title: Severe acute exacerbation of liver disease may reduce or delay emergence of YMDD motif mutants in long-term lamivudine therapy for hepatitis B e antigen-positive chronic hepatitis B.
abstract: The pretherapy factors that could influence the emergence of resistant hepatitis B virus (HBV) tyrosine-methionine-aspartate-aspartate (YMDD) motif mutants against lamivudine are not fully known in prolonged lamivudine therapy for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. We analyzed prospectively 116 consecutive lamivudine-naïve patients who received long-term lamivudine therapy (>1 year) by using multivariate regression analyses. The cumulative HBeAg loss rates were 29, 44, and 47% at 1, 2, and 3 years of treatment, respectively. Stepwise Cox's regression analyses indicated that pretherapy viral load was a significant factor associated with HBeAg loss (P = 0.0068). The cumulative emergence rates of YMDD mutants were 23% at 1 year, 45% at 2 year, and 47% at 3 year of treatment. Stepwise Cox's regression analyses indicated that patient age and presence or absence of severe acute exacerbation of liver disease were independent significant factors associated with emergence of YMDD mutants (P = 0.018 and 0.048, respectively). For the development of virological breakthrough, patient age, the presence or absence of severe acute exacerbation, and pretherapy viral load were independent significant factors (P = 0.028, 0.043, and 0.044, respectively). Severe acute exacerbation tended to reduce or delay development of biochemical breakthrough. The present study provides important information for the development of more effective and rational long-term lamivudine therapy for HBeAg-positive chronic hepatitis B patients infected exclusively with genotype
authors.affiliation: Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo, Japan. ZUA05135@nifty.com
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Marie
authors.initials: M
authors.lastname: Matsuda
authors.forename: Junko
authors.initials: J
authors.lastname: Sato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Someya
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D020816:Amino Acid Motifs; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine