[The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic resistance to adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B infection].
OBJECTIVE
Adefovir dipivoxil (ADV) is a nucleotide analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine (LMV)-resistant HBV mutants. The aim of this study was to elucidate the efficacy of ADV monotherapy and the incidence of genotypic resistance to ADV in patients with LMV-resistant chronic HBV infection.


METHODS
This study involved 124 patients with chronic HBV infection who had received ADV monotherapy due to the presence of LMV-resistant HBV mutants. The efficacy of ADV was evaluated by the normalization of serum alanine aminotransferase (ALT) level and by the reduction of serum HBV DNA level (with cutoff levels of 2x10(4) IU/mL and 2x10(2) IU/mL). The cumulative rate of HBeAg loss or seroconversion was assessed in HBeAg-positive patients. The development of mutations in the reverse trancriptase region of HBV DNA polymerase was evaluated by direct sequencing analysis during ADV monotherapy.


RESULTS
The mean serum HBV DNA level was 5.94 log10IU/mL. At 12 and 24 months after ADV monotherapy, the cumulative rates of serum ALT normalization were 69.4% and 75.5%, respectively, and those of serum HBV DNA reduction were 79.8% and 89.2% for a cutoff level of 2x10(4) IU/mL, and 44.2% and 59.0% for a cutoff of 2x10(2) IU/mL. The mean serum HBV DNA levels at 12 and 24 months were significantly lower than baseline, at 3.24 and 3.04 log10IU/mL, respectively (P<0.001). At 12 months after ADV treatment, the cumulative rates of HBeAg loss and seroconversion were 15.8% and 10.5%, respectively, and the rtN236T and rtA181T/V mutants in HBV DNA polymerase were identified in 25% and 64% of patients, respectively.


CONCLUSIONS
Although ADV monotherapy is effective, it leads to a high rate of mutations of HBV DNA reverse transcriptase gene in patients with chronic HBV infections who have LMV-resistant HBV mutants.
Moon
Jae Hyeon
JH
Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea.
Cho
Mong
M
Yoon
Ki Tae
KT
Bae
Jung Ho
JH
Heo
Jeong
J
Kim
Gwang Ha
GH
Kang
Dae Hwan
DH
Song
Geun Am
GA
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000032:analysis; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D063065:Organophosphonates / Q000627:therapeutic use*; D017422:Sequence Analysis, DNA
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D063065:Organophosphonates; D019259:Lamivudine; D004259:DNA-Directed DNA Polymerase; D000225:Adenine; C106812:adefovir dipivoxil