白介素12在慢性乙型肝炎病毒感染者血清和外周血单核细胞中的表达

乙型肝炎病毒在机体内的持续感染是由病毒和机体免疫状态两方面因素决定的。目前认为 ,机体能否最终清除病毒与体内免疫反应是以Ｔｈ1型为主还是以Ｔｈ2 型为主有关。Ｔｈ1型免疫反应能增强宿主抵抗微生物的感染 ,尤其是病毒与胞内感染 ,而Ｔｈ2 型免疫反应则与感染的进展、慢性化有关。白介素 12 (ＩＬ 12 )是抗原提呈细胞 (ＡＰＣ)产生的一种细胞因子 ,具有多种免疫活性。Ｇａｔｅｌｙ等[1] 认为ＩＬ 12在免疫反应中可诱导ＩＦＮ γ的产生和抑制ＩＬ 4的产生 ,从而诱导免疫反应朝着Ｔｈ1型方向发展 ,最终激活体内的细胞免疫。对象与方法一…     

白细胞介素12与慢性乙型肝炎

白细胞介素12(Ｉｎｔｅｒｌｕｋｉｎ－１２,ＩＬ－１２)是一种由单核吞噬细胞产生的细胞因子。它主要作用于细胞毒性T细胞(CTL)和自然杀伤细胞(NK),是迄今为止所发现的最有效的CTL和NK细胞活性刺激因子。目前研究认为,IL－１２能增强Ｔｈ１应答和抑制Ｔｈ2应答,在调控Ｔｈ细胞的分化上起重要作用。随着病毒性肝炎发病机理研究的不断深入,人们认为在乙肝病毒清除机制中,针对ＨＢV核衣壳抗原的T细胞反应起重要作用,ＨＢｃＡｇ/ＨＢｅＡｇ特异的Ｔｈ１和Ｔｈ2细胞亚群之间的平衡关系可能影响慢性化的产生和持续。ＨＢｃＡｇ和ＨＢ…     

肝炎后肝硬化患者外周血IL-10、IL-12的水平及其意义

目的　探讨IL -10、IL -12在肝炎后肝硬化中的作用及意义。方法　 3 4例肝炎后肝硬化患者根据Child -Pugh分级法分为A、B、C级三组 ,应用ELISA法检测外周血IL -10、IL -12水平 ,10例健康体检者作对照。结果　 3 4例肝炎肝后硬化患者有2 0例HBVDNA(+ ) ,HBVDNA(+ )组患者IL -10水平明显高于HBVDNA(-)组 (4 3 2 9± 18 66pg/mL、2 1 42± 9 47pg/mL ,P <0 0 1) ,而IL -12水平则低于HBVDNA(-)组 (92 45 + 2 9 73pg/mL、2 0 7 3 4± 83 61pg/mL ,P <0 0 1) ;肝硬化患者A级者IL -10水平稍高于对照组 (4 5 2 6± 9 43pg/mL、3 7 42± 5 61pg/mL ,P <0 0 5 )但显著高于B级和C级 (2 0 89± 7 46pg/mL、9 13± 0 2 4pg/mL ,P <0 0 1) ,且C级又明显低于B级 (P <0 0 1) ;肝硬化A、B、C级患者IL -12水平均低于对照组 (12 4 2 7± 5 0 14pg/mL、10 6 42± 49 0 6pg/mL、70 3 6± 2 0 62pg/mL ,2 15 64± 78 3 7pg/mL ,P <0 0 1) ,而以C级患者最低 (P <0 0 1)。结论　IL -10、IL -12可能在肝炎后肝硬化的发生发展中有一定作用     

IL-17在慢性乙型肝炎患者血清中的表达及其与肝炎肝硬化的相关性研究

目的研究IL-17在慢性乙型肝炎患者血清中的表达并探讨其与肝炎肝硬化的相关性。方法用双抗体夹心ELISA法测定34例慢性乙型肝炎、32例肝炎肝硬化、26例慢性重型乙型肝炎患者及20例健康对照者血清中的IL-17水平,同时检测不同Child-Pugh分级肝炎肝硬化患者血清IL-17的表达。结果各组患者与健康对照者血清IL-17的浓度均有显著性差异。肝硬化和慢性乙型肝炎组、重型肝炎组有显著差异(P<0.01),慢性乙型肝炎组与重型肝炎组之间无显著统计学差异(P=0.348);Child-PughB级、C级患者与A级患者相比,血清中IL-17的表达差异有显著统计学意义(P<0.01)。结论 IL-17与慢性乙型肝炎的发生以及肝纤维化之间可能有密切关系。     

环氧化酶-2在慢性乙型肝炎肝组织中的表达及意义

目的探讨慢性乙型肝炎患者肝脏组织中环氧化酶-2(COX-2)的表达及其临床意义。方法选择正常对照组10例,慢性乙型肝炎轻、中、重型各10例,肝硬化患者10例作为本实验的研究对象,应用SABC法分别对肝组织标本中COX-2测定,并结合病情轻重进行综合分析。结果慢性乙型肝炎组和肝硬化组肝组织中COX-2阳性率均明显高于对照组(P=0.0001),慢性乙型肝炎各组肝组织中COX-2含量存在显著的差异(P=0.0001)。结论 COX-2在慢性乙型肝炎和肝硬化的病理发展过程中起着一定的作用。     

乙型肝炎患者外周血单个核细胞IL-6 mRNA 表达的定量分析

目的 探讨IL-6参与乙型肝炎的免疫病理操作和病毒清除的机理。方法 采用ELISA法检定了慢性乙型肝炎（chronic hepatitis B.CHB）患者血清IL-6含量,竞争性RT-PCR-ELISA法分析了CHB外周血单个核细胞的IL-6 mRNA表达水平。结果 CHB血清IL-6含量明显升高,竞争性RT-PCR结果表明对照组和患者组IL-6mRNA靶片段表达频率分别为41.7%（5/12）和82.1(23/28）,定量ELISA表明5例对照组IL-6 mRNA拷贝数在1000-10000之间,平均拷贝数的对数为3.65;而患者组均大于10000,平均拷贝数的对数为4.40。 结论 IL-6在乙型肝炎发病中具有重要作用,而IL-6水平升高主要与患者外周血单个核细胞（peripheral blood monocyte cell,PBMC)IL-6 mRNA表达增加有关。     

慢性乙型肝炎患者血清IL-1β、IL-13与肝硬化的相关性

目的 分析血清白细胞介素-1β(IL-1β)、白细胞介素-13(IL-13)水平与慢性乙型肝炎(CHB)患者发生肝硬化的关系.方法 回顾性收集2017年10月至2020年1月南京中医药大学徐州附属医院消化内科接受治疗并完成随访的172例CHB患者的病例资料,其中86例发生肝硬化,作为观察组;另86例未发生肝硬化,作为对...     

白细胞介素-12受体与病毒性乙型肝炎的相关性研究进展

乙型肝炎为细胞内病原体感染性疾病,胞内感染性疾病的保护性免疫需要初始Th细胞向Th1细胞分化,白细胞介素-12受体(IL-12R)介导的JAK-STAT信号转导为Th1/Th2分化的重要途径.IL-12R减少或缺失导致Th1细胞的劣势分化,从而使乙型肝炎慢性化.因此深入研究IL-12R在乙型肝炎中的发病机制,有可能为其...     

延边地区朝鲜族乙型肝炎病毒感染者病毒基因型的检测与分析

目的:分析延边地区朝鲜族HBV感染者HBV基因类型分布及其临床意义.方法:延边地区朝鲜族HBV感染者215例分为无症状携带者36例,急性乙型肝炎5例,慢性乙型肝炎106例,肝炎肝硬化50例,原发性肝癌18例.利用特异性引物聚合酶链反应法(PCR),对患者血清标本进行基因型检测.结果:215例HBV感染者中检出B基因型61例(28.0%),C基因型154例(72.0%),未检出其他基因型.在慢性乙型肝炎、肝炎肝硬化、肝细胞癌患者中,C基因型比例(79.0%、84.0%、89.0%)明显高于无症状携带者及急性乙型肝炎(25.0%、60.0%,P<0.01),在无症状携带者中,B基因型比例高于C基因型(75.0%vs 25.0%,P<0.01).HbeAg阳性组C基因型比例高于HBeAg阴性感染组(73.0% vs 54.0%,P<0.05),HbeAg阴性组的B基因型比例高于HBeAg阳性组(46.0% vs 27.0%,P<0.01).结论:延边地区朝鲜族HBV感染主要为C基因型,其次为B基因型.C基因型在临床上以慢性乙型肝炎、肝炎肝硬化、肝细胞癌多见.其发生率显著高于B基因型.     

肝癌患者血清、癌组织中IL-6表达及其性别差异

目的观察肝细胞癌（肝癌）患者血清及癌组织中IL-6的表达及其性别差异。方法采用ELISA法检测不同性别肝癌患者术前及健康者外周血血清中的IL-6,免疫组化法检测肝癌组织中的IL-6。结果肝癌患者术前血清IL-6中位水平为4.82 pg/ml,健康者为2.31 pg/ml,两者比较,P〈0.01;男性肝癌患者血清IL-6水平为4.96pg/ml,女性为3.87 pg/ml,两者比较,P〈0.05。血清IL-6水平以3.51 pg/ml为cut-off值,诊断肝癌的敏感度与特异度分别为88.9%、87.5%;血清IL-6水平≥3.51 pg/ml者多为男性、肿瘤直径较大、血管内癌栓、肿瘤无包膜患者（P均〈0.05）。肝癌组织中IL-6阳性率为77%（69/90）,其中男性患者为84%（56/67）,女性患者为57%（13/23）,两者比较,P〈0.05。结论肝癌患者血清IL-6水平比正常健康者明显升高,男性肝癌患者血清及癌组织中IL-6的表达均高于女性患者。     

乙型肝炎肝硬化患者外周血IL-35和IL-17的表达及意义

目的观察慢性HBV感染者外周血IL-35和IL-17的表达和临床指标的相关性。方法采集30例慢性乙型肝炎（CHB）患者、79例乙型肝炎肝硬化（LC）患者、14例慢性乙型重型肝炎（CSHB）患者、20例健康对照者的外周血,ELISA法测定外周血IL-35、IL-6、IL-17的浓度,分离制备外周血单个核细胞（PBMC）,实时定量PCR检测PBMC中EBI3、FOXP3、IL-17 mRNA的表达,Western印迹观察PBMC中EBI3、FOXP3、IL-17蛋白表达情况。所有病例及健康对照均进行肝功能检测。结果 LC、CHB和CSHB患者中EBI3、IL-17、FOXP3 mRNA表达水平均显著高于健康对照组,差异有统计学意义（P〈0.01或0.05）;LC组Child-Pugh不同分级患者之间EBI3、IL-17、FOXP3 mRNA表达水平差异明显,EBI3、FOXP3 mRNA随着肝硬化Child-Pugh分级的加重而表达下调;IL-17 mRNA随着肝硬化Child-Pugh分级的加重而上调;蛋白表达和血清浓度的变化趋势与mRNA一致。血清IL-17浓度水平与Alb呈负相关,IL-17浓度水平与TBil、ALT和Child-Pugh分级呈正相关,差异有统计学意义（P〈0.01）,IL-35浓度水平与Alb、Child-Pugh分级负相关,与ALT、TBil无相关性。结论 IL-35和IL-17可能是影响乙型肝炎肝硬化发病的重要因素之一。     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1beta) promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC). METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1beta gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by chi2 test. RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P=0.036, OR=2.29, 95%CI=1.05-4.97) and patients without HCC (P=0.036, OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033, OR=1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups. CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

乙型肝炎和肝癌患者乙型肝炎病毒前C区1896位点突变的研究

为探索乙型肝炎病毒前Ｃ区突变是否与肝损程度及肝癌发生有关，对１３９例ＨＢｓＡｇ、ＨＢＶＤＮＡ和抗－ＨＢｅ阳性，ＨＢｅＡｇ阴性的慢性ＨＢＶ感染者和肝癌患者的血清标本，采用３＇碱基特异性聚合酶反应进行了第１８９６位核苷酸突变的检测分析。     

Interleukin-1β gene polymorphism associated with hepatocellular carcinoma in hepatitis B virus infection

AIM: To examine the effect of interleukin-1-beta (IL-1β)promoter region C-511T and IL-1 receptor antagonist (IL-1RN) polymorphism among the patients with chronic hepatitis B virus (HBV) infection (HCC and non-HCC).METHODS: Genomic DNA from 136 Thai patients with chronic HBV infection (HCC=46 and non-HCC=90) and 152 healthy individuals was genotyped for IL-1β gene polymorphism (-511) using polymerase chain reaction with sequence specific primers (PCR-SSP). The variable number of tandem repeats (VNTR) of IL-1RN gene was assessed by a PCR-based assay. The association between these genes and status of the disease was evaluated by X2 test.RESULTS: IL-1B-511 genotype C/C was found to be significantly different in patients with HCC when compared with healthy individuals (P = 0.036, OR = 2.29,95%CI = 1.05-4.97) and patients without HCC (P=0.036,OR=2.52, 95%CI=1.05-6.04). Analysis of allele frequencies of IL-1B-511 showed that IL-1B-511 C allele was also significantly increased in patients with HCC, compared to that in healthy control (P=0.033,OR= 1.72, 95%CI=1.04-2.84). However, no significant association in IL-1RN gene was found between the two groups.CONCLUSION: IL-1B-511C allele, which may be associated with high IL-1B production in the liver, is a genetic marker for the development of HCC in chronic hepatitis B patients in Thai population.     

白细胞介素-17肝内表达与慢性乙型肝炎病毒感染所致肝纤维化的相关性

Objective To explore the relationship between intrahepatic expression of interleukin-17 (IL-17) and liver fibrosis in patients with chronic hepatitis B virus infection. Methods IL-17 expressions in livers with different inflammation activity grades and hepatic fibrosis stages from patients with chronic hepatitis B virus carriers (n= 30), chronic hepatitis B (CHB, n = 55), liver cirrhosis (LC, n=20) were measured by immunohistochemistry. Serum IL-17 and liver fibrosis indices of haluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC Ⅲ ) and type Ⅳ collagen ( Ⅳ C) were determined by enzyme linked immunosorbent assay (ELISA). The differences between groups were compared by Kruskal-Wallis test, and the Mann-Whitney test, and the correlation analysis was done by Spearman test. Results Intrahepatic IL-17 expression in LC group was significantly higher than CHB group (x2 =25. 3982, P=0. 004), and that in CHB group was higher than chronic hepatitis B virus carriers group (x2 = 11. 5056, P= 0. 001). The inflammation activity grade and hepatic fibrosis stage were both positively correlated with IL-17 expression (r= 0.718, 0. 693, respectively; both P＜0.01). IL-17 mainly located in portal area and the expression was positively correlated with serum levels of HA, LN, PCⅢ and ⅣC (r=0. 793, 0. 834, 0. 722, 0. 883, respectively; all P＜0.01).Conclusion Intrahepatic IL-17 expression is closely correlated with liver inflammation activity grade and hepatic fibrosis stage.     

Studies of interleukin-12 in chronic hepatitis B virus infection

Summary. Interleukin-12 is produced by antigen-presenting cells and regulates the balance between TH₁/TH₂ lymphocyte subsets, promoting cell-mediated immune reactions. Amongst patients with chronic hepatitis B undergoing interferon-alpha treatment, only those who clear hepatitis B virus show a substantial increase in the production of biologically active IL-12 and an inverse ratio between serum levels of IL-12p40 subunit and IL-12. The peak of serum IL-12 occurs after the hepatitis flare and precedes or coincides with the time of HBe seroconversion. These data indicate that IL-12 is an important element for establishing the host immune control on hepatitis B virus replication in patients with chronic hepatitis B virus infection.     

白细胞介素-17肝内表达与慢性乙型肝炎病毒感染所致肝纤维化的相关性

Objective To explore the relationship between intrahepatic expression of interleukin-17 (IL-17) and liver fibrosis in patients with chronic hepatitis B virus infection. Methods IL-17 expressions in livers with different inflammation activity grades and hepatic fibrosis stages from patients with chronic hepatitis B virus carriers (n= 30), chronic hepatitis B (CHB, n = 55), liver cirrhosis (LC, n=20) were measured by immunohistochemistry. Serum IL-17 and liver fibrosis indices of haluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC Ⅲ ) and type Ⅳ collagen ( Ⅳ C) were determined by enzyme linked immunosorbent assay (ELISA). The differences between groups were compared by Kruskal-Wallis test, and the Mann-Whitney test, and the correlation analysis was done by Spearman test. Results Intrahepatic IL-17 expression in LC group was significantly higher than CHB group (x2 =25. 3982, P=0. 004), and that in CHB group was higher than chronic hepatitis B virus carriers group (x2 = 11. 5056, P= 0. 001). The inflammation activity grade and hepatic fibrosis stage were both positively correlated with IL-17 expression (r= 0.718, 0. 693, respectively; both P＜0.01). IL-17 mainly located in portal area and the expression was positively correlated with serum levels of HA, LN, PCⅢ and ⅣC (r=0. 793, 0. 834, 0. 722, 0. 883, respectively; all P＜0.01).Conclusion Intrahepatic IL-17 expression is closely correlated with liver inflammation activity grade and hepatic fibrosis stage.     

原发性肝癌和乙型肝炎肝硬化患者外周血淋巴细胞凋亡率、T细胞亚群和NK细胞的水平变化和临床意义

目的通过检测乙型肝炎肝硬化和合并乙型肝炎病毒感染的原发性肝细胞癌患者的外周血的粒细胞、单核细胞、NK细胞、T细胞及其亚群和淋巴细胞及其凋亡率,探讨两者在细胞免疫方面的差异.方法用Ficoll Hypaque离心法分离外周血单个核细胞(PBMNC),流式细胞仪检测外周血T细胞及其亚群、NK细胞和淋巴细胞、单核细胞和粒细胞,AnnexinV/FITCKit检测凋亡细胞.结果乙型肝炎肝硬化患者的外周血单核细胞、粒细胞、淋巴细胞、CD3-CD16 CD56 NK细胞、CD3 T细胞、CD3 CD4 T细胞、CD3 CD4 T细胞和CD4 CD8 T细胞比值,均与正常对照组无显著性差异(P＞0.05);但淋巴细胞凋亡率明显低于对照组(P＜0.01).原发性肝癌外周血CD3-CD16 CD56 NK细胞、单核细胞和CD4 /CD8 T细胞比值与肝硬化组和正常对照组比较,均无显著性差异(P＞0.05),而粒细胞明显升高(P＜0.05);CD3 T细胞、CD3 CD4 T细胞和CD3 CD8 T细胞均较另两组明显减少(P＜0.05),淋巴细胞及其凋亡率均明显低于另两组(P＜0.01).结论乙型肝炎肝硬化患者的外周血细胞免疫只发生不显著的变化,但淋巴细胞的凋亡率明显降低.原发性肝癌外周血的细胞免疫和淋巴细胞凋亡率均明显低下.     

慢性乙型肝炎病毒感染者肝细胞癌筛查和监测

肝细胞癌是我国常见恶性肿瘤,疾病负担十分沉重。筛查和监测是提高肝细胞癌患者早诊早治和生存率的有效措施。慢性乙型肝炎病毒感染是我国肝细胞癌的主要病因,有必要制定专门的筛查和监测策略。中国肝炎防治基金会组织国内有关专家,参考国内外相关指南,并结合当前研究进展和临床实践经验共同讨论后达成一致意见,旨在为规范开展慢性乙型肝炎病毒感染者肝细胞癌的筛查和监测提供参考,进而改善我国肝细胞癌的防控效果和患者预后。     

Hepatitis B genotypes： Relation to clinical outcome in patients with chronic hepatitis B in Saudi Arabia

INTRODUCTION Hepatitis B virus (HBV) infection is a global health problem with over 350 million chronic carriers of the virus with the risk of developing chronic hepatitis, cirrhosis or hepatocellular carcinoma (HCC). HBV is a circular, partially double-s…