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...     

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。     

慢性乙型肝炎患者血清sICAM-1与IL-18变化及其临床意义

采用双抗体夹心ELISA法检测53例慢性乙型肝炎(CHB)患者血清可溶性细胞间黏附分子-1(sICAM-1)和白细胞介素-18(IL-18)水平,并与肝功能检查结果行相关性分析。结果:轻、中、重度CHB患者血清sICAM-1、IL-18水平均显著升高;重度CHB者显著高于中度,中度者显著高于轻度,P均<0.01;CHB患者血清IL-18水平与sICAM-1呈显著正相关,二者均与血清总胆红素(TB)、丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)呈显著正相关,与凝血酶原活动度(PTA)呈显著负相关。提示IL-18、sICAM-1参与了CHB的发生及转归;血清IL-18、sICAM-1水平可反映肝组织炎症活动及肝细胞损伤程度,对CHB的诊断、治疗及预后判断有一定价值。     

冠心病患者血清IL-6和IL-10水平检测的临床意义

目的探讨血清可溶性白细胞介素-6（IL-6）和白细胞介素-10（IL-10）水平与冠心病（CHD）病情及与冠状动脉病变程度的关系。方法将165例冠心病患者按临床诊断分为3组：急性心肌梗死（AMI）组60例、不稳定性心绞痛（UAP）组50例、稳定性心绞痛（SAP）组55例;健康对照组55例。用酶联免疫吸附试验检测各组血清可溶性IL-6和IL—10的水平,并比较各组间的差异。结果AM／组、UAP组及SAP组的血清可溶性IL-6和IL-10水平比对照组高（P〈0．05）,AMI组、UAP组血清IL-6水平高于SAP组（P〈0．05）;AMI组和UAP组血清IL-10水平低于SAP组（P〈0．05）;AMI组和UAP组血清IL-10的水平相似（P〉0．05）;结论冠心病患者血清可溶性IL-6及IL-10明显升高,且在一定程度上反映了病情、病变的严重程度,可作为CHD危险分层及病变程度评估的参考指标。     

自身免疫性甲状腺疾病患者血清IL-2和IL-4变化的临床意义

目的测定格雷夫斯病（GD）引起的甲状腺功能亢进症（GD甲亢）、格雷夫斯眼病（GO）、桥本氏甲状腺炎（HT）患者的血清IL-2和IL-4水平,探讨自身免疫性甲状腺疾病（AITD）患者Th1／Th2细胞失衡情况及其治疗后的变化。方法用放射免疫分析法检测30例正常对照组、70例GD甲亢初发未治组、62例GD甲亢治疗组、16例GO急性期组、18例GO慢性缓解期组、21例HT初发未治组和20例HT治疗组患者的血清IL-2和IL-4水平。结果与对照组比较,GD甲亢初发未治组和治疗组血清IL4均升高,治疗组与初发未治组比较无统计学差异;GO急性期血清IL-2和IL-4均明显升高,慢性缓解期IL-4升高,慢性缓解期较急性期IL-2降低;HT初发未治组和治疗组血清IL-2均明显升高。结论GD甲亢患者以Th2细胞免疫应答占优势,需要长期治疗,以免疾病复发;急性期GO患者的Th1和Th2细胞免疫应答强度均增加,慢性缓解期则以Th2细胞免疫应答占优势;HT患者的异常免疫以Th1细胞免疫应答占优势。     

食管癌患者血清IL-6、sIL-6R水平的监测及其临床意义

目的研究白细胞介素-6(IL-6)、可溶性IL-6受体(sIL-6R)在食管癌患者血清中的水平变化,以及IL-6与sIL-6R水平在肿瘤临床分期之间的相关关系,并探讨食管癌患者手术前后细胞因子水平的变化。方法用酶联免疫吸附试验(ELISA)方法检测了70例食管癌早期(Ⅰ~Ⅱ)患者、48例食管癌晚期(Ⅲ~Ⅳ)患者和130例对照者血清IL-6、sIL-6R水平,同时对118例食管癌患者手术前后的两项细胞因子指标进行动态观察。结果食管癌早期患者组和食管癌晚期患者组血清IL-6、sIL-6R水平均显著高于正常对照组(P<0.01),晚期患者较早期升高(P<0.01);食管癌转移组手术后血清IL-6、sIL-6R水平比手术前高(P<0.01),无转移组手术后两者水平较手术前明显降低(P<0.01),食管癌患者血清IL-6及sIL-6R水平与肿瘤的恶性化程度有明显相关性。结论sIL-6R在食管癌发病过程中可能起着促进作用,并可以与IL-6起协同作用,两者的免疫失调状态可能与食管癌密切相关;IL-6、sIL-6R水平可作为食管癌病情监测的指标,同时对肿瘤的临床分期、疗效和预后的判断也有一定的帮助。     

慢性乙型肝炎患者血清IL-18、IL-18BP水平及临床意义

目的探讨IL-18及其结合蛋白（IL-18BP）在慢性乙型肝炎（CHB）及乙肝后肝硬化（肝硬化）中的表达及意义。方法ELISA法检测30例CHB患者、63例乙肝后肝硬化患者血清中IL-18、IL-18BP及TB、ALT、AST、凝血酶原活动度（PTA）、C反应蛋白（CRP）水平，另设对照组20例。结果CHB及肝硬化患者IL-18BP水平均高于对照组，肝硬化患者IL-18水平亦高于对照组；IL-18水平与TB、CRP和AST呈正相关，与PTA呈负相关；IL-18BP与IL-18、TB、AST水平呈正相关，与PTA呈负相关。结论IL-18、IL-18BP参与了宿主对HBV的免疫应答，IL-18的作用受IL-18BP的调控。     

慢性乙型肝炎患者血清IL-10与HBVDNA复制水平检测及临床意义

检测慢性乙型肝炎 (CHB)患者血清IL - 10与HBVDNA、ALT水平 ,探讨乙型肝炎慢性化的机理。检测 77例CHB临床血清标本 ,用实时荧光定量聚合酶链反应 (FQ -PCR)测HBVDNA含量 ;用双抗体夹心ELISA法定量检测血清IL - 10水平。CHB患者血清IL - 10浓度明显高于正常对照组 (P <0 0 1) ,HBVDNA阳性组高于HBVDNA阴性组 ;CHB组患者血清ALT异常者的IL - 10浓度明显高于ALT正常组 ;IL - 10水平与HBVDNA复制程度呈正相关。CHB患者血清IL - 10水平升高与HBV持续感染、HBVDNA高复制合并肝损害有关。     

慢性乙型肝炎病毒携带者血清IL-1、IL-6和CRP水平与肝组织学相关研究

目的探讨慢性HBV携带者血清IL-1I、L-6和CRP水平与肝组织学变化的相关性。方法采用双抗体夹心ELISA法检测血清IL-1I、L-6;免疫比浊法检测血清CRP。采用在B超引导下快速肝穿刺活检术,肝组织炎症活动度分为轻度(G1-2/S0-2),中度(G3/S1-3),重度(G4/S2-4)。结果中、重度肝组织炎症活动者血清IL-1I、L-6和CRP水平显著高于轻度或无炎症改变者(P<0.05),轻度和无炎症改变者与正常对照组间比较无显著差异(P>0.05)。结论慢性HBV携带者血清IL-1I、L-6和CRP水平可以做为反应肝组织炎症活动程度的指标。     

血清胆碱酯酶与慢性乙型肝炎和肝硬化患者临床及病理的关系

目的 探讨血清胆碱酯酶(ChE)与慢性肝病患者的临床及病理的关系。方法随机选择105例慢性肝病患者，检测血清ChE活性，并行肝组织病理检查。结果肝病程度越重，ChE活性值降低愈明显，两者呈明显的负相关。肝组织炎症活动度及纤维化程度越高，血清ChE活性值降低愈明显，与病理损害程度呈明显的负相关关系。结论血清ChE可用于慢性肝病病情严重程度及预后的判断，血清ChE是观察慢性肝炎患者肝组织炎症及纤维化变化的较敏感指标。     

慢性乙型肝炎及肝硬化患者肝脏微循环改变

为探讨慢性乙型肝炎（慢乙肝）及肝硬化患者的肝脏微循环状态。对141例慢乙肝、12例肝硬化患者和2例正常人的肝组织进行HE染色,光镜观察,并对其中53例慢乙肝和2例肝硬化患者的肝组织进行了电镜观察。结果显示,正常人的肝窦腔通畅,无狭窄和闭塞,无红细胞聚集现象。慢乙肝患者86.52%有肝窦腔狭窄,60.28%肝窦腔内见红细胞聚集,34.04%肝窦腔内有血栓形成;电镜观察见94.34%的患者肝窦内皮细胞窗孔减小减少,33.96%有基底膜形成,24.53%狄氏腔内出现胶原纤维。肝硬化患者肝组织结构紊乱,肝腺泡消失,假小叶形成。提示慢乙肝患者存在肝脏微循环障碍,肝硬化时肝脏微循环结构丧失。     

瞬时弹性扫描检测慢性乙型肝炎患者肝纤维化的临床研究

目的:研究肝脏瞬时弹性检测仪(Fibroscan)在慢性乙型肝炎患者中的应用.方法:收集诊断为慢性乙型肝炎患者310例,其中包括23例慢性重型肝炎及65例肝硬化患者,使用Fibroscan检测肝脏硬度值,同时检测乙肝标志物HBV DNA、丙氨酸氨基转移酶、总胆红素水平.结果:慢性乙肝肝硬化患者的肝脏硬度值显著高于非肝硬化患者.肝脏重度炎症如重型肝炎,也可导致肝脏硬度值增大.年龄和性别因素可能对肝脏硬度值有影响.结论:Fibfroscan是评价慢性乙肝患者肝脏纤维化程度和诊断肝硬化的有效方法.在对个体病例进行分析时,需要考虑年龄和性别、肝脏炎症因素对肝脏硬度值的影响.     

慢性乙型肝炎并发肝硬化的转归研究

目的研究慢性乙型肝炎(CHB)远期并发代偿性和失代偿性肝硬化的概率和预示肝硬化发生的危险因素,分析CHB肝脏炎症分级、纤维化分期与发生肝硬化的关系。方法选取经临床病理确诊的382例CHB患者,包括HBeAg阳性者262例,HBeAg阴性者120例,随访肝硬化的发生率。采用Cox生存分析统计代偿性和失代偿性肝硬化发生的危险因素。结果平均随访88.64周后,75例(19.6%)发生代偿性肝硬化,年发生率0.90%;32例(8.4%)进展为失代偿性肝硬化,年发生率0.39%。262例HBeAg阳性CHB患者中48例(18.3%)发生代偿性肝硬化,年发生率0.84%,18例(6.87%)进展为失代偿性肝硬化,年发生率0.32%。120例HBeAg阴性CHB患者中27例(22.5%)发生代偿性肝硬化,年发生率1.01%,14例(11.61%)进展为失代偿性肝硬化,年发生率0.54%。HBeAg阴性CHB与HBeAg阳性CHB的代偿性和失代偿性肝硬化发生率之间均无统计学差异。肝脏纤维化分期为CHB发生代偿性和失代偿性肝硬化的危险因素(P<0.01),纤维化每增加1期,发生代偿性肝硬化的危险度增加2.14倍(HR:2.14,95%CI:1.67~2.75),发生失代偿性肝硬化的危险度增加1.70倍(HR:1.70,95%CI:1.22~2.36);炎症分级不是其危险因素。结论CHB患者代偿性肝硬化年发生率为0.90%,失代偿性肝硬化年发生率为0.39%,HBeAg阴性CHB和HBeAg阳性CHB肝硬化发生率之间差异无统计学意义。肝脏纤维化分期的严重程度与代偿性和失代偿性肝硬化的发生密切相关。     

持续ALT正常乙型肝炎肝硬化的肝功能及组织病理临床分析

目的 了解ALT持续正常的乙型肝炎肝硬化的肝功能、HBeAg、HBV DNA及肝组织炎症状况,探讨其临床特点.方法 收集ALT持续12个月正常及ALT异常肝穿病理证实存在肝硬化患者肝功能、性别、HBeAg、HBV-DNA及组织病理学结果,应用秩和检验、χ2检验及Spearman相关分析进行统计分析.结果 ALT正常组与ALT异常各组比较,肝脏组织病理炎性程度无明显差异,ALT正常组HBV DNA载量较ALT异常组低,AST/ALT比值大于1与ALT异常组比较存在明显差异,血清白蛋白、性别、HBeAg及胆碱脂酶在各组之间差异无统计学意义;在ALT正常亚组中,72%的患者ALT在30～50 U/L之间,两组之间组织病理差异无统计学意义;在所有的肝硬化患者中,HBeAg定量与肝脏炎性程度无相关性,与HBV DNA载量呈正相关.结论 ALT正常乙型肝炎肝硬化患者肝脏组织存在明显炎症,AST/ALT比值大于1在肝硬化组明显升高,炎性程度各组之间无明显差异,HBeAg定量与肝脏炎性程度无相关性,而与HBV DNA载量呈正相关.     

慢性乙型肝炎、乙肝肝硬化、乙肝肝癌患者Th1/Th2型细胞因子水平变化研究

目的分析慢性乙型肝炎(CHB)、乙肝肝硬化(LC)、乙肝肝癌(HCC)患者血清中Th1/Th2型细胞因子水平变化,为慢性乙型肝炎至肝癌的发生发展过程中的免疫变化研究提供线索,并为患者的临床治疗研究提供免疫学指标。方法选取2010年2月-2011年11月于首都医科大学附属北京佑安医院就诊的40例CHB患者、40例LC患者、53例HCC患者,用Luminex技术检测血清中Th1类细胞因子[白细胞介素(interleukin,IL)-12、干扰素(interferon,IFN)-γ和肿瘤坏死因子(tumor necrosis factor,TNF)-α]水平及Th2类细胞因子(IL-4、IL-6和IL-10)水平,并将25例健康志愿者作为正常对照组进行比较。结果除TNF-α外,CHB组、LC组和HCC组Th1类IL-12、IFN-γ和Th2类IL-4、IL-6、IL-10细胞因子水平均低于正常对照组;CHB组中大部分Th1类和Th2类细胞因子都高于LC组和HCC组;HCC组中TNF-α细胞因子水平要高于CHB组、LC组。结论 CHB、LC和HCC患者体内Th1/Th2细胞因子分泌水平受到抑制,Th1/Th2平衡发生漂移,对HBV病毒的清除作用受到抑制。TNF-α在肝癌发生过程中发挥着重要作用。     

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.
METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.
RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.
CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA mor     

拉米夫定治疗活动性肝炎肝硬化的疗效观察

目的 观察活动性肝炎肝硬化患者拉米夫定长程治疗的疗效及对停药后肝功能异常的对策探讨。 方法口服拉米夫定100 mg,每日一次,连服18个月治疗活动性肝炎肝硬化患者58例。观察治疗前后的临床症状体征、生化指标、病毒学改变情况、停药后情况及对策探讨。 结果 (1)35例(74.5％)患者治疗后病情缓解稳定,生活质量改善,child-pugh积分下降;肝功恢复正常或好转。(2)HBV DNA下降>10~3拷贝/ml;HBeAg阴转率达33.3％(13/39)。(3)10例停药后,在3-6个月随访期间肝炎复发再次住院。停药后肝功能异常的治疗:2例用干扰素治疗1个月后出现黄疸、肝损害加重,立即停药保肝处理后缓解;8例患者未加任何抗病毒药物,经加强保肝、调节免疫等治疗后,肝功能得到改善。 结论 乙型肝炎后肝硬化患者伴有活动性病毒复制及肝炎时,长程拉米夫定治疗可改善肝功能,阻止病情进展,提高生活质量;停拉米夫定后肝炎活动不宜应用干扰素治疗。     

Successful treatment with lamivudine may correlate with reduction of serum ferritin levels in the patients with chronic hepatitis and liver cirrhosis type B

Purpose  To study the changes in serum ferritin levels in lamivudine (LAM)-treated patients with chronic hepatitis and liver cirrhosis type B and determine whether successful treatment with LAM results in a reduction of serum ferritin levels. Methods  Thirty patients with chronic hepatitis B virus (HBV) infection were followed prospectively during their treatment with LAM for 12 months. Serum HBV DNA, ferritin levels, and emergence of YMDD mutants were monitored. A case of severe liver cirrhosis with hepatic hemosiderosis that was treated successfully with LAM also is shown as a representative case. Results  Serum alanine aminotransferase and ferritin levels decreased significantly more in the patients treated with LAM without YMDD mutants (n = 23) than those with mutants (n = 7). Hepatic hemosiderosis along with serum iron markers improved greatly in the representative patient. Conclusion  Successful treatment with LAM may reduce serum ferritin levels and improve hepatic siderosis in a subset of patients with chronic HBV infection. A study of Niigata-Zeffix investigation meeting.     

Prediction of chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma by SELDI-based serum decision tree classification

PURPOSE: To screen potential serological biomarkers and develop decision tree classifications of chronic hepatitis B, liver cirrhosis (LC) and hepatocellular carcinoma (HCC), respectively, with high prediction score for improving diagnosis of liver diseases. METHODS: The total serum samples were randomly divided into three training sets (41 HBV and 35 health; 36 LC and 35 health; 39 HCC and 35 health) and three testing groups (34 HBV and 38 health; 18 LC and 52 health; 42 HCC and 47 health). Selected WCX2 protein chip capture followed by SELDI-TOF-MS analysis was applied to generate the serum protein profiles. Subsequently serum protein spectra were normalized and aligned by Ciphergen SELDI Software 3.1.1 with Biomarker Wizard including baseline subtraction, mass accuracy calibration, automatic peak detection. Once the intensities of selected significant peaks from the training data set were transferred to further BPS analysis, an optimized classification tree with sequence-decision was established to divide training data set into disease group and control group successfully. A double blind test was employed to determine the clinical sensitivity and clinical specificity of three models. RESULTS: After comparative analysis of SELDI based serum protein profile between the cases of disease and healthy, a HCC decision tree classification with sensitivity of 94.872% and specificity of 94.286%; a LC decision tree classification with sensitivity of 91.667% and specificity of 94.286% and a HBV decision tree classification with sensitivity of 95.122% and specificity of 94.286% were produced by BPS respectively. When three decision tree models were challenged by the double-blind test samples, clinical sensitivity and clinical specificity of these models were predicted in diagnosis of three liver diseases (HCC: 90.48 and 89.36%; cirrhosis: 100 and 86.5%; HBV: 85.29 and 84.21%). CONCLUSION: SELDI-based decision tree classifications showed great advantages over conventional serological biomarkers in the diagnosis of chronic hepatitis B, LC as well as HCC.