Long-term use of entecavir in nucleoside-naïve Japanese patients with chronic hepatitis B infection.
OBJECTIVE
To evaluate the long-term efficacy of entecavir in nucleoside-naïve chronic hepatitis B patients.


METHODS
One hundred and sixty-seven patients treated with entecavir 0.01mg, 0.1mg or 0.5mg for 24-52weeks in Phase II studies entered rollover study ETV-060 and received entecavir 0.5mg daily. Responses were evaluated among patients with available samples.


RESULTS
After 96weeks in ETV-060 (120-148weeks total entecavir treatment time), 88% (127/144) of patients had HBV-DNA <400 copies/ml; 90.1% (128/142) had alanine aminotransferase (ALT) 1x the upper limit of normal (ULN) among those with abnormal baseline ALT; and 26% (32/121) achieved HBe seroconversion among those HBeAg(+) at baseline. A subset of 66 patients received entecavir 0.5mg (approved dose) from Phase II baseline: at week 96 in ETV-060, 83% (48/58) had HBV-DNA <400 copies/ml, 88% (52/59) had ALT 1x ULN, and 20% (10/49) achieved HBe seroconversion. Twenty-one out of 66 patients had paired baseline and on-treatment biopsies: 100% (21/21) and 57% (12/21) demonstrated histologic improvement, and improvement in fibrosis, respectively, over 3years. The 3-year cumulative probability of resistance was 3.3% for all patients and 1.7% for the 0.5mg subset.


CONCLUSIONS
Long-term entecavir for nucleoside-naïve patients resulted in high rates of virological, biochemical, and histological response, with minimal resistance.
Yokosuka
Osamu
O
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
Takaguchi
Koichi
K
Fujioka
Shinichi
S
Shindo
Michiko
M
Chayama
Kazuaki
K
Kobashi
Haruhiko
H
Hayashi
Norio
N
Sato
Chifumi
C
Kiyosawa
Kendo
K
Tanikawa
Kyuichi
K
Ishikawa
Hiroki
H
Masaki
Nobuyuki
N
Seriu
Taku
T
Omata
Masao
M
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D044466:Asian People; D001706:Biopsy; D015331:Cohort Studies; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000208:ethnology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009705:Nucleosides; D013997:Time Factors; D016896:Treatment Outcome
D000998:Antiviral Agents; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D009705:Nucleosides; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase