Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine-resistant mutants of hepatitis B virus.

Abstract

OBJECTIVE:

Adefovir dipivoxil (ADV) is a nucleoside analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine-resistant HBV mutants in vitro and in vivo. The aim of this study was to evaluate the efficacy of ADV against lamivudine-resistant mutants and of adefovir and interferon (IFN) add-on to lamivudine for patients with severe acute exacerbation of hepatitis caused by lamivudine-resistant mutants.

METHODS:

Fourteen patients with breakthrough hepatitis were treated with ADV. Four of the 14 patients also received IFN as combined treatment for severe acute exacerbation of hepatitis.

RESULTS:

At week 24, serum HBV DNA levels had significantly decreased by a median of over 4.8 log copies/ml in the ADV group and over 5.9 log copies/ml in the ADV + IFN group compared to baseline. The median decrease in alanine aminotransferase (ALT) levels from baseline to week 24 was -1.05 times the upper limit of normal (ULN) in the ADV group [significant at week 24 compared with baseline (p = 0.012)] and -22.3 times the ULN in the ADV + IFN group.

CONCLUSIONS:

Administration of ADV add-on to lamivudine for patients with breakthrough hepatitis reduced HBV DNA and ALT levels. ADV and IFN add-on to lamivudine could prevent a fatal course in patients with severe acute exacerbation of hepatitis.

• Authors: Tetsuya Hosaka, Fumitaka Suzuki, Yoshiyuki Suzuki, Satoshi Saitoh, Masahiro Kobayashi, Takashi Someya, Hitomi Sezaki, Norio Akuta, Akihito Tsubota, Yasuji Arase, Kenji Ikeda, Hiromitsu Kumada
• Journal: Intervirology (Intervirology) Vol. 47 Issue 6 Pg. 362-9 ( 2004) ISSN: 0300-5526 [Print] Switzerland
• PMID: 15564749 (Publication Type: Journal Article)
• Copyright: 2004 S. Karger AG, Basel.

Chemical References

• Interferon-alpha
• Organophosphonates
• Lamivudine
• Alanine Transaminase
• Adenine
• adefovir dipivoxil

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Alanine Transaminase (blood)
• Drug Resistance, Microbial (genetics)
• Female
• Genotype
• Hepatitis B (drug therapy, virology)
• Hepatitis B virus (drug effects, physiology)
• Humans
• Interferon-alpha (administration & dosage, therapeutic use)
• Lamivudine (pharmacology)
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Safety
• Treatment Outcome