title: Correlation between pretreatment viral sequences and the emergence of lamivudine resistance in hepatitis B virus infection.
abstract: The emergence of amino acid or nucleotide substitutions leads to lamivudine resistance in hepatitis B virus (HBV) infected patients. The aim of this study was to investigate whether viral sequences help predict the emergence of lamivudine resistance. The study subjects comprised 59 consecutive patients infected with HBV treated with daily therapy of 100 mg lamivudine. Among those, 32 patients with adequate pretreatment serum preservation were investigated for the correlation between viral amino acid substitutions and the appearance of lamivudine resistance with consideration of clinical background by determining dominant HBV full open reading frames. Viral resistance to lamivudine emerged in 28 of 59 patients (47%) in a median period of 2.45 years. Sequence comparisons of HBV genomes between patients who later developed lamivudine resistance and patients who did not revealed the existence of significant differences between the two groups in the pre-S1 84 (P = 0.042), pre-S2 1 (P = 0.017) and 22 (P = 0.015), and polymerase tp 95 (P = 0.046), judged by a log-rank test. Viral sequence analyses revealed the presence of amino acid substitutions in HBV pre-S1 and pre-S2 that may be associated with the emergence of lamivudine resistance during chronic HBV infection.
authors: First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan.
authors: Ryota
authors: R
authors: Sueki
authors: Shinya
authors: S
authors: Maekawa
authors: Mika
authors: M
authors: Miura
authors: Makoto
authors: M
authors: Kadokura
authors: Kazuki
authors: K
authors: Komase
authors: Hiroko
authors: H
authors: Shindo
authors: Asuka
authors: A
authors: Kanayama
authors: Takako
authors: T
authors: Ohmori
authors: Kuniaki
authors: K
authors: Shindo
authors: Fumitake
authors: F
authors: Amemiya
authors: Yasuhiro
authors: Y
authors: Nakayama
authors: Tomoyoshi
authors: T
authors: Uetake
authors: Taisuke
authors: T
authors: Inoue
authors: Minoru
authors: M
authors: Sakamoto
authors: Nobuyuki
authors: N
authors: Enomoto
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D015684:Gene Products, pol / Q000235:genetics; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000201:enzymology / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D016366:Open Reading Frames; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
chemical_list: D004279:DNA, Viral; D015684:Gene Products, pol; C066027:P protein, Hepatitis B virus; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase