Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy

Anna Suk-Fong Lok, Munira Hussain, Carmela Cursano, Marzia Margotti, Annagiulia Gramenzi, Gian Luca Grazi, Elio Jovine, Mauro Benardi, Pietro Andreone

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1145-1153
Number of pages9
JournalHepatology
Volume32
Issue number5
Publication statusPublished - 2000

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Lamivudine
Hepatitis B e Antigens
Hepatitis B virus
Mutation
Chronic Hepatitis B
Genes
Therapeutics
Terminator Codon
Mutation Rate
Antiviral Agents
Genome
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Hepatology

Cite this

Suk-Fong Lok, A., Hussain, M., Cursano, C., Margotti, M., Gramenzi, A., Luca Grazi, G., ... Andreone, P. (2000). Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy. Hepatology, 32(5), 1145-1153.

Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy. / Suk-Fong Lok, Anna; Hussain, Munira; Cursano, Carmela; Margotti, Marzia; Gramenzi, Annagiulia; Luca Grazi, Gian; Jovine, Elio; Benardi, Mauro; Andreone, Pietro.

In: Hepatology, Vol. 32, No. 5, 2000, p. 1145-1153.

Research output: Contribution to journalArticle

Suk-Fong Lok, A, Hussain, M, Cursano, C, Margotti, M, Gramenzi, A, Luca Grazi, G, Jovine, E, Benardi, M & Andreone, P 2000, 'Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy', Hepatology, vol. 32, no. 5, pp. 1145-1153.
Suk-Fong Lok, Anna ; Hussain, Munira ; Cursano, Carmela ; Margotti, Marzia ; Gramenzi, Annagiulia ; Luca Grazi, Gian ; Jovine, Elio ; Benardi, Mauro ; Andreone, Pietro. / Evolution of hepatitis B virus polymerase gene mutations in hepatitis B e antigen-negative patients receiving lamivudine therapy. In: Hepatology. 2000 ; Vol. 32, No. 5. pp. 1145-1153.
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