乙型重型肝炎患者血清HMGB1表达水平及其与肝生化指标相关性的研究

目的分析乙型重型肝炎患者血清高迁移率族蛋白1(HMGB1)表达水平及其与肝生化指标的相关性。方法将2015年7月至2016年12月期间我院收治的60例乙型重型肝炎患者(重型组)和60例慢性乙型肝炎患者(慢性组)以及门诊体检无异常的60名健康者(健康组)为研究资料。分析3组患者血清HMGB1水平差异和肝生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)、凝血酶原活动度(PTA)及白蛋白(Alb)水平差异,再将60例乙型重型肝炎患者血清HMGB1水平与肝生化指标ALT、AST、TBil、PTA及Alb进行Pearson相关性分析,以得出血清HMGB1水平与肝生化指标ALT、AST、TBil、PTA及Alb的相关性。结果健康组血清HMGB1水平低于慢性组,慢性组低于重型组(P0.05)。健康组血清ALT、AST、TBil水平均低于慢性组,慢性组低于重型组(均P0.05)。乙型重型肝炎患者血清HMGB1水平和ALT、AST、TBil水平均为正相关(均P0.05),和PTA、Alb水平均为负相关(均P0.05)。结论肝功能损伤越重,患者血清HMGB1水平越高。     

miR-375、miR-146a及miR-21在慢性乙型病毒性肝炎、肝硬化及肝癌患者中表达及其对肝癌的诊断意义

目的观察慢性乙型病毒性肝炎(简称乙肝)、肝硬化及肝癌患者血清中乙型肝炎病毒(HBV)-DNA、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)和碱性磷酸酶(ALP)水平,并分析miR-375、miR-146a及miR-21在3组中的表达变化。方法收集43例慢性乙肝患者纳入慢性乙肝组、36例肝硬化患者纳入肝硬化组,31例肝癌患者纳入肝癌组。采用全自动生化分析仪检测血清中ALT、AST、GGT和ALP水平;采用荧光定量聚合酶链式反应(PCR)检测3组血清中HBV-DNA的浓度及miR-375、miR-146a和miR-21的表达情况,并用受试者工作特征(ROC)曲线进行分析。结果肝硬化组HBV-DNA阳性率明显低于慢性乙肝组和肝癌;3组血清ALT、AST、GGT和ALP水平有明显差异(P0.05);肝癌组血清ALT、AST水平明显低于慢性乙肝患者,血清ALP水平明显高于慢性乙肝组。miR-146a及miR-21在慢性乙肝、肝硬化及肝癌患者血清中的水平呈现显著增高趋势,miR-375表达则呈现显著下调趋势(P0.05);miR-375、miR-146a及miR-21者联合检测对肝癌诊断的灵敏度、特异度和准确度较单独检测明显提升。结论血清HBV-DNA和血清酶学检测对于慢性乙肝患者疾病进展的判断有一定辅助作用;联合检测miR-375、miR-146a及miR-21可提高对肝癌的诊断效能。     

肝病患者血清铁蛋白水平与肝脏炎症程度及肝病类型的关系

目的分析血清铁蛋白(SF)水平与肝病类型及肝脏炎症程度的关系。方法选取203例入院时SF升高的急慢性肝病患者,采用全自动生化分析仪检测患者清晨空腹血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、白蛋白(ALB),同时采用免疫比浊法检测SF、络合法测定血清铁(SI),分析SF、SI与肝功能炎症指标相关性,及SF、SI在不同类型肝病、不同程度肝脏炎症患者中的变化特点。结果 SF、SI与ALT、AST均呈正相关(P均<0.01),SF与ALB呈负相关(P<0.01)。SF水平在戊型肝炎、药物性肝炎、乙型肝炎、丙型肝炎患者中依次升高(χ2=13.551,P<0.01),ALT、AST的升高程度同SF一致;SI在不同类型肝病患者之间的差异无统计学意义(P>0.05)。SF在急性肝炎与肝衰竭中的升高水平较慢性肝炎、肝硬化、肝癌患者明显;SI在肝癌患者表达量最低,其余四组之间的差异无统计学意义(P>0.05)。结论 SF与肝脏炎症程度正相关,在丙肝及肝衰竭患者中,SF比ALT、AST更能反映患者的病情。     

血清生化指标对慢性肝炎病变程度的评价

目的:分析临床肝病常用血清生化指标与慢性肝炎病变程度的相关性.方法:检测慢性肝炎患者142例的丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、谷氨酰转肽酶(