Clinical and virological effects of long-term (over 5 years) lamivudine therapy.
Ideally, long-term lamivudine therapy should not induce tyrosine-methionine-aspartate-aspartate (YMDD) mutants (reverse transcription [rt]; rt M204I/V) in patients with chronic hepatitis B. There is little or no information on the clinical features of patients who do not develop such mutants. We analyzed 368 patients who received lamivudine therapy for more than 6 months between 1995 and 2003. Among them, 98 patients were negative for YMDD mutants during 5-year lamivudine therapy. Multivariate analysis identified hepatitis B e antigen (HBeAg) negativity, lack of cirrhosis, and high gamma glutamyltranspeptidase (GGTP) level as independent factors associated with lack of emergence of YMDD mutants during 5-year treatment. In these 98 patients, 21 patients developed YMDD mutants in the 5-year posttreatment follow-up. Old age was identified as the only factor associated with the emergence of YMDD mutants during that period. For all patients, 53 showed no elevation of alanine aminotransferase (ALT) or viral load after emergence of YMDD mutants during 5 years. Short latency to emergence of YMDD mutants, mixed (tyrosine-isoleucine-aspartate-aspartate (YIDD) [rtM204I] + tyrosine-valine-aspartate-aspartate (YVDD) [rtM204V]) type, and low ALT level were identified as independent factors associated with elevation ALT or viral load. HBeAg negativity, lack of cirrhosis, and high GGTP level were associated with lack of emergence of YMDD mutants during 5-year period. Young age protected against emergence of YMDD mutants over the 5-year period. Moreover, after the emergence of YMDD mutants, short latency to the emergence of YMDD mutant, mixed type mutants, and low baseline ALT level were associated with elevation of ALT or viral load.
Hashimoto
Yoshimasa
Y
Department of Hepatology, Toranomon Hospital, Minato-ku, Tokyo, Japan. y_hashimoto5327@yahoo.co.jp
Suzuki
Fumitaka
F
Hirakawa
Miharu
M
Kawamura
Yusuke
Y
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Hosaka
Tetuya
T
Akuta
Norio
N
Kobayashi
Masahiro
M
Saito
Satoshi
S
Suzuki
Yoshiyuki
Y
Kobayashi
Mariko
M
Arase
Yasuji
Y
Ikeda
Kenji
K
Kumada
Hiromitsu
H
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D016896:Treatment Outcome; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics; D055815:Young Adult
D000998:Antiviral Agents; D014764:Viral Proteins; D019259:Lamivudine; D000410:Alanine Transaminase; D012194:RNA-Directed DNA Polymerase