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

Authors

  • Hyung Joon Yim,

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
    • Correspondence

      Soon Ho Um, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seongbuk-gu, 136-705 Seoul, Korea

      Tel: +82 2 920 5019

      Fax: +82 2 953 1943

      e-mail: umsh@korea.ac.kr

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  • Yeon Seok Seo,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
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  • Eileen L. Yoon,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea
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  • Chang Wook Kim,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Catholic University of Korea Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
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  • Chang Don Lee,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Catholic University of Korea Uijeongbu St. Mary's Hospital, Uijeongbu, Korea
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  • Sang Hoon Park,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
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  • Myung Seok Lee,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea
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  • Choong Kee Park,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
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  • Hee Bok Chae,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea
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  • Moon Young Kim,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju Christian Hospital, Wonju, Korea
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  • Soon Koo Baik,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Yonsei University Wonju Christian Hospital, Wonju, Korea
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  • Yun Soo Kim,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea
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  • Ju Hyun Kim,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Gachon University Gil Hospital, Incheon, Korea
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  • Jung Il Lee,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea
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  • Jin Woo Lee,

    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Inha University Hospital, Incheon, Korea
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  • Sun Pyo Hong,

    1. GeneMarix Inc., Yongin, Korea
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  • Soon Ho Um

    Corresponding author
    1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
    • Correspondence

      Soon Ho Um, MD, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1 Anam-dong 5-ga, Seongbuk-gu, 136-705 Seoul, Korea

      Tel: +82 2 920 5019

      Fax: +82 2 953 1943

      e-mail: umsh@korea.ac.kr

    Search for more papers by this author

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 (= 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%, = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, < 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%, = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, = 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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