Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B: a double-blind, placebo-controlled trial.
OBJECTIVE
We conducted a multicentre, double-blind, placebo-controlled, randomized study to investigate the efficacy of 2-year lamivudine treatment in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.


METHODS
One-hundred-and-thirty-nine treatment-naive patients with HBeAg-negative chronic hepatitis B were randomized to receive either lamivudine (100 mg daily) or placebo in a 2:1 ratio for 24 months and were followed for an additional 6 months. The primary endpoint was complete response, defined as hepatitis B virus (HBV) DNA < 10,000 copies/ml and normalization of alanine aminotransferase (ALT) levels at month 24.


RESULTS
On intent-to-treat analysis at month 24, significantly more patients in the lamivudine group than in the placebo group had complete response (56% and 11%, respectively; P < 0.001) or negative HBV DNA (26% and 6%, respectively; P = 0.006). After adjustment of baseline HBV DNA and ALT, the odds ratio for complete response of the lamivudine group versus the placebo group was 10.8 (95% confidence interval: 3.8-30.2; P < 0.001). The median log HBV DNA reduction was 3.21 copies/ml for the lamivudine group compared with 0.47 copies/ml for the placebo group (P < 0.001). Genotypic resistance was detected in 23% and 31% of patients in the lamivudine group at months 12 and 24, respectively. Negative HBV DNA at month 6 was associated with high complete response (84%) and low drug resistance (1%) at month 24. At month 30, there was no difference between lamivudine and placebo groups in the rates of complete response (26% vs 19%, respectively; P = 0.38) or negative HBV DNA (10% vs 2%, respectively; P = 0.09).


CONCLUSIONS
Two-year lamivudine treatment is effective in HBeAg-negative chronic hepatitis B. However, the response is not sustained after treatment cessation.
Chan
Henry Lik-Yuen
HL
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China. hlychan@cuhk.edu.hk
Wang
Hao
H
Niu
Junqi
J
Chim
Angel Mei-Ling
AM
Sung
Joseph Jao-Yiu
JJ
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D002681:China; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D024882:Drug Resistance, Viral / Q000235:genetics; D023381:Endpoint Determination; D005260:Female; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006723:Hong Kong; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase