Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B: a double-blind, placebo-controlled trial.

Abstract

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.

• Authors: Henry Lik-Yuen Chan, Hao Wang, Junqi Niu, Angel Mei-Ling Chim, Joseph Jao-Yiu Sung
• Journal: Antiviral therapy (Antivir Ther) Vol. 12 Issue 3 Pg. 345-53 ( 2007) ISSN: 1359-6535 [Print] England
• PMID: 17591024 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Viral
• Hepatitis B e Antigens
• Reverse Transcriptase Inhibitors
• Lamivudine
• Alanine Transaminase

Topics

• Adolescent
• Adult
• Alanine Transaminase (blood)
• China
• DNA, Viral (blood)
• Double-Blind Method
• Drug Resistance, Viral (genetics)
• Endpoint Determination
• Female
• Hepatitis B e Antigens (metabolism)
• Hepatitis B virus (drug effects, genetics, immunology, isolation & purification)
• Hepatitis B, Chronic (blood, drug therapy, virology)
• Hong Kong
• Humans
• Lamivudine (pharmacology, therapeutic use)
• Male
• Middle Aged
• Reverse Transcriptase Inhibitors (pharmacology, therapeutic use)
• Time Factors
• Treatment Outcome