Lamivudine therapy for chronic hepatitis B: a six-month randomized dose-ranging study.
OBJECTIVE
Lamivudine inhibits hepatitis B virus replication. This study investigated 6 months of lamivudine treatment at three doses.


METHODS
Fifty-one patients (43% white, 49% Asian) with chronic hepatitis B were randomly assigned to receive 25, 100, or 300 mg of lamivudine orally once daily for 24 weeks with 24 weeks' follow-up.


RESULTS
Serum hepatitis B DNA by liquid hybridization decreased in all patients and was undetectable at the end of the treatment in 7 of 12 (58%, 25 mg), 13 of 14 (93%, 100 mg), and 14 of 16 (88%, 300 mg) patients. Of the 36 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 7 of 11 (64%, 25 mg), 5 of 11 (45%, 100 mg), and 5 of 14 (36%, 300 mg) normalized ALT at treatment completion. Quantitative decreases hepatitis Be antigen and hepatitis B surface antigen concentrations were observed at all doses. In most patients, markers of replication returned after treatment. Two patients (4%) were anti-HBe positive at the end of follow-up. Lamivudine was well tolerated. The incidence of adverse events was similar across all dose groups. However, 2 patients developed temporary hepatic decompensation after increase in transaminase levels after treatment.


CONCLUSIONS
Lamivudine was well tolerated and induced sustained suppression of hepatitis B replication during treatment in all patients at all doses. These data support investigation of longer treatment durations of 100 mg once daily.
Nevens
F
F
Department of Liver and Pancreas Diseases, University Hospital Gasthuisberg, Leuven, Belgium.
Main
J
J
Honkoop
P
P
Tyrrell
D L
DL
Barber
J
J
Sullivan
M T
MT
Fevery
J
J
De Man
R A
RA
Thomas
H C
HC
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001208:Asia / Q000208:ethnology; D004279:DNA, Viral / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005006:Ethnicity; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D013997:Time Factors
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase