本文關(guān)鍵詞：血清IL-21在各型慢性乙肝、肝硬化及肝衰竭中的作用及其臨床意義　出處：《河北醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： IL-21 慢性乙型肝炎 乙肝肝硬化 慢加急性肝衰竭

【摘要】：目的:乙型肝炎病毒(hepatitis B virus,HBV)感染是一個(gè)嚴(yán)重的公共衛(wèi)生問(wèn)題,全球60億人口,約20億人證明有HBV感染,其中3.5億為慢性HBV感染[1]。據(jù)2006年全國(guó)乙型肝炎流行病學(xué)調(diào)查推算,我國(guó)現(xiàn)有的慢性HBV感染者約9300萬(wàn)人,其中慢性乙型肝炎患者約2000萬(wàn)例。因而對(duì)HBV的防治已成為中國(guó)健康與傳染病控制中的首要問(wèn)題。慢性乙型肝炎的發(fā)病機(jī)制十分復(fù)雜,一般認(rèn)為HBV感染機(jī)體后的免疫應(yīng)答主要通過(guò)CD4+T及CD8+T細(xì)胞介導(dǎo),CD4+T及CD8+T細(xì)胞參與了HBV感染引起的肝細(xì)胞損傷,在疾病演變過(guò)程中發(fā)揮重要作用,對(duì)疾病的轉(zhuǎn)歸具有重要影響。IL-21是由多種活化的CD4+T細(xì)胞(主要為T(mén)h17細(xì)胞、濾泡性輔助性T細(xì)胞(Follicular Helper T cells,Tfh)等)、NK細(xì)胞分泌產(chǎn)生的細(xì)胞因子。IL-21可以通過(guò)增強(qiáng)CD8+T細(xì)胞的活化、增殖和效應(yīng)功能調(diào)節(jié)細(xì)胞毒性的T淋巴細(xì)胞的分化。目前研究認(rèn)為,IL-21在乙型肝炎的發(fā)病過(guò)程及疾病轉(zhuǎn)歸中起重要作用。本研究通過(guò)檢測(cè)慢性乙型肝炎、乙型肝炎肝硬化、HBV相關(guān)性慢加急性肝衰竭患者血清中IL-21的變化,探討血清IL-21在慢性乙型肝炎、肝硬化及肝衰竭中的作用及其臨床意義。方法:研究對(duì)象為2013年12月至2014年12月河北醫(yī)科大學(xué)第三醫(yī)院、保定市傳染病醫(yī)院門(mén)診及住院的患者共176例,包括慢性乙型肝炎患者89例(輕度31例、中度51例、重度7例)、HBV相關(guān)慢加急性肝衰竭36例、乙肝肝硬化失代償期29例,乙肝肝硬化代償期12例。176例中HBe Ag陽(yáng)性90例,HBe Ag陰性86例,選擇同期健康體檢者10名作為健康對(duì)照組。常規(guī)檢測(cè)血尿便常規(guī)、肝功能各項(xiàng)指標(biāo)、凝血功能、HBV-DNA載量、乙肝五項(xiàng)、腹部B超或CT等,其中57例行肝組織病理檢查;采用ELASA方法檢測(cè)血清IL-21、IFN-γ含量,比較血清IL-21水平在各組的差異,并與肝功能、HBe Ag、HBV-DNA載量、肝臟組織病理變化、終末期肝病模型(model of end-stage liver disease,MELD)評(píng)分及預(yù)后作相關(guān)性分析。結(jié)果:1不同臨床分型患者血清IL-21、IFN-γ水平分析慢性乙肝(輕度、中度、重度)、肝硬化代償期、肝硬化失代償期、慢加急性肝衰竭患者與健康對(duì)照組比較,血清IL-21及IFN-γ水平均明顯升高,差別有統(tǒng)計(jì)學(xué)意義(P0.05);肝衰竭組較其他組升高明顯,組間差別有統(tǒng)計(jì)學(xué)意義(P0.05);余各組之間差別無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。直線相關(guān)分析結(jié)果顯示,患者血清中IL-21水平與IFN-γ有一定相關(guān)性,相關(guān)系數(shù)r=0.874,P0.05。2血清IL-21與肝細(xì)胞炎癥之間的關(guān)系2.1血清IL-21與ALT關(guān)系:ALT5ULN組,血清IL-21明顯高于ALT5ULN,差異有統(tǒng)計(jì)學(xué)意義(P0.05);其中ULNALT5ULN組血清IL-21較ALTULN組稍高,但差異無(wú)統(tǒng)計(jì)學(xué)意義。2.2血清IL-21與肝組織炎癥分級(jí)的關(guān)系:根據(jù)57例慢乙肝患者肝組織病理結(jié)果分析得出,血清IL-21未隨著肝臟炎癥等級(jí)升高而升高,各組之間差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3血清IL-21與肝組織纖維化的關(guān)系57例肝穿患者中有56例肝臟出現(xiàn)不同程度的纖維化,各組血清IL-21水平與肝臟纖維化分期無(wú)關(guān)(P0.05)。4血清IL-21與慢性乙肝重癥化的關(guān)系4.1血清IL-21與TBIL、PTA、ALB、ALT的關(guān)系直線相關(guān)分析顯示,IL-21與TBIL、PTA、ALT、ALB具有相關(guān)性,相關(guān)系數(shù)分別為r=0.631(P0.05)、r=-0.591(P0.05)、r=0.743(P0.05)、r=-0.276(P0.05)。4.2血清IL-21與慢加急性肝衰竭患者預(yù)后的關(guān)系36例慢加急性肝衰竭患者存活11例,死亡25例。肝衰竭患者死亡組血清IL-21較存活組稍高,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。4.3血清IL-21與MELD評(píng)分的關(guān)系MELD40組血清IL-21明顯高于MELD≤40組,組間差異有統(tǒng)計(jì)學(xué)意義(P0.05);20MELD≤30組與30MELD≤40組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05),40MELD≤50組與50MELD≤60組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。 5血清IL-21與HBV復(fù)制的關(guān)系根據(jù)HBV載量不同分為HBV-DNA5log10copies/ml 60例,5≤HBV-DNA≤7log10copies/ml 69例,HBV-DNA7log10copies/ml 47例。統(tǒng)計(jì)學(xué)分析結(jié)果顯示,三組之間兩兩比較血清IL-21水平差別無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。6血清IL-21與HBe Ag的關(guān)系176例患者中HBe Ag(+)90例,HBe Ag(-)86例。統(tǒng)計(jì)學(xué)分析結(jié)果顯示,HBe Ag陽(yáng)性組與陰性組比較血清IL-21水平差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。7血清IL-21與IFN-γ的關(guān)系直線相關(guān)分析結(jié)果顯示,血清中IL-21水平與IFN-γ有一定相關(guān)性,相關(guān)系數(shù)r=0.874,P0.05。結(jié)論:1 IL-21在HBV感染后肝細(xì)胞損傷中起一定作用,可在一定程度上反映肝細(xì)胞損傷的嚴(yán)重程度,提示IL-21可能是HBV感染患者肝細(xì)胞受損的重要機(jī)制之一。2 MELD40組血清IL-21明顯高于MELD≤40組,且與患者PTA呈明顯負(fù)相關(guān),提示IL-21可能與慢性乙肝重癥化相關(guān),是預(yù)測(cè)其預(yù)后的參考指標(biāo)之一。3 HBe Ag的陽(yáng)性表達(dá)與否及血清HBV-DNA含量的高低與患者血清IL-21含量無(wú)明顯相關(guān)性,提示IL-21本身可能對(duì)HBV復(fù)制無(wú)明顯作用。
