本文選題：肝炎 + 丙型�。� 參考：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：丙型肝炎病毒（hepatitis C virus，HCV）是慢性肝病的主要致病因素，目前感染者在全球達(dá)1.8億，感染率約為3％，我國人群抗-HCV陽性率為3.2％。丙型肝炎慢性化率為75％-85％，其中20％進(jìn)展為肝硬化，肝癌發(fā)生率為1％-4％，嚴(yán)重危害人類健康和生命。目前尚無預(yù)防HCV感染的有效疫苗，臨床標(biāo)準(zhǔn)治療方案為干擾素聯(lián)合利巴韋林，但其療程較長，副作用大，持續(xù)病毒學(xué)應(yīng)答（sustained virological response，SVR）率僅為38％-60％，仍有很大一部分患者病毒感染持續(xù)存在。HCV致病機(jī)制復(fù)雜，研究發(fā)現(xiàn)，HCV感染的不同臨床轉(zhuǎn)歸與某些細(xì)胞因子基因多態(tài)性相關(guān)。此外，機(jī)體的免疫狀態(tài)與慢性HCV感染/病毒學(xué)應(yīng)答的關(guān)系密切。與其他病毒感染一樣，HCV感染誘導(dǎo)激活了非特異性免疫應(yīng)答和特異性免疫應(yīng)答，在誘導(dǎo)和激活HCV特異性細(xì)胞免疫應(yīng)答中，Th1細(xì)胞扮演著重要的角色。 方法：選擇2012年1月~2013年9月在河北醫(yī)科大學(xué)第三醫(yī)院、石家莊市五院、邢臺市人民醫(yī)院、邯鄲市傳染病院住院及門診慢性丙型肝炎（chronic hepatitis C，CHC）患者256例，分別進(jìn)行IL-12基因多態(tài)性與相關(guān)因子的表達(dá)與疾病進(jìn)展及治療應(yīng)答的關(guān)系的研究。 1IL-12rs3212227基因多態(tài)性與HCV感染的關(guān)系CHC患者256例，健康體檢者129例作為對照，應(yīng)用TaqMan探針法檢測IL-12rs3212227位點(diǎn)基因多態(tài)性，分析CHC患者IL-12B等位基因、基因型分布與健康人群之間的差異。 2血漿IL-12、IL-10、IFN-γ水平與HCV感染狀況及治療應(yīng)答關(guān)系的研究CHC患者52例，年齡在18~65歲，干擾素聯(lián)合利巴韋林治療，療程為48周。另外選擇年齡、性別匹配的健康體檢者40例作為對照組，自發(fā)清除者40例，采用酶聯(lián)免疫吸附法（ELISA）檢測對照組、自發(fā)清除組及CHC患者治療前、治療12周和治療結(jié)束后隨訪24周時血漿IL-12、IL-10、IFN-γ水平，分析CHC患者與健康人群和自發(fā)清除者血漿IL-12、IL-10、IFN-γ之間的差異； 結(jié)果： 1IL-12B基因多態(tài)性檢測 CHC患者與健康對照等位基因A/C分布及基因型AA（32%vs38%）、AC（48%vs42%）、CC（20%vs20%）分布比較均無統(tǒng)計(jì)學(xué)意義（χ2=0.573，P=0.449）。256例CHC患者中95例進(jìn)行了基因型檢測，HCV基因1型與2型CHC患者等位基因A/C分布及基因型AA（37%vs20%）、AC（45.2%vs50%）、CC（17.8%vs30%）分布比較均無統(tǒng)計(jì)學(xué)意義（χ2=2.645， P=0.267）。隨訪結(jié)束的患者中，100例獲得SVR，60例未獲得SVR，獲得SVR和未獲得SVR患者等位基因A/C分布及基因型AA（37%vs27.4%）、AC（45%vs51.6%）、CC（18%vs21%）分布差異均無統(tǒng)計(jì)學(xué)意義（χ2=1.582， P=0.453）。 2IL-12、IL-10、IFN-γ血漿水平的變化 CHC患者抗病毒治療前基線血漿IL-12含量與健康對照組及自發(fā)清除組相比差異均具有統(tǒng)計(jì)學(xué)意義（P 0.001），自發(fā)清除組與健康對照組相比差異無統(tǒng)計(jì)學(xué)意義（P0.05）。獲得SVR與未獲得SVR患者相比，在基線、治療12周及治療結(jié)束后隨訪24周時獲得SVR患者IL-12水平顯著高于未獲得SVR組（P 0.001），且在治療過程中呈上升趨勢（P 0.001）；未獲得SVR患者在不同時間點(diǎn)IL-12血漿水平差異無統(tǒng)計(jì)學(xué)意義（P0.05）。CHC患者抗病毒治療前基線和自發(fā)清除組血漿IL-10含量均明顯高于健康對照組（P 0.001）。獲得SVR與未獲得SVR患者相比，，基線、治療12周及治療結(jié)束后隨訪24周獲得SVR顯著低于未獲得SVR患者（P 0.01，P 0.05，P 0.001），兩組在治療過程中血漿IL-10含量差異均無統(tǒng)計(jì)學(xué)意義（P0.05）。CHC患者抗病毒治療前基線血漿IFN-γ含量與健康對照組和自發(fā)清除組相比差異有統(tǒng)計(jì)學(xué)意義（P 0.001），自發(fā)清除組血漿IFN-γ含量顯著高于健康對照組（P 0.01）；獲得SVR與未獲得SVR患者相比，在治療12周及治療結(jié)束后隨訪24周時獲得SVR顯著高于未獲得SVR患者（P 0.001）；獲得SVR患者在治療過程中，IFN-γ含量呈上升趨勢（P 0.001）；未獲得SVR患者在不同時間點(diǎn)IFN-γ血漿水平差異無統(tǒng)計(jì)學(xué)意義（P0.05）。 結(jié)論： 1IL-12B基因多態(tài)性與HCV感染和預(yù)后可能無明確關(guān)系。 2CHC患者血漿IL-12和IFN-γ含量在抗病毒治療過程中升高，從而增強(qiáng)抗病毒免疫反應(yīng)，清除體內(nèi)的HCV，易獲得SVR。 3血漿IL-10水平可能為慢性HCV感染病毒自發(fā)清除的預(yù)測指標(biāo)之一。
[Abstract]:Objective: hepatitis C virus (HCV) is the main pathogenic factor of chronic liver disease. The infection rate is 180 million in the world and the infection rate is about 3%. The anti -HCV positive rate of the population in our country is 75%-85%, of which 20% is cirrhosis, and the incidence of liver cancer is 1%-4%, which seriously endangers human health. At present, there is no effective vaccine to prevent HCV infection. The clinical standard treatment scheme is interferon combined with Leigh Bhave Lin, but its course is long, the side effect is large and the rate of sustained virological response (SVR) is only 38%-60%. There are still a large part of the patient with the complicated pathogenesis of.HCV. In addition, the immune state of the body is closely related to the chronic HCV infection / virological response. As with other viral infections, the HCV infection induces the activation of non specific immune response and specific immune response, and the induction and activation of HCV specific cells in the induction and activation of HCV. In the immune response, Th1 cells play an important role.
Methods: to select 256 cases of chronic hepatitis C (chronic hepatitis C, CHC) patients in the Third Hospital of Hebei Medical University, the fifth hospital of Shijiazhuang, Xingtai People's Hospital, Xingtai People's Hospital, Handan infectious hospital and the patients with chronic hepatitis C (CHC) in the hospital of Shijiazhuang, January 2012, respectively, to express the expression of IL-12 gene polymorphism and related factors, and the relationship between the disease progression and the response to the treatment. A study of the Department.
1IL-12rs3212227 gene polymorphism was associated with HCV infection in 256 cases of CHC patients and 129 healthy subjects as control. TaqMan probe method was used to detect the polymorphism of IL-12rs3212227 loci, and the IL-12B alleles of CHC patients were analyzed, and the difference between genotype distribution and healthy population was found.
2 study on the relationship between plasma IL-12, IL-10, IFN- gamma and HCV infection status and response to treatment response in CHC patients, 52 cases of CHC, age at 18~65 years, interferon combined with Leigh Bhave Lin treatment, for 48 weeks. In addition, 40 cases of sex matched healthy persons were selected as control group, 40 cases were spontaneous cleaning, and enzyme linked immunosorbent assay (ELISA) was used to test control. Group, spontaneous scavenging group and CHC patients were treated for 12 weeks and IL-12, IL-10, IFN- gamma levels after 24 weeks of follow-up after treatment. The difference between CHC patients and IL-12, IL-10, IFN- gamma in healthy and spontaneous scavengers was analyzed.
Result錛

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