Effects of extended lamivudine therapy in Asian patients with chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.
OBJECTIVE
One-year lamivudine therapy significantly suppressed hepatitis B virus (HBV) replication, improved hepatic necroinflammatory activity, and prevented progression of fibrosis. However, the effects of prolonged therapy are unknown.


METHODS
A total of 334 Asian patients with chronic hepatitis B from a previously reported 1-year study were randomized to receive either lamivudine (100 or 25 mg) or placebo for another year. The effects of treatment on serum HBV-DNA suppression, alanine transaminase (ALT) normalization, and hepatitis B e antigen (HBeAg) seroconversion were measured. The presence of YMDD variant HBV and its effect were also determined.


RESULTS
A significantly greater proportion of patients achieved sustained HBV-DNA suppression and ALT normalization with 100 mg lamivudine daily for 2 years compared with lamivudine for 1 year followed by placebo for the second year (P<0.001). Daily lamivudine therapy for 2 years was safe and resulted in incremental HBeAg seroconversion from 17% at week 52 to 27% at week 104. HBeAg seroconversion during continued lamivudine therapy increased linearly with increasing pretherapy ALT levels (P< 0.001). Despite the emergence of YMDD mutant in 38% of the patients, they continued to clear serum HBeAg and maintain lower median serum HBV-DNA and ALT levels than baseline values. In contrast, ALT levels increased 8-12 weeks after switching from lamivudine to placebo, but returned to normal once lamivudine treatment was resumed.


CONCLUSIONS
Treatment with lamivudine for 2 years is both well tolerated and efficacious in patients with chronic hepatitis B.
Liaw
Y F
YF
Liver Research Unit, Chang Gung Memorial Hospital and University, Taipei, Taiwan. liveryfl@tp.silkera.net
Leung
N W
NW
Chang
T T
TT
Guan
R
R
Tai
D I
DI
Ng
K Y
KY
Chien
R N
RN
Dent
J
J
Roman
L
L
Edmundson
S
S
Lai
C L
CL
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D044466:Asian People; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000097:blood; D004334:Drug Administration Schedule; D005006:Ethnicity; D005260:Female; D006513:Hepatitis B e Antigens / Q000032:analysis / Q000235:genetics; D006515:Hepatitis B virus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D012016:Reference Values; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012698:Serologic Tests
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase