Long-term continuous entecavir therapy in nucleos(t)ide-naïve chronic hepatitis B patients.
OBJECTIVE
We determined the antiviral potency and viral resistance rate after 4 years of continuous entecavir treatment in patients with chronic hepatitis B (CHB) infection.


METHODS
The cumulative rates of undetectable hepatitis B virus DNA (HBV DNA;<2.6 log(10) copies/ml), hepatitis B e antigen (HBeAg) seronegativity, seroconversion, alanine aminotransferase (ALT) normalization, and entecavir signature mutations were calculated in 474 nucleos(t)ide-naïve CHB patients (HBeAg-positive: 47%) on continuous entecavir treatment for 4 years.


RESULTS
Median age was 47 years and follow-up period was 2.4 years, with 403, 281, 165, and 73 patients followed-up for at least 1, 2, 3, and 4 years, respectively. Incremental increases were observed in the rates of undetectable HBV DNA, HBeAg seroclearance and seroconversion, and ALT normalization, reaching 96%, 42%, 38% and 93%, respectively, by the fourth year. In all, 100% and 93% of patients negative and positive for HBeAg, respectively, had undetectable HBV DNA at year 4. Of 165 patients, HBV DNA was detectable in nine patients after 3 years. Multivariate analysis identified HBV DNA level (≤7.6 log(10) copies/ml, OR=15.8; 95% CI=43.1-79.9, P=0.001) as an independent predictor of undetectable HBV DNA at year 3. Five patients experienced virological breakthrough including two (0.4%) who developed entecavir-resistance mutations.


CONCLUSIONS
Continuous treatment of nucleos(t)ide-naïve CHB patients with entecavir over 4 years was associated with 96% chance of undetectable HBV DNA and only 0.4% chance of emerging entecavir-resistant mutations.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
Atsushi
A
Ono
Fumitaka
F
Suzuki
Yusuke
Y
Kawamura
Hitomi
H
Sezaki
Tetsuya
T
Hosaka
Norio
N
Akuta
Masahiro
M
Kobayashi
Yoshiyuki
Y
Suzuki
Satoshi
S
Saitou
Yasuji
Y
Arase
Kenji
K
Ikeda
Mariko
M
Kobayashi
Sachiyo
S
Watahiki
Rie
R
Mineta
Hiromitsu
H
Kumada
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D016001:Confidence Intervals; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D016017:Odds Ratio; D012189:Retrospective Studies; D013997:Time Factors; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase