本文選題：慢性乙型肝炎病毒　切入點：抗病毒治療　出處：《吉林大學(xué)》2014年碩士論文

【摘要】：目的：檢測抗病毒治療過程中慢性乙型肝炎（CHB）患者外周血中的T、B、NK免疫細(xì)胞及其血清中細(xì)胞因子IL-2, IFN, TNF, IL-4, IL-6和IL-10的表達(dá)水平，并與肝臟功能及病毒載量之間進(jìn)行相關(guān)性分析，探討其對免疫應(yīng)答的影響。 方法：選取2010年9月至2012年10月就診于吉林大學(xué)第一醫(yī)院門診及入院的HBeAg陽性CHB患者，簽署知情同意后進(jìn)行篩選試驗，其中有54例應(yīng)用替比夫定初治療、30例對阿德福韋酯耐藥的患者轉(zhuǎn)用恩替卡韋治療，對照組為20例年齡、性別相匹配的健康人。通過流式細(xì)胞技術(shù)、微量樣本多指標(biāo)流式蛋白定量技術(shù)（Cytometric Bead Array，CBA）檢測各組CHB患者外周血中CD3-CD56+,CD244+NK, CD3+, CD3+CD4+, CD3+CD8+, CD4+CD25+Foxp3+, CD4+CD25+CD127low T, CD19+CD27+B細(xì)胞以及血清中CD4+T細(xì)胞相關(guān)的細(xì)胞因子（IL-2, IFN, TNF, IL-4, IL-6, IL-10）的含量。應(yīng)用羅氏公司全自動生化分析儀檢測ALT、AST的水平；應(yīng)用雅培公司化學(xué)發(fā)光分析儀檢測HBsAg、HBsAb、HBeAg、HBeAb；應(yīng)用熒光定量PCR方法檢測HBV DNA病毒載量的變化。分析治療前后各相應(yīng)免疫指標(biāo)與HBV DNA病毒載量、ALT、AST之間的相關(guān)性。 結(jié)果：初始應(yīng)用替比夫定治療的HBeAg陽性CHB患者組：(1) CHB患者經(jīng)替比夫定治療后，HBV DNA病毒載量、HBsAg乙肝表面抗原定量以及肝功ALT、AST水平較基線時呈下降趨勢，治療3月、6月、9月、13月后，以上各項指標(biāo)與基線及健康對照組相比，均明顯下降（P0.05）;在治療3月、6月、9月、13月后，分別有5、8、12、15例HBeAg陽性患者出現(xiàn)HBeAg血清學(xué)轉(zhuǎn)換;（2）CHB患者經(jīng)替比夫定治療后，CD3+CD4+、CD4+CD25+Foxp3+、 CD4+CD25+CD127lowT、CD8+PD-1+T細(xì)胞的絕對數(shù)呈下降趨勢，而CD3-CD56+、CD244+NK、CD3+CD8+T細(xì)胞的絕對數(shù)以及血清中CD4+T細(xì)胞分泌的細(xì)胞因子（IL-2, IFN,TNF, IL-4, IL-6，IL-10）的含量呈現(xiàn)上升趨勢;（3）CHB患者血清中CD4+T細(xì)胞相關(guān)的細(xì)胞因子（IL-2, IFN, TNF, IL-4, IL-6, IL-10）的水平與HBV DNA病毒載量以及肝功ALT、AST的水平呈明顯的負(fù)相關(guān)。 阿德福韋療效不佳轉(zhuǎn)用恩替卡韋治療的HBeAg陽性CHB患者組：（1）阿德福韋酯耐藥的CHB患者轉(zhuǎn)用恩替卡韋治療后，HBV DNA病毒載量、HBsAg乙肝表面抗原定量以及肝功ALT、AST水平較基線時呈下降趨勢，，治療3月、6月后，以上各項指標(biāo)與基線及健康對照組相比，均明顯下降（P0.05）;在治療3月、6月后，分別有4、11例HBeAg陽性患者出現(xiàn)HBeAg血清學(xué)轉(zhuǎn)換；（2）阿德福韋酯耐藥的CHB患者轉(zhuǎn)用恩替卡韋治療后，CD3+CD4+、CD4+CD25+Foxp3+、CD4+CD25+CD127lowT、 CD19+CD27+B細(xì)胞的絕對數(shù)呈下降趨勢，而CD3-CD56+、CD244+NK、CD3+CD8+T細(xì)胞的絕對數(shù)以及血清中CD4+T細(xì)胞分泌的細(xì)胞因子（IL-2, IFN, TNF, IL-4, IL-6）的含量呈現(xiàn)上升趨勢，而IL-10治療前后無明顯變化;（3）阿德福韋酯耐藥的CHB患者轉(zhuǎn)換為恩替卡韋治療后，血清中CD4+IFN+T細(xì)胞的水平與HBV DNA病毒載量以及肝功ALT、AST的水平呈明顯的負(fù)相關(guān)。 結(jié)論:1、CHB患者存在免疫耐受或者免疫功能低下的狀態(tài)；2、發(fā)現(xiàn)在抗病毒治療后CHB患者免疫細(xì)胞及細(xì)胞因子與未用藥前相比均有顯著的升高，表明核苷（酸）類似物可能通過免疫調(diào)節(jié)起到抑制病毒的作用；3、阿德福韋酯耐藥的CHB患者轉(zhuǎn)用恩替卡韋治療后取得較好的治療效果，表明恩替卡韋可以作為阿德福韋酯耐藥患者的替代治療；4、在抗病毒治療前后，CHB患者血清中CD4+T細(xì)胞分泌的細(xì)胞因子（IL-2, IFN, TNF, IL-4, IL-6、IL-10）的水平與HBV DNA以及肝功ALT、AST的水平具有一定的相關(guān)性，表明血清中細(xì)胞因子水平與抗病毒治療后病毒復(fù)制情況密切相關(guān)；5、CHB患者血清中CD4+T細(xì)胞分泌的細(xì)胞因子在抗病毒早期可以作為CHB患者治療過程中的一項臨床監(jiān)測指標(biāo)，為確定核苷酸類似物治療療程提供了新的思路，具有一定的臨床意義。
[Abstract]:Objective: chronic hepatitis B detection during antiviral treatment (CHB) in peripheral blood of patients with T, B, NK immune cells and cytokines in the serum of IL-2, IFN, TNF, IL-4, the expression level of IL-6 and IL-10, the correlation analysis between and liver function and viral load, to explore its effect on the immune response.
Methods: from September 2010 to October 2012 in No.1 Hospital of Jilin University from outpatient and hospitalized HBeAg positive CHB patients, informed consent after the screening test, the treatment of 54 cases of patients with early application of telbivudine, 30 cases of en to adefovir resistance of entecavir treatment, 20 cases in the control group age and gender matched healthy people. By flow cytometry, trace sample multivariate flow cytometry quantitative protein technology (Cytometric Bead Array, CBA) detection of CD3-CD56+, CHB in each group in the peripheral blood of patients with CD244+NK, CD3+, CD3+CD4+, CD3+CD8 + CD4+CD25+Foxp3+, CD4+CD25+CD127low, T, CD19+CD27+B cells and CD4+T cells in serum related cytokines (IL-2, IFN, TNF. IL-4, IL-6, IL-10). The contents of application of Roche automatic biochemical analyzer to detect the level of ALT, AST; application of chemiluminescence analyzer HBsA Abbott Company G, HBsAb, HBeAg, HBeAb; fluorescence quantitative PCR method was used to detect the changes of HBV DNA viral load. The correlation between the corresponding immune indexes before treatment and HBV DNA virus load, ALT and AST were analyzed.
Results: the HBeAg positive CHB patients in the initial application of telbivudine treatment: (1) CHB patients after telbivudine treatment, HBV DNA viral load, liver function and HBsAg quantitative hepatitis B surface antigen ALT, AST levels compared to the baseline treatment showed a downward trend, March, June, September, 13 months later, all the above indicators and baseline and compared to healthy controls, were significantly decreased (P0.05); in March June, September, treatment, 13 months later, there were 5,8,12,15 HBeAg positive patients with HBeAg seroconversion; (2) CHB patients treated with telbivudine treatment after CD3+CD4+, CD4+, CD25+Foxp3+, CD4+CD25+CD127lowT, the absolute number of CD8+PD-1+T cells decreased, while CD3-CD56+ CD244+NK, the absolute number of CD3+CD8+T cells and CD4+T cells in serum cytokines (IL-2, IFN, TNF, IL-4, IL-6, IL-10) content showed a rising trend; (3) CD4+T cytokines in the serum of patients with CHB related (I L-2, IFN, TNF, IL-4, IL-6, IL-10) level and HBV DNA viral load and liver ALT was significantly negative correlation between the level of AST.
HBeAg positive patients with CHB A Duff Vee to poor efficacy of entecavir therapy: (1) A Duff Vee ester resistant CHB patients switched to entecavir therapy after HBV DNA viral load, liver function and HBsAg quantitative hepatitis B surface antigen ALT, AST levels compared to the baseline treatment showed a downward trend, March, June, the above indicators with the baseline and compared to healthy controls, were significantly decreased (P0.05); the treatment in March, after June, there were 4,11 HBeAg positive patients with HBeAg seroconversion; (2) A Duff Vee ester resistant CHB patients switched to entecavir after treatment, CD3+CD4+, CD4+CD25+Foxp3+, CD4+CD25+CD127lowT, the absolute number of CD19+CD27+B cells was a downward trend, while CD3-CD56+, CD244+NK, the absolute number of CD3+CD8+T cells and CD4+T cells in serum cytokines (IL-2, IFN, TNF, IL-4, IL-6) content showed a rising trend, and IL-10 before and after treatment No obvious change; (3) patients with CHB conversion of adefovir resistant for entecavir treatment, the serum level of CD4+IFN+T cells and HBV DNA viral load and liver ALT was significantly negative correlation between the level of AST.
Conclusion: 1 CHB patients with immune tolerance or immunocompromised state; 2, found elevated in patients with CHB immune cells and cytokines and not significantly compared to before treatment in antiviral therapy, showed that the nucleoside (acid) analogues may inhibit the virus by immune function; 3, adefovir resistance to en CHB patients better treatment effect achieved after entecavir treatment, showed that entecavir can be used as an alternative treatment of adefovir resistant patients; in 4, before and after antiviral therapy, CD4+T cells secrete cytokines in the serum of patients with CHB (IL-2, IFN, TNF, IL-4, IL-6, IL-10) and HBV and DNA level liver ALT, AST levels have a certain correlation showed that the cytokine level and antiviral treatment in serum is closely related to HBV replication; 5, CD4+T cells secrete cytokines in the serum of patients with CHB In the early stage of antiviral therapy, it can be used as a clinical monitoring index in the treatment of CHB patients. It provides a new idea for determining the treatment course of nucleotide analogues, and has certain clinical significance.

【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R512.62

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相關(guān)期刊論文 前6條

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