Adefovir dipivoxil for treatment of breakthrough hepatitis caused by lamivudine-resistant mutants of hepatitis B virus.
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.
Hosaka
Tetsuya
T
Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan. hosa-p@toranomon.gr.jp
Suzuki
Fumitaka
F
Suzuki
Yoshiyuki
Y
Saitoh
Satoshi
S
Kobayashi
Masahiro
M
Someya
Takashi
T
Sezaki
Hitomi
H
Akuta
Norio
N
Tsubota
Akihito
A
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000188:drug therapy* / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
D016898:Interferon-alpha; D063065:Organophosphonates; D019259:Lamivudine; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil