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目的 探讨乙型肝炎病毒 (HBV)多聚酶酪氨酸 蛋氨酸 天冬氨酸 天冬氨酸 (YMDD)基序变异对拉米夫定抗病毒疗效的影响。方法 对 19例拉米夫定治疗 (10 0mg/d) 4 8周时血清病毒核酸阳性的慢性乙型肝炎患者 ,采用聚合酶链反应 (PCR)产物直接测序技术 ,检测其血清中HBV多聚酶 (YMDD)变异情况 ,并观察其血清HBVDNA和丙氨酸转氨酶 (ALT)水平。结果 在检出YMDD变异株的 10例患者中 (4例为YV550 DD型 ,均伴L52 6→M突变 ,6例为YI550 DD型 ) ,至 5 2周为止 ,共5例出现HBVDNA突发 (分枝DNA信号扩增法 ) ,其中 2例伴ALT再升高。追踪其治疗前血清均未发生上述变异。而在未检出YMDD变异的 9例患者中 ,1例出现DNA突发后又阴转 ,而另 1例治疗过程中HBVDNA未阴转、ALT始终波动于正常值上下的患者 ,发现多聚酶其他部位的变异 (G4 73 →R ,D4 77→N ,D4 80 →N ,L4 91→M )治疗前后相同。结论 乙型肝炎病毒多聚酶 (YMDD)变异与药物诱导相关 ,发生变异者较无变异者疗效降低 ;在拉米夫定治疗过程中 ,该变异的检测将有助于其疗效监测
Objective To investigate the effect of mutation of the tyrosine methionine aspartate aspartate (YMDD) motif on the antiviral efficacy of lamivudine in hepatitis B virus (HBV). The method of nucleic acid-positive serum viral patients with chronic hepatitis B during 48 weeks 19 cases lamivudine (10 0mg / d), polymerase chain reaction (PCR) direct sequencing products, and the serum of HBV polymerase ( YMDD), and observe the levels of serum HBV DNA and alanine aminotransferase (ALT). Results In 10 patients with YMDD mutation (4 patients were YV550 DD, all with L52 6 → M mutation and 6 patients were YI550 DD), up to 52 weeks, a total of 5 patients had HBVDNA burst Branched DNA signal amplification), of which 2 cases with elevated ALT. The above-mentioned mutations were not observed in all the patients before treatment. In 9 patients were not detected in the YMDD mutation, DNA burst after 1 patient overcast, one case and the other course of treatment is not HBVDNA overcast, the ALT normal patient always fluctuated up and down, the other parts of the polymerase found (G4 73 → R, D4 77 → N, D4 80 → N, L4 91 → M) were the same before and after treatment. Conclusion The hepatitis B virus polymerase (of YMDD) mutation associated with drug-induced, by mutation to reduce variability than those without effect; lamivudine treatment, the mutation detection will help monitor the efficacy