Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B.
OBJECTIVE
Entecavir demonstrated superior benefit to lamivudine at 48 weeks in nucleoside-naive patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We evaluated continued entecavir and lamivudine treatment through 96 weeks.


METHODS
709 HBeAg-positive CHB patients were randomized to entecavir 0.5 mg (n = 354) or lamivudine 100 mg (n = 355) once daily. At week 52, protocol-defined virologic responders could continue blinded treatment for up to 96 weeks. Patients continuing in year 2 (entecavir, n = 243; lamivudine, n = 164) were assessed for serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT) normalization, HBeAg seroconversion, and safety. Cumulative confirmed proportions of all treated patients who achieved these responses were also analyzed.


RESULTS
Among patients treated in year 2, 74% of entecavir-treated versus 37% of lamivudine-treated patients achieved HBV DNA <300 copies/mL by polymerase chain reaction (PCR), and 79% of entecavir-treated versus 68% of lamivudine-treated patients normalized ALT levels. Similar proportions of entecavir-treated and lamivudine-treated patients achieved HBeAg seroconversion (11% vs 12%, respectively). Higher proportions of entecavir-treated than lamivudine-treated patients achieved cumulative confirmed HBV DNA <300 copies/mL by PCR (80% vs 39%; P < .0001) and ALT normalization (87% vs 79%; P = .0056) through 96 weeks. Cumulative confirmed HBeAg seroconversion occurred in 31% of entecavir-treated versus 25% of lamivudine-treated patients (P = NS). Through 96 weeks, no patient experienced virologic breakthrough due to entecavir resistance. The safety profile was comparable in both groups.


CONCLUSIONS
Entecavir treatment through 96 weeks results in continued benefit for patients with HBeAg-positive CHB.
Gish
Robert G
RG
Division of Hepatology and Complex GI, California Pacific Medical Center, San Francisco, California, USA.
Lok
Anna S
AS
Chang
Ting-Tsung
TT
de Man
Robert A
RA
Gadano
Adrian
A
Sollano
José
J
Han
Kwang-Hyub
KH
Chao
You-Chen
YC
Lee
Shou-Dong
SD
Harris
Melissa
M
Yang
Joanna
J
Colonno
Richard
R
Brett-Smith
Helena
H
D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000410:Alanine Transaminase