title: Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine.
abstract: 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.
authors.affiliation: 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.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hatakeyama
authors.forename: Chiemi
authors.initials: C
authors.lastname: Noguchi
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.forename: Nami
authors.initials: N
authors.lastname: Mori
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Toshiro
authors.initials: T
authors.lastname: Maekawa
authors.forename: Hiroiku
authors.initials: H
authors.lastname: Kawakami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Aisaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kohno
authors.forename: Shiomi
authors.initials: S
authors.lastname: Aimitsu
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: 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
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D012367:RNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D012194:RNA-Directed DNA Polymerase