[Abstract]:Objective: hepatitis B virus (hepatitis B, virus, HBV) infection is a serious public health problem, 6 billion of the world's population, about 2 billion people demonstrated HBV infection, including 350 million chronic HBV infection [1]. estimated 2006 national epidemiological survey of hepatitis B, chronic HBV existing infection in China about 93 million people, including patients about 20 million cases of chronic hepatitis B. Therefore prevention and treatment of HBV has become the most important issue China health and infectious disease control. The pathogenesis of chronic hepatitis B is very complex, generally considered immune response after HBV infection mainly through CD4+T and CD8+T cells mediated by CD4+T and CD8+T cells in the liver cell injury caused by HBV infection, play an important role in the evolution of the disease process, the outcome of the disease has the important effect of.IL-21 is caused by a variety of activated CD4+T cells (Th17 cells, follicular helper T cells The cell (Follicular Helper T cells, Tfh), etc.) NK cells secrete cytokines produced by.IL-21 can enhance the activation of CD8+T cells, differentiation and effector function regulation of the cytotoxic T lymphocytes. The present study suggests that the pathogenesis of the disease and the prognosis of IL-21 in hepatitis B plays an important role in this research. Through the detection of chronic hepatitis B, hepatitis B liver cirrhosis, chronic HBV associated changes of IL-21 in serum of patients with acute liver failure, serum IL-21 in chronic hepatitis B, cirrhosis and liver failure in the role and clinical significance. Methods: the research object from December 2013 to December 2014 the Third Hospital of Hebei Medical University, Baoding City infectious disease hospital outpatient and hospitalized patients in 176 cases, including 89 cases of chronic hepatitis B patients (31 mild cases, 51 moderate cases and 7 severe cases), HBV related acute on chronic liver failure in 36 cases, liver cirrhosis 29 cases of decompensated hepatitis B cirrhosis, 12 cases of.176 patients in HBe Ag HBe Ag was positive in 90 cases, 86 cases were negative, 10 healthy people were selected as healthy control group. Routine examination of urine routine, blood coagulation index, liver function, HBV-DNA load, hepatitis B five, abdominal ultrasound or CT, including 57 cases of liver biopsy; detection of serum IL-21 by ELASA method, IFN- gamma content, compare the serum IL-21 levels in different groups, and the liver function, HBe Ag, HBV-DNA, pathological changes of liver tissue, model for end-stage liver disease (model of end-stage liver disease, MELD) score and prognosis correlation analysis. Results: 1 patients with different clinical types of IL-21, IFN- levels analysis of chronic hepatitis B (mild, moderate, severe), decompensated cirrhosis, decompensated cirrhosis, acute on chronic liver failure patients compared with the healthy control group, serum IL-21 and IFN- gamma Levels were significantly increased, the difference was statistically significant (P0.05); liver failure group was higher than that in the other group, was statistically significant difference between the two groups (P0.05); no significant difference between the other groups (P0.05). Linear correlation analysis showed that there is a certain correlation between the level of IL-21 and IFN- in serum of patients with gamma, correlation coefficient r=0.874 2.1, IL-21 and ALT in serum between P0.05.2 serum IL-21 and hepatic inflammatory relationship: ALT5ULN group, serum IL-21 was significantly higher than that of ALT5ULN, the difference was statistically significant (P0.05); the serum IL-21 of ULNALT5ULN group is slightly higher compared with group ALTULN, but no significant differences in.2.2 serum IL-21 and liver histology: according to the 57 cases of liver tissues of patients with chronic hepatitis B and pathological results, serum IL-21 did not increase with the increase of liver inflammation grade, there was no significant difference between groups (P0.05).3 IL-21 in serum and liver fibrosis The relationship between the 57 cases of liver biopsy in 56 patients with varying degrees of liver fibrosis, the serum IL-21 level and liver fibrosis staging (P0.05) and IL-21 TBIL, 4.1.4 serum and serum IL-21 in chronic hepatitis B severe PTA, ALB, linear correlation analysis of the relationship between the ALT display, IL-21 and TBIL, PTA ALT, ALB, correlation, correlation coefficients were r=0.631 (P0.05), r=-0.591 (P0.05), r=0.743 (P0.05), r=-0.276 (P0.05).4.2 relationship between serum IL-21 and the prognosis of patients with acute on chronic liver failure, 36 cases of acute on chronic liver failure patients survived in 11 cases, 25 cases died. The serum IL-21 the survival group had slightly higher mortality in patients with liver failure, but there was no significant difference of serum IL-21 (P0.05).4.3 and MELD score between group MELD40 serum IL-21 was significantly higher than that of MELD group is less than or equal to 40, there was significant difference between the groups (P0.05); 20MELD group was no less than or equal to 30 and 30MELD is less than or equal to the difference between the 40 groups Meaning (P0.05), no statistically significant 40MELD = 50 group and 50MELD is less than or equal to the difference between the 60 groups (P0.05). The serum IL-21 5 and HBV replication relationship according to the HBV load is divided into 60 cases of HBV-DNA5log10copies/ml, 5 HBV-DNA 7log10copies/ml 69 cases, HBV-DNA7log10copies/ml 47 cases. Statistical analysis showed that between the three groups the level of IL-21 in serum of 22 No significant difference (P0.05) between.6 IL-21 and HBe Ag in serum of 176 patients in 90 cases of HBe Ag (+), HBe (- Ag) in 86 cases. The results of statistical analysis showed that there was no significant difference between HBe blood Ag positive group and negative group serum IL-21 level (P0.05) the relationship between linear correlation analysis results of.7 serum IL-21 and IFN- gamma shows that there is a certain correlation between the level of IL-21 and IFN- in serum gamma, correlation coefficient r=0.874. Conclusion: P0.05. plays a certain role in 1 IL-21 after HBV infection, liver cell injury, can reflect to a certain extent The severity of liver injury, suggesting that IL-21 may be an important mechanism of HBV infected liver cells.2 in patients with MELD40 group serum IL-21 was significantly higher than that of MELD group is less than or equal to 40, and significantly negative correlation with PTA in patients with chronic hepatitis B, suggesting that IL-21 may be severe, there was no significant correlation between the positive expression of prediction is one of.3 HBe Ag the index of the pre or not and the content of serum HBV-DNA level and serum IL-21 levels, suggesting that IL-21 itself may have no obvious effect on HBV replication.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R512.62;R575

【二級(jí)參考文獻(xiàn)】

相關(guān)期刊論文 前1條

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