乙型肝炎病毒检测YMDD基序变异情况分析

Analysis of Hepatitis B Virus＇ YMDD Motif Mutations

目的调查乙肝患者HBVDNAYMDD基序突变情况，为医院肝病临床治疗前评估、优化治疗方案提供依据。方法收集2012年1月～7月间乙肝患者580份血清标本，进行HBVDNA检测和YMDD基序变异检测，并进行统计学分析。结果580份标本有351份血清中HBVDNA〉1×103 copies／ml，发生YMDD基序突变的血清为43份；不同病毒载量区间YMDD基序变异患者比例之间差异有统计学意义，YMDD基序变异患者分布与病毒载量高低存在负相关关系（卡方检验和Pearson相关性检验P均〈0．05）；高变异病毒载量的患者之一在接受ETV和ADV优化治疗3个月后，病毒栽量降至105copies／ml。结论YMDD基序变异会导致患者对NA类药物的敏感性降低，及时的基因突变检测能够对耐药进行预测，预防耐药发生，为肝病治疗方案的优化提供依据。

Objective To investigate YMDD motif mutation of Hepatitis B virus＇ DNA（HBV DNA） from patients in the 457th hospital,so as to provide evidence for the clinical treatment before the optimization scheme. Methods HBV DNA con- centration and YMDD motif mutation were detected by real-time PCR method in 580 serum samples, which were from pa- tients with newly diagnosed. The proportions of patients with the mutant HBV DNA in different concentration intervals were compared by use of the Chi-square test. The relationships between the proportion of patients with the mutant HBV DNA and HBV DNA concentration were assessed by use of the Pearson correlation. Results There were 351 serum samples in which HBV DNA concentration were greater than 1 X 103 copies/ml and 43 serum samples in which YMDD motif muta- ted. There were significant differences for the proportions among four concentration intervals （Xz = 37, 3, P^0.05）. Fur- thermore,the proportion were correlated with the HBV DNA concentration （P^0.05, r= --0. 312）. HBV DNA mutation caused the reduction of the DNA replication level. One of patients whose mutant Hepatitis B virus DNA concentration reached 10s copies/ml was receiving anti-viral treatment by taking nucleotide drugs of ETV and ADV for three months. DNA concentration of the patients was reduced to 10s copies/ml after treatment. Conclusion These findings suggest that YMDD motifmutation of HBV DNA could cause the sensitivity reduction of nucleoside analogue （NA）. Mutation detection should be carried out in a timely manner in the course of treatment for patients with hepatitis B, Drug resistance can be pre- dicted by mutation detection and correct assess. Therapy should continue to maintain therapy for patients with effective treatment programs. If not,therapy should change early for patients with primary nonresponse.