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. 2008 Sep;2(3):361-9.
doi: 10.1007/s12072-008-9081-2. Epub 2008 May 30.

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B

Satoshi Shakado  1 , Hiroshi Watanabe, Takashi Tanaka, Daisuke Morihara, Shinya Nishizawa, Shinjiro Inomata, Syuichi Ueda, Teruo Matsumoto, Akira Anan, Yasuaki Takeyama, Makoto Irie, Kaoru Iwata, Tetsuro Sohda, Shotaro Sakisaka
Affiliations

Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B

Satoshi Shakado et al. Hepatol Int. 2008 Sep.

Erratum in

  • Errata.
    Omata M, Sarin SK. Omata M, et al. Hepatol Int. 2008 Sep;2(3):395-6. doi: 10.1007/s12072-008-9089-7. Hepatol Int. 2008. PMID: 19669272 Free PMC article. No abstract available.

Abstract

Purpose: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment.

Methods: We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients.

Results: The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy.

Conclusions: Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.

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Figures

Fig. 1
Fig. 1
A follow-up study of liver histology on the patients with chronic hepatitis B treated with lamivudine. (a) Four patients whose alanine aminotransferase levels were more than 2 times the upper limit of normal showed no improvement in liver fibrosis at the second liver biopsy. (b) Nine patients whose alanine aminotransferase levels were less than 2 times the upper limit of normal demonstrated an improvement in liver fibrosis at the second liver biopsy even if the serum HBV DNA was positive. Another 3 patients whose degree of fibrosis was diagnosed to be F1 at the first liver biopsy showed no change in liver fibrosis
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