血清IL-21在各型慢性乙肝、肝硬化及肝衰竭中的作用及其临床意义

发布时间：2018-01-15 17:14

本文关键词：血清IL-21在各型慢性乙肝、肝硬化及肝衰竭中的作用及其临床意义　出处：《河北医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:乙型肝炎病毒(hepatitis B virus,HBV)感染是一个严重的公共卫生问题,全球60亿人口,约20亿人证明有HBV感染,其中3.5亿为慢性HBV感染[1]。据2006年全国乙型肝炎流行病学调查推算,我国现有的慢性HBV感染者约9300万人,其中慢性乙型肝炎患者约2000万例。因而对HBV的防治已成为中国健康与传染病控制中的首要问题。慢性乙型肝炎的发病机制十分复杂,一般认为HBV感染机体后的免疫应答主要通过CD4+T及CD8+T细胞介导,CD4+T及CD8+T细胞参与了HBV感染引起的肝细胞损伤,在疾病演变过程中发挥重要作用,对疾病的转归具有重要影响。IL-21是由多种活化的CD4+T细胞(主要为Th17细胞、滤泡性辅助性T细胞(Follicular Helper T cells,Tfh)等)、NK细胞分泌产生的细胞因子。IL-21可以通过增强CD8+T细胞的活化、增殖和效应功能调节细胞毒性的T淋巴细胞的分化。目前研究认为,IL-21在乙型肝炎的发病过程及疾病转归中起重要作用。本研究通过检测慢性乙型肝炎、乙型肝炎肝硬化、HBV相关性慢加急性肝衰竭患者血清中IL-21的变化,探讨血清IL-21在慢性乙型肝炎、肝硬化及肝衰竭中的作用及其临床意义。方法:研究对象为2013年12月至2014年12月河北医科大学第三医院、保定市传染病医院门诊及住院的患者共176例,包括慢性乙型肝炎患者89例(轻度31例、中度51例、重度7例)、HBV相关慢加急性肝衰竭36例、乙肝肝硬化失代偿期29例,乙肝肝硬化代偿期12例。176例中HBe Ag阳性90例,HBe Ag阴性86例,选择同期健康体检者10名作为健康对照组。常规检测血尿便常规、肝功能各项指标、凝血功能、HBV-DNA载量、乙肝五项、腹部B超或CT等,其中57例行肝组织病理检查;采用ELASA方法检测血清IL-21、IFN-γ含量,比较血清IL-21水平在各组的差异,并与肝功能、HBe Ag、HBV-DNA载量、肝脏组织病理变化、终末期肝病模型(model of end-stage liver disease,MELD)评分及预后作相关性分析。结果:1不同临床分型患者血清IL-21、IFN-γ水平分析慢性乙肝(轻度、中度、重度)、肝硬化代偿期、肝硬化失代偿期、慢加急性肝衰竭患者与健康对照组比较,血清IL-21及IFN-γ水平均明显升高,差别有统计学意义(P0.05);肝衰竭组较其他组升高明显,组间差别有统计学意义(P0.05);余各组之间差别无统计学意义(P0.05)。直线相关分析结果显示,患者血清中IL-21水平与IFN-γ有一定相关性,相关系数r=0.874,P0.05。2血清IL-21与肝细胞炎症之间的关系2.1血清IL-21与ALT关系:ALT5ULN组,血清IL-21明显高于ALT5ULN,差异有统计学意义(P0.05);其中ULNALT5ULN组血清IL-21较ALTULN组稍高,但差异无统计学意义。2.2血清IL-21与肝组织炎症分级的关系:根据57例慢乙肝患者肝组织病理结果分析得出,血清IL-21未随着肝脏炎症等级升高而升高,各组之间差异无统计学意义(P0.05)。3血清IL-21与肝组织纤维化的关系57例肝穿患者中有56例肝脏出现不同程度的纤维化,各组血清IL-21水平与肝脏纤维化分期无关(P0.05)。4血清IL-21与慢性乙肝重症化的关系4.1血清IL-21与TBIL、PTA、ALB、ALT的关系直线相关分析显示,IL-21与TBIL、PTA、ALT、ALB具有相关性,相关系数分别为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与慢加急性肝衰竭患者预后的关系36例慢加急性肝衰竭患者存活11例,死亡25例。肝衰竭患者死亡组血清IL-21较存活组稍高,但差异无统计学意义(P0.05)。4.3血清IL-21与MELD评分的关系MELD40组血清IL-21明显高于MELD≤40组,组间差异有统计学意义(P0.05);20MELD≤30组与30MELD≤40组比较差异无统计学意义(P0.05),40MELD≤50组与50MELD≤60组比较差异无统计学意义(P0.05)。 5血清IL-21与HBV复制的关系根据HBV载量不同分为HBV-DNA5log10copies/ml 60例,5≤HBV-DNA≤7log10copies/ml 69例,HBV-DNA7log10copies/ml 47例。统计学分析结果显示,三组之间两两比较血清IL-21水平差别无统计学意义(P0.05)。6血清IL-21与HBe Ag的关系176例患者中HBe Ag(+)90例,HBe Ag(-)86例。统计学分析结果显示,HBe Ag阳性组与阴性组比较血清IL-21水平差异无统计学意义(P0.05)。7血清IL-21与IFN-γ的关系直线相关分析结果显示,血清中IL-21水平与IFN-γ有一定相关性,相关系数r=0.874,P0.05。结论:1 IL-21在HBV感染后肝细胞损伤中起一定作用,可在一定程度上反映肝细胞损伤的严重程度,提示IL-21可能是HBV感染患者肝细胞受损的重要机制之一。2 MELD40组血清IL-21明显高于MELD≤40组,且与患者PTA呈明显负相关,提示IL-21可能与慢性乙肝重症化相关,是预测其预后的参考指标之一。3 HBe Ag的阳性表达与否及血清HBV-DNA含量的高低与患者血清IL-21含量无明显相关性,提示IL-21本身可能对HBV复制无明显作用。
[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.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R512.62;R575

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