Evolution of Hepatitis B Virus Polymerase Gene Mutations in Hepatitis B e Antigen–Negative Patients Receiving Lamivudine Therapy

Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic he...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2000-11, Vol.32 (5), p.1145-1153
Main Authors: Suk-Fong Lok, Anna, Hussain, Munira, Cursano, Carmela, Margotti, Marzia, Gramenzi, Annagiulia, Luca Grazi, Gian, Jovine, Elio, Benardi, Mauro, Andreone, Pietro
Format: Article
Language:English
Subjects:
Adult
Aged
Biological and medical sciences
Cohort Studies
Drug Resistance, Microbial - genetics
Female
Gene Products, pol - genetics
Genotype
Hepatitis B e Antigens - analysis
Hepatitis B virus - genetics
Hepatitis B, Chronic - drug therapy
Hepatitis B, Chronic - genetics
Hepatitis B, Chronic - immunology
Hepatitis B, Chronic - virology
Human viral diseases
Humans
Infectious diseases
Lamivudine - therapeutic use
Male
Medical sciences
Middle Aged
Mutation
Promoter Regions, Genetic - genetics
Reverse Transcriptase Inhibitors - therapeutic use
Viral Core Proteins - genetics
Viral diseases
Viral hepatitis
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Summary:Lamivudine has been shown to be effective in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B, but its long-term efficacy and the rate of resistant mutations in patients with HBeAg-negative chronic hepatitis B is less clear. Twenty-nine patients with HBeAg-negative chronic hepatitis B, who have received lamivudine for at least 1 year were studied to determine the antiviral response, the rate and pattern of lamivudine-resistant mutations, and the effect of lamivudine-resistant mutations on HBeAg status. The mean duration of treatment was 21 ± 7 months. Before treatment, core promoter variant was detected in 16 (55%) patients and precore stop codon variant in 18 (62%) patients. Serum hepatitis B virus (HBV) DNA was detected by solution hybridization assay in 62%, 4%, and 24% and by polymerase chain reaction (PCR) assay in 100%, 31%, and 40% at months 0, 6, and 24, respectively. The cumulative rates of detection of lamivudine-resistant mutations after 1 and 2 years of treatment were 10% and 56%, respectively. In addition to the duration of treatment, core promoter mutation was associated with the selection of lamivudine-resistant mutants. Three patients with lamivudine-resistant mutations had reversion of the precore stop codon mutation; in 2 patients this was accompanied by the reappearance of HBeAg. We found that lamivudine-resistant mutants were detected at similar rates in patients with HBeAg-negative as in patients with HBeAg-positive chronic hepatitis B. Additional changes in other parts of the HBV genome may restore the replication fitness of lamivudine-resistant mutants. (Hepatology 2000;32:1145-1153.)
ISSN:0270-9139
1527-3350
DOI:10.1053/jhep.2000.19622