Response to long-term lamivudine treatment in patients infected with hepatitis B virus genotypes A, B, and C.
Response to lamivudine treatment longer than 1 year was compared in 15 patients persistently infected with hepatitis B virus (HBV) genotype A, 38 with genotype B, and 449 with genotype C. Patients with genotype A were younger (median age 37 [range 24-49] vs. 47 [24-67] or 44 [18-73], P = 0.015), possessed hepatitis B e antigen (HBeAg) more frequently (73% vs. 21% or 56%, P < 0.001) and HBV DNA in higher levels (8.6 [6.1-8.7] vs. 6.5 [<3.7-8.7] or 6.5 [<3.7-8.7] log genome equivalents (LGE)/ml, P = 0.024) than those with genotype B or C. During lamivudine, YMDD mutants (89% vs. 53% or 42%, P = 0.0001) and breakthrough hepatitis developed more often (47% vs. 21% or 29%, P = 0.023) in patients with genotype A than B or C. YMDD mutants elicited more frequently in patients with genotype A than B or C who were positive (82% [9/11] vs. 25% [2/8] or 48% [117/245], P = 0.037) or negative for HBeAg (75% [3/4] vs. 30% [9/30] or 33% [68/204], P = 0.003). HBeAg (hazard ratio 2.1 [95% confidence interval 1.53-2.92], P < 0.001) and genotype A (2.78 [1.08-7.12], P = 0.034) enhanced the emergence of YMDD mutants by the Cox proportional hazard model. The risk for breakthrough hepatitis was increased by the baseline alanine aminotransferase level <500 IU/L (2.56 [1.82-5.50], P = 0.018), HBeAg (2.11 [1.40-3.16], P < 0.001), cirrhosis (1.92 [1.24-2.97], P = 0.004) and HBV DNA > or =8.0 LGE/ml (1.57 [1.04-2.36], P = 0.03); it was influenced by genotypes only in patients with HBeAg. In conclusion, HBV genotypes help in predicting response to long-term lamivudine treatment and development of YMDD mutants in patients with chronic hepatitis B.
Kobayashi
Mariko
M
Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan. vj7m-kbys@asahi-net.or.jp
Suzuki
Fumitaka
F
Akuta
Norio
N
Suzuki
Yoshiyuki
Y
Arase
Yasuji
Y
Ikeda
Kenji
K
Hosaka
Tetsuya
T
Sezaki
Hitomi
H
Kobayashi
Masahiro
M
Iwasaki
Satomi
S
Sato
Junko
J
Watahiki
Sachiyo
S
Miyakawa
Yuzo
Y
Kumada
Hiromitsu
H
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D016679:Genome, Viral; D005838:Genotype; D006515:Hepatitis B virus / Q000145:classification* / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006786:Hospitals, Urban; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016016:Proportional Hazards Models; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014041:Tokyo; D016896:Treatment Outcome
D005819:Genetic Markers; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine