalLiver International
Issue number2
Publication statusPublished - 2013 Feb

Bibliographical note

Funding Information:
Part of this study was supported by the Japan Society for the Promotion of Science KAKENHI (Grant Number: 23390168) and Projeto CSF-PVE's, Processo 88881.030.467/2013-01 (Brazil). We express our gratitude to the inhabitants of Taiji and Nachikatsuura who generously participated in this study.

All Science Journal Classification (ASJC) codes

  • Hepatology


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