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Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine
Author(s) -
Hatakeyama Tsuyoshi,
Noguchi Chiemi,
Hiraga Nobuhiko,
Mori Nami,
Tsuge Masataka,
Imamura Michio,
Takahashi Shoichi,
Kawakami Yoshiiku,
Fujimoto Yoshifumi,
Ochi Hidenori,
Abe Hiromi,
Maekawa Toshiro,
Kawakami Hiroiku,
Yatsuji Hiromi,
Aisaka Yasuyuki,
Kohno Hiroshi,
Aimitsu Shiomi,
Chayama Kazuaki
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21581
Subject(s) - lamivudine , entecavir , mutant , virology , medicine , hepatitis b virus , rna , reverse transcriptase , nucleoside , cccdna , virus , gastroenterology , biology , hbsag , gene , genetics
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. (H EPATOLOGY 2007;45:1179–1186.)