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Lamivudine plus adefovir vs. entecavir in HBeAg-positive hepatitis B with sequential treatment failure of lamivudine and adefovir

Authors

  • Chang Young Son,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
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    • Son C. Y. and Ryu H. J. contributed equally to this work.

  • Han Jak Ryu,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
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    • Son C. Y. and Ryu H. J. contributed equally to this work.

  • Jung Min Lee,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Department of Internal Medicine, CHA University, Seongnam-si, South Korea
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  • Sang Hoon Ahn,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
    3. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
    4. Brain Korea 21 Project for Medical Science, Seoul, South Korea
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  • Do Young Kim,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
    3. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
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  • Myoung Ha Lee,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
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  • Kwang Hyub Han,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
    3. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
    4. Brain Korea 21 Project for Medical Science, Seoul, South Korea
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  • Chae Yoon Chon,

    1. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
    2. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
    3. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
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  • Jun Yong Park

    Corresponding author
    1. Liver Cirrhosis Clinical Research Center, Seoul, South Korea
    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
    • Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
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Correspondence

Jun Yong Park, MD, Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea

Tel: 82 2 2228 1994

Fax: 82 2 393 6884

e-mail: DRPJY@yuhs.ac

Abstract

Background and Aims

Few studies have adequately examined the efficacy of lamivudine plus adefovir (LAM+ADV) combination therapy vs. entecavir (ETV) monotherapy in HBeAg-positive hepatitis B patients who fail to respond to sequential treatment with LAM and ADV. We compared directly the efficacy of LAM+ADV vs. ETV in such patients and assessed prognostic factors associated with a virologic response at month 12.

Methods

In total, 72 HBeAg-positive patients who showed resistance (n = 33) or a suboptimal virologic response (n = 39) to ADV monotherapy with resistance to LAM therapy underwent rescue therapy (31 LAM+ADV and 41 ETV). All patients were followed for at least 12 months.

Results

Following 12 months of treatment, in the LAM+ADV and ETV groups, a virologic response was observed in 7/31 (22.6%) and 8/41 (19.5%; P = 0.777) patients; ALT normalization occurred in 11/13 (84.6%) and 16/18 (88.9%; P = 0.566); HBeAg seroconversion in 1/31 (2.3%) and 4/41 (9.8%; P = 0.341) and a virologic breakthrough in 3/31 (9.0%) and 5/41 (12.1%; P = 0.452) respectively. Independent prognostic factors associated with a virologic response were the baseline HBV-DNA level (OR = 0.37; 95% CI 0.17–0.80; P = 0.011) and the duration of prior ADV monotherapy (OR = 0.89; 95% CI 0.83–0.95; P = 0.044).

Conclusions

Neither LAM+ADV nor ETV was adequately effective in patients with sequential LAM and ADV treatment failure. Thus, when chronic hepatitis B patients show resistance or suboptimal response to ADV monotherapy, early modification of treatment should be considered.

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