Clinical reactivation during lamivudine treatment correlates with mutations in the precore/core promoter and polymerase regions of hepatitis B virus in patients with anti-hepatitis B e-positive chronic hepatitis

A. Marrone, R. Zampino, P. Karayannis, G. Cirillo, G. Cesaro, B. Guerrera, R. Ricciotti, E. Miraglia Del Giudice, R. Utili, L. E. Adinolfi, G. Ruggiero

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Abstract

Background: Drug-resistant mutants may emerge in patients with chronic hepatitis B receiving lamivudine therapy. Aim: To evaluate whether different viral mutational patterns may be associated with clinical reactivation during lamivudine treatment in patients with chronic B hepatitis. Methods: Eight anti-hepatitis B e-positive patients with (group A) and 14 patients without clinical exacerbation (five anti-hepatitis B e-positive, group B1; nine hepatitis B e antigen-positive, group B2) during lamivudine treatment were investigated. Results: 'Polymerase region': M204V/1 variants were found in all group A patients, but in none of group B1 (P = 0.0007) and in four of nine of group B2 (44%; P = 0.02) patients. The L180M substitution was detected in four of eight (50%) of group A and in none of groups B1 and B2. 'Core promoter': the double basic core promoter (A1762T/G1764A) variant was detected in seven of eight (87%) of group A and in one of five (20%; P = 0.03) of group B1 and one of nine (11%; P = 0.002) of group B2 patients. 'Precore': the G1896A stop codon mutation was present in seven of eight (87%) of group A and in zero of five (P = 0.004) of group B1 and one of nine (11%; P -0.002) of group B2. Conclusions: Different mutational patterns were observed in the lamivudine-treated patients with and without exacerbation. There was an association of the basic core promoter and stop codon mutations with lamivudine resistance in patients with disease exacerbation.

Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalAlimentary Pharmacology and Therapeutics
Volume22
Issue number8
DOIs
Publication statusPublished - 15 Oct 2005
Externally publishedYes

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