Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine.
Lamivudine (LAM) is a nucleoside analogue widely used for the treatment of chronic hepatitis B virus (HBV) infection. Emergence of resistant strains with amino acid substitutions in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of reverse transcriptase is a serious problem in patients on LAM therapy. The amount of covalently closed circular DNA in the serum is reported to be higher in patients who develop YMDD mutants than in those without mutants. However, there is no useful serum marker that can predict early emergence of mutants during LAM therapy. Analysis of patients who were treated with entecavir (n=7) and LAM (n=36) showed some patients had high serum levels of HBV RNA. Median serum levels of HBV RNA were significantly higher in patients in whom the YMDD mutant had emerged within 1 year (n=6, 1.688 log copies/ml) than in those in whom the YMDD mutant emerged more than 1 year after treatment (n=12, 0.456 log copies/ml, P=0.0125) or in whom the YMDD mutant never emerged (n=18, 0.688 log copies/ml, P=0.039). Our results suggest that HBV RNA is a valuable predictor of early occurrence of viral mutation during LAM therapy.
Hatakeyama
Tsuyoshi
T
Department of Medicine and Molecular Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, and Department of Hepatology, Hiroshima Red Cross Hospital, Hiroshima-shi, Japan.
Noguchi
Chiemi
C
Hiraga
Nobuhiko
N
Mori
Nami
N
Tsuge
Masataka
M
Imamura
Michio
M
Takahashi
Shoichi
S
Kawakami
Yoshiiku
Y
Fujimoto
Yoshifumi
Y
Ochi
Hidenori
H
Abe
Hiromi
H
Maekawa
Toshiro
T
Kawakami
Hiroiku
H
Yatsuji
Hiromi
H
Aisaka
Yasuyuki
Y
Kohno
Hiroshi
H
Aimitsu
Shiomi
S
Chayama
Kazuaki
K
D000328:Adult; D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution; D015415:Biomarkers / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015336:Molecular Probe Techniques; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D015415:Biomarkers; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase