乙型肝炎病毒基因变异的检测及相关因素的分析

Study on HBV YMDD Mutation and Its Correlation Factors

目的探讨乙型肝炎病毒基因变异与血清HBVDNA含量、ALT水平及拉米夫定治疗疗程的关系。方法采用荧光标记杂交双探针PCR融解曲线法，检测了148例经及未经拉米夫定治疗的慢性乙肝患者的HBV YMDD变异，同时观察HBV-DNA含量及谷丙转氨酶（ALT）水平的变化。结果经拉米夫定治疗12～24个月，YMDD变异的总检出率为24．7％，未经拉米夫定治疗的变异的检出率为5．6％，两组相比具有显著性差异（P〈0.01）。经拉米夫定治疗12、18及24个月，其血清HBVDNA含量及ALT水平明显低于用药前水平，差异具有显著性意义（P〈0.05）。拉米夫定治疗组中，发生变异者与未发生变异者，其用药前的HBVDNA含量及ALT水平无显著性差异（P〉0.05）。拉米夫定用药12、18、24个月的变异检出率分别为3．9％、15．6％、34．6％。结论乙型肝炎病毒P区存在YMDD自然变异，拉米夫定可促使病毒产生YMDD变异，其变异发生率随治疗时间的延长而明显增加。拉米夫定治疗有助于降低乙肝患者HBVDNA含量及ALT水平，拉米夫定引起的YMDD变异与用药前HBVDNA及ALT水平无明显的关系。

Objective To investigate HBV YMDD mutation and its relationship with the serum levels of HBV DNA , ALT and the duration of lamivudine treatment. Methods HBV YMDD mutations in 148 patients with chronic hepatitis B who were treated with or without lamivudine were detected by the fluorescent hybridization biprobe PCR and melting curve assay. The serum levels of HBV DNA and alanine aminotransferase （ALT） were also measured. Results The rate of HBV YMDD mutations in patients treated with lamivudine for 12 to 24 months or without was 24.7% and 5.6%, respectively, which had statistical significant difference（P〈0.01）.The serum levels of HBV DNA and ALT in patients with lamivudine treatment for 12,18 and 24 months were significantly lower than those in patients before the treatment（P〈0. 05）.No significant difference was found when compared the serum levels of HBV DNA and ALT, which is before the treatment, in patients with YMDD mutations with those in patients without mutations. The rates of HBV YMDD mutations were 3.9%, 15.6% and 34.6%, respectively, with the duration of lamivudine treatment of 12, 18 and 24 months. Conclusion The natural YMDD mutations occured spontaneously in patients without lamivudine treatment. Patients treated with lamivudine developed HBV YMDD mutations. The longer the treatment was continued, the more frequently mutation was found. The serum levels of HBV DNA and ALT reduced in patients with lamivudine treatment. The YMDD mutation had no significant relationship with the serum levels of HBV DNA and ALT which is before the treatment.