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, Moonyoung Kim, Soonkoo Baik, Yun Soo Kim, Ju Hyun Kim, Jung Il Lee, Jin Woo Lee, Sun Pyo Hong, Soon Ho Um

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 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
Volume33
Issue number2
DOIs
Publication statusPublished - 2013 Feb 1

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Lamivudine
Chronic Hepatitis B
varespladib methyl
Randomized Controlled Trials
Hepatitis B virus
Hepatitis B e Antigens
DNA
Multiple Drug Resistance
Antiviral Agents
entecavir
adefovir
Prospective Studies
Therapeutics
lamivudine-adefovir combination

All Science Journal Classification (ASJC) codes

  • Hepatology

Cite this

Yim, Hyung Joon ; Seo, Yeon Seok ; Yoon, Eileen L. ; Kim, Chang Wook ; Lee, Chang Don ; Park, Sang Hoon ; Lee, Myung Seok ; Park, Choong Kee ; Chae, Hee Bok ; Kim, Moonyoung ; Baik, Soonkoo ; Kim, Yun Soo ; Kim, Ju Hyun ; Lee, Jung Il ; Lee, Jin Woo ; Hong, Sun Pyo ; Um, Soon Ho. / Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study) : A 2-year follow-up randomized controlled trial. In: Liver International. 2013 ; Vol. 33, No. 2. pp. 244-254.
@article{574b52ef0a8641498498df8c0f31c918,
title = "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 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.",
author = "Yim, {Hyung Joon} and Seo, {Yeon Seok} and Yoon, {Eileen L.} and Kim, {Chang Wook} and Lee, {Chang Don} and Park, {Sang Hoon} and Lee, {Myung Seok} and Park, {Choong Kee} and Chae, {Hee Bok} and Moonyoung Kim and Soonkoo Baik and Kim, {Yun Soo} and Kim, {Ju Hyun} and Lee, {Jung Il} and Lee, {Jin Woo} and Hong, {Sun Pyo} and Um, {Soon Ho}",
year = "2013",
month = "2",
day = "1",
doi = "10.1111/liv.12036",
language = "English",
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pages = "244--254",
journal = "Liver International",
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Yim, HJ, Seo, YS, Yoon, EL, Kim, CW, Lee, CD, Park, SH, Lee, MS, Park, CK, Chae, HB, Kim, M, Baik, S, Kim, YS, Kim, JH, Lee, JI, Lee, JW, Hong, SP & Um, SH 2013, 'Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): A 2-year follow-up randomized controlled trial', Liver International, vol. 33, no. 2, pp. 244-254. https://doi.org/10.1111/liv.12036

Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study) : A 2-year follow-up randomized controlled trial. / Yim, Hyung Joon; Seo, Yeon Seok; Yoon, Eileen L.; Kim, Chang Wook; Lee, Chang Don; Park, Sang Hoon; Lee, Myung Seok; Park, Choong Kee; Chae, Hee Bok; Kim, Moonyoung; Baik, Soonkoo; Kim, Yun Soo; Kim, Ju Hyun; Lee, Jung Il; Lee, Jin Woo; Hong, Sun Pyo; Um, Soon Ho.

In: Liver International, Vol. 33, No. 2, 01.02.2013, p. 244-254.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study)

T2 - A 2-year follow-up randomized controlled trial

AU - Yim, Hyung Joon

AU - Seo, Yeon Seok

AU - Yoon, Eileen L.

AU - Kim, Chang Wook

AU - Lee, Chang Don

AU - Park, Sang Hoon

AU - Lee, Myung Seok

AU - Park, Choong Kee

AU - Chae, Hee Bok

AU - Kim, Moonyoung

AU - Baik, Soonkoo

AU - Kim, Yun Soo

AU - Kim, Ju Hyun

AU - Lee, Jung Il

AU - Lee, Jin Woo

AU - Hong, Sun Pyo

AU - Um, Soon Ho

PY - 2013/2/1

Y1 - 2013/2/1

N2 - 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.

AB - 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.

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