本文選題：乙型肝炎病毒　切入點：核苷（酸）類似物　出處：《福建醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：研究核苷（酸）類似物治療后達到停藥標準的慢性乙型肝炎患者在停藥時肝內(nèi)乙型肝炎病毒DNA甲基化狀態(tài)，從表觀遺傳學(xué)的角度探討核苷類似物停藥復(fù)發(fā)的分子病毒學(xué)機制。 方法：選擇經(jīng)核苷（酸）類似物治療后達到停藥標準（實現(xiàn)HBeAg血清轉(zhuǎn)換、HBVDNA持續(xù)陰轉(zhuǎn)后繼續(xù)用藥24~48周）的HBeAg陽性慢性乙型肝炎患者18例，進行肝組織活檢，抽提肝內(nèi)HBV DNA，對HBV DNA進行亞硫酸氫鹽化處理，PCR擴增HBV的3個CpG島，克隆后測序。對所有患者每4周隨訪1次，連續(xù)隨訪24周，觀察停藥后的病毒學(xué)應(yīng)答情況，，根據(jù)病毒學(xué)應(yīng)答情況分為持久應(yīng)答組和停藥復(fù)發(fā)組。分析比較停藥復(fù)發(fā)組和持久應(yīng)答組之間肝內(nèi)HBV DNA甲基化狀態(tài)的差異。同時觀察兩組間停藥時血清HBsAg定量水平的差異。 結(jié)果：停藥時血清中HBsAg在停藥復(fù)發(fā)組中的水平明顯高于持久應(yīng)答組，差異具有統(tǒng)計學(xué)意義（p=0.037）。停藥時肝內(nèi)HBV DNA載量在兩組間無顯著性差異（p0.05）。停藥時兩組間肝內(nèi)HBV DNA甲基化狀態(tài)無統(tǒng)計學(xué)差異（p0.05）。 結(jié)論：核苷（酸）類似物停藥時血清HBsAg水平越低越不易復(fù)發(fā)，可以作為停藥復(fù)發(fā)的預(yù)測指標。停藥時肝內(nèi)HBV DNA載量及HBV DNA甲基化狀態(tài)能否作為核苷（酸）類似物停藥復(fù)發(fā)的預(yù)測指標需要進一步研究。
[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.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.62

【共引文獻】

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