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目的 研究拉米夫定抗乙型肝炎病毒(HBV)感染中P基因发生YMDD变异的类型和出现时间。方法 取拉米夫定治疗过程中HBV DNA由阴性再次转为阳性33例患者及HBV DNA始终保持阳性达一年或一年以上2例患者的血清,经PCR扩增HBV的P基因,对扩增产物进行测序及用3个限制性内切酶分析HBVP基因的YMDD变异。 结果 14例出现YMDD变异,其中6例YVDD变异,4例YIDD变异,3例YI/VDD混合变异,1例YI/MDD变异。变异出现时间平均为(11.07±3.65)个月,最短5个月,最长7个月。其中YIDD为(10.00±1.41)个月,YVDD为(11.67±4.41)个月,YI/VDD为(13.33±3.31)个月,三种变异类型的出现时间差异无显著性(F=0.543,P>0.05)。3例YMDD变异后拉米夫定加量至200mg/d,未能消除变异病毒。 结论 拉米夫定抗HBV感染后变异有多种形式,包括YIDD、YVDD、YI/VDD、YI/MDD。变异发生时间一般在治疗后(11.07±3.65)个月。变异类型与用药时间无关。
Objective To study the type and timing of YMDD mutation of P gene in lamivudine against hepatitis B virus (HBV) infection. Methods Thirty-three patients whose HBV DNA turned negative again during the course of lamivudine treatment and the HBV DNA whose serum HBV DNA was always positive for one year or more than one year were obtained. The P gene of HBV was amplified by PCR, The amplified product was sequenced and the YMDD mutation of HBVP gene was analyzed by 3 restriction enzymes. Results YMDD mutation occurred in 14 cases, including 6 cases of YVDD mutation, 4 cases of YIDD mutation, 3 cases of YI / VDD mixed mutation and 1 case of YI / MDD mutation. The mean time of variation was (11.07 ± 3.65) months, the shortest was 5 months and the maximum was 7 months. The YIDD was (10.00 ± 1.41) months, the YVDD was (11.67 ± 4.41) months and the YI / VDD was (13.33 ± 3.31) months. There was no significant difference in the three types of variation (F = 0.543, P > 0.05). 3 cases of YMDD mutation lamivudine dosage to 200mg / d, failed to eliminate the mutant virus. Conclusion There are many variations of lamivudine after anti-HBV infection, including YIDD, YVDD, YI / VDD and YI / MDD. The time of variation is usually after treatment (11.07 ± 3.65) months. Variation types have nothing to do with medication time.