Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine: A 5-year study of patients with hepatitis B with lamivudine resistance

Fusao Ikeda, Nobuyuki Baba, Koichi Takaguchi, Junichi Kubota, Kenji Miyoshi, Shin Ichi Fujioka, Yuki Moritou, Yasuto Takeuchi, Tetsuya Yasunaka, Yasuhiro Miyake, Akinobu Takaki, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.0-8.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P=0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R=-0.38, P=0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV.

Original languageEnglish
Pages (from-to)1562-1570
Number of pages9
JournalJournal of Medical Virology
Volume84
Issue number10
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Lamivudine
Hepatitis B e Antigens
Viral DNA
Hepatitis B
Hepatitis B virus
DNA
Antigens
Therapeutics
adefovir dipivoxil
Mutation
RNA-Directed DNA Polymerase
Proportional Hazards Models
Multivariate Analysis
Observation

Keywords

  • Adefovir
  • Hepatitis B virus
  • Lamivudine resistance

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine : A 5-year study of patients with hepatitis B with lamivudine resistance. / Ikeda, Fusao; Baba, Nobuyuki; Takaguchi, Koichi; Kubota, Junichi; Miyoshi, Kenji; Fujioka, Shin Ichi; Moritou, Yuki; Takeuchi, Yasuto; Yasunaka, Tetsuya; Miyake, Yasuhiro; Takaki, Akinobu; Iwasaki, Yoshiaki; Kobashi, Haruhiko; Yamamoto, Kazuhide.

In: Journal of Medical Virology, Vol. 84, No. 10, 10.2012, p. 1562-1570.

Research output: Contribution to journalArticle

Ikeda, Fusao ; Baba, Nobuyuki ; Takaguchi, Koichi ; Kubota, Junichi ; Miyoshi, Kenji ; Fujioka, Shin Ichi ; Moritou, Yuki ; Takeuchi, Yasuto ; Yasunaka, Tetsuya ; Miyake, Yasuhiro ; Takaki, Akinobu ; Iwasaki, Yoshiaki ; Kobashi, Haruhiko ; Yamamoto, Kazuhide. / Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine : A 5-year study of patients with hepatitis B with lamivudine resistance. In: Journal of Medical Virology. 2012 ; Vol. 84, No. 10. pp. 1562-1570.
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abstract = "To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.0-8.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P=0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R=-0.38, P=0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV.",
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AU - Baba, Nobuyuki

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AU - Kubota, Junichi

AU - Miyoshi, Kenji

AU - Fujioka, Shin Ichi

AU - Moritou, Yuki

AU - Takeuchi, Yasuto

AU - Yasunaka, Tetsuya

AU - Miyake, Yasuhiro

AU - Takaki, Akinobu

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