Virological response and hepatocarcinogenesis in lamivudine-resistant hepatitis B virus genotype C patients treated with lamivudine plus adefovir dipivoxil.
OBJECTIVE
The long-term efficacy of adefovir dipivoxil in combination with lamivudine to chronic hepatitis B virus (HBV) infection is still unclear.


METHODS
Virological response and hepatocarcinogenesis during lamivudine + adefovir were investigated in 183 lamivudine-resistant Japanese patients with chronic genotype C-dominant HBV infection. As the predictors of virological response, an assessment of clinical parameters and a nucleotide (nt) sequence analysis of the negative regulatory element to core gene (nt 1611-2450) were performed at the start of adefovir.


RESULTS
The cumulative HBV-DNA non-detectable and ALT normalization rates were 93.6 and 97.6% at the end of 3 years, respectively. Multivariate analysis identified total bilirubin, AST, and nt substitutions (nt 1762, 1768, 1846, 1896, 2134, 2288, 2441) as determinants of early non-detectable HBV-DNA. The yearly incidence of hepatocellular carcinoma (HCC) during the first 3 years was 2.7%. At the diagnosis of HCC, ALT normalization, HBV-DNA non-detectable, and HBeAg-seronegative conversion rates were 75.0, 83.3, and 57.1%, respectively. Furthermore, the cumulative HBV-DNA non-detectable and ALT normalization rates were not significantly different according to the development of HCC or not.


CONCLUSIONS
Lamivudine-resistant patients treated with lamivudine + adefovir could achieve the excellent virological response and biochemical response, but the low hepatitis activity was not enough to suppress hepatocarcinogenesis.
Akuta
Norio
N
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. akuta-gi@umin.ac.jp
Suzuki
Fumitaka
F
Kawamura
Yusuke
Y
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Suzuki
Yoshiyuki
Y
Hosaka
Tetsuya
T
Kobayashi
Masahiro
M
Kobayashi
Mariko
M
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006515:Hepatitis B virus / Q000187:drug effects*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000150:complications* / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016896:Treatment Outcome
D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D019259:Lamivudine; D000225:Adenine; C106812:adefovir dipivoxil