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
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.
Hepatology. 2007 May;45(5):1179-86. doi: 10.1002/hep.21581.
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.
拉米夫定（LAM）是一种核苷类似物，广泛用于治疗慢性乙型肝炎病毒（HBV）感染。在接受拉米夫定治疗的患者中，逆转录酶酪氨酸-甲硫氨酸-天冬氨酸-天冬氨酸（YMDD）基序出现氨基酸替代的耐药毒株的出现是一个严重问题。据报道，出现YMDD突变体的患者血清中共价闭合环状DNA的量高于未出现突变体的患者。然而，在拉米夫定治疗期间，没有有用的血清标志物可以预测突变体的早期出现。对接受恩替卡韦治疗的患者（n = 7）和拉米夫定治疗的患者（n = 36）的分析表明，一些患者血清HBV RNA水平较高。YMDD突变体在1年内出现的患者（n = 6，1.688 log拷贝/ml）血清HBV RNA的中位数水平显著高于YMDD突变体在治疗1年后出现的患者（n = 12，0.456 log拷贝/ml，P = 0.0125）或YMDD突变体从未出现的患者（n = 18，0.688 log拷贝/ml，P = 0.039）。我们的结果表明，HBV RNA是拉米夫定治疗期间病毒突变早期发生的有价值的预测指标。
