Efficacy of adefovir add-on lamivudine rescue therapy compared with switching to entecavir monotherapy in patients with lamivudine-resistant chronic hepatitis B

Authors

  • 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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  • 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. 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
    • Department of Internal medicine, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, Republic of Korea.
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  • Ryu H.J. and Lee J.M. contributed equally to this work.

  • The authors declare no competing interests.

Abstract

No study has reported on the comparative effect of adefovir (ADV) add-on lamivudine (LAM) versus switching to entecavir (ETV) in LAM-resistant patients with chronic hepatitis B. From October 2007 to September 2008, 92 consecutive LAM-resistant patients were enrolled (47 LAM + ADV and 45 ETV 1 mg). All patients were followed for at least 12 months. The parameters assessed included normalization of ALT, HBeAg seroconversion, undetectable HBV DNA, reduction of HBV DNA, and predictors of virologic response. In the LAM + ADV and ETV groups, the baseline DNA levels were 7.61 (5.19–9.49) and 7.10 (5.43–9.74) log10 copies/ml, respectively. At month 12, a virologic response occurred in 18/47 (38.3%) and 11/45 (24.4%; P = 0.182) patients; ALT normalization, in 39/41 (95.1%) and 36/40 (90.0%; P = 0.432); HBeAg seroconversion, in 5.1% and 2.4% (P = 0.606); and virologic breakthrough, in 2.1% and 11.1% (P = 0.107), respectively. The mean reduction from the baseline HBV DNA level was greater in the LAM + ADV group at month 12 (3.80 ± 1.12 vs. 2.72 ± 1.32 log10 copies/ml; P < 0.001). In the multivariate analysis, the independent parameters related to a virologic response at month 12 were baseline ALT (OR = 1.003, 95% CI = 1.000–1.006, P = 0.026) and baseline HBV DNA (OR = 0.495, 95% CI = 0.298–0.823, P = 0.007). Compared with switching to ETV monotherapy, ADV add-on LAM therapy was more effective at reducing the viral load in patients with LAM resistance, and the baseline HBV DNA and ALT levels were independent predictors of the virologic response. However, ADV add-on therapy had limitations in patients with a higher baseline HBV DNA in LAM rescue therapy. J. Med. Virol. 82:1835–1842, 2010. © 2010 Wiley-Liss, Inc.

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