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.
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
Tsubota
Akihito
A
Department of Gastroenterology, Toranomon Hospital, Minato-ku, Tokyo, Japan. ZUA05135@nifty.com
Arase
Yasuji
Y
Suzuki
Fumitaka
F
Kobayashi
Mariko
M
Matsuda
Marie
M
Sato
Junko
J
Suzuki
Yoshiyuki
Y
Akuta
Norio
N
Sezaki
Hitomi
H
Hosaka
Tetsuya
T
Someya
Takashi
T
Kobayashi
Masahiro
M
Saitoh
Satoshi
S
Ikeda
Kenji
K
Kumada
Hiromitsu
H
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
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine