拉米夫定治疗中国乙型肝炎患者中发现YMDD耐药变异株

DETECTION OF YMDD MUTANT IN CHINESE PATIENTS TREATED WITH LAMIVUDINE

为了监测拉米夫定临床治疗过程中耐药性的产生 ,更好地指导临床用药。采用 PCR产物克隆后测序的方法 ,对 2 0例服用拉米夫定病人进行随访观察 ,检测其体内乙型肝炎病毒 (HBV)聚合酶基因 (P gene) )酪氨酸 -蛋氨酸 -天门冬氨酸 -天门冬氨酸 (YMDD)区域变异情况 ,同时观察其 HBV DNA定量和肝功能指标变化。结果发现 ,1例病人在服用拉米夫定 9个月时出现 HBV YMDD变异株 ,并由混合感染逐渐进展为单一的变异株感染 ,出现耐药时伴有 HBV DNA定量反跳和 AL T的上升。表明拉米夫定长期治疗 (>6个月 )可能出现耐药 ,耐药变异株由弱势株逐渐演变为优势株 ,耐药出现时可伴有 HBV

With the method of clone sequencing, we analysed the seqnence of HBV polymerase gene YMDD motif in Chinese patients treated with lamivudine. HBV DNA quantitation and liver function parameters were also included in this study. We detected YMDD mutant in a patient after a nine month lamivudine therapy. The mutant virus became dominant after eleven months of therapy. The emergence of YMDD mutant was associated with HBV DNA rebound and ALT elevation.