肝内乙型肝炎病毒DNA甲基化在核苷（酸）类似物停药复发中的作用研究

发布时间：2018-03-07 16:59

本文选题：乙型肝炎病毒　切入点：核苷（酸）类似物　出处：《福建医科大学》2013年硕士论文　论文类型：学位论文

【摘要】：目的：研究核苷（酸）类似物治疗后达到停药标准的慢性乙型肝炎患者在停药时肝内乙型肝炎病毒DNA甲基化状态，从表观遗传学的角度探讨核苷类似物停药复发的分子病毒学机制。方法：选择经核苷（酸）类似物治疗后达到停药标准（实现HBeAg血清转换、HBVDNA持续阴转后继续用药24~48周）的HBeAg阳性慢性乙型肝炎患者18例，进行肝组织活检，抽提肝内HBV DNA，对HBV DNA进行亚硫酸氢盐化处理，PCR扩增HBV的3个CpG岛，克隆后测序。对所有患者每4周随访1次，连续随访24周，观察停药后的病毒学应答情况，，根据病毒学应答情况分为持久应答组和停药复发组。分析比较停药复发组和持久应答组之间肝内HBV DNA甲基化状态的差异。同时观察两组间停药时血清HBsAg定量水平的差异。结果：停药时血清中HBsAg在停药复发组中的水平明显高于持久应答组，差异具有统计学意义（p=0.037）。停药时肝内HBV DNA载量在两组间无显著性差异（p0.05）。停药时两组间肝内HBV DNA甲基化状态无统计学差异（p0.05）。结论：核苷（酸）类似物停药时血清HBsAg水平越低越不易复发，可以作为停药复发的预测指标。停药时肝内HBV DNA载量及HBV DNA甲基化状态能否作为核苷（酸）类似物停药复发的预测指标需要进一步研究。
[Abstract]:Objective: to study the status of DNA methylation of hepatitis B virus (HBV) in the liver of patients with chronic hepatitis B (CHB) after nucleoside (acid) analogue therapy. To explore the molecular virological mechanism of nucleoside analogue recurrence from epigenetics. Methods: eighteen patients with HBeAg positive chronic hepatitis B who met the standard of withdrawal after treatment with nucleoside analogue (HBeAg seroconversion and continuous negative conversion of HBV DNA for 24 weeks) were selected for liver biopsy. HBV DNA was extracted from the liver and HBV DNA was treated with hydrogen sulfite to amplify the three CpG islands of HBV and sequenced. All patients were followed up once every 4 weeks and followed up for 24 weeks to observe the virological response after drug withdrawal. According to the virological response, the patients were divided into persistent response group and drug withdrawal recurrence group. The difference of intrahepatic HBV DNA methylation status between the two groups was analyzed and compared, and the difference of serum HBsAg level between the two groups was observed. Results: the level of serum HBsAg in the relapse group was significantly higher than that in the persistent response group. The difference was statistically significant. There was no significant difference in HBV DNA load between the two groups. There was no significant difference in the methylation status of HBV DNA between the two groups (p 0.05). Conclusion: the lower the serum HBsAg level of nucleoside analogue is, the more difficult it is to recur. The quantity of HBV DNA and the methylation of HBV DNA in liver could be used as predictors of recurrence of nucleoside analogue.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.62

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