拉米夫定治疗前与治疗期间乙肝病毒YMDD变异研究

Study on YMDD mutation of hepatitis B virus before and after treatment with lamivudine

目的研究慢性乙型肝炎患者应用拉米夫定治疗前与治疗一年期间的乙肝病毒YMDD变异情况。方法103例接受拉米夫定治疗的慢性乙型肝炎患者,在开始治疗前和治疗第1、4、8个月以及1年时采集患者外周血,提取乙型肝炎病毒DNA,采用单核苷酸多态性分析方法,进行短核苷酸片段测序分析。结果乙型肝炎病毒DNA多聚酶区,使用拉米夫定治疗前,发生YVDD变异者1例,发生YIDD变异者2例;治疗第1月,发生YVDD变异者2例,发生YIDD变异者2例;治疗第4月,发生YVDD变异者3例,发生YIDD变异者4例;治疗第8月,发生YVDD变异者6例,发生YIDD变异者8例;治疗1年时,发生YVDD变异者11例,发生YIDD变异者13例。结论在进行拉米夫定治疗前,乙型肝炎病毒即有变异情况发生,随拉米夫定治疗变异率增加治疗1年时,乙型肝炎病毒发生变异率最高。

Objective To investigate the status of YMDD mutation of hepatitis B virus in chronic hepatitis B patients before treatment and one year after treatment. Methods Peripheral blood in 103 patients with chronic hepatitis B treated with Lamivudine was collected before treatment and a month, 4 months, 8 months and a year after treatment, DNA of hepatitis B virus was extracted and single nucleotide acid polymorphism was used for analyzing short nucleotide sequence. Results There were one mutation of YVDD and two mutations of YIDD in DNA polymerase of hepatitis B virus before treatment, two mutations of YVDD and two mutations of YIDD in the first month, three mutations of YVDD and four mutations of YIDD 4 months after treatment, six mutations of YVDD and eight mutations of YIDD 8 month after treatment, eleven mutations of YVDD and thirteen mutations of YIDD a year after treatment. Conclusion There were mutations in DNA polymerase of hepatitis B virus before treatment, compared to that a month, 4 months, 8 months after treatment, mutation rate in DNA polymerase of hepatitis B virus was highest a year after treatment with lamivudine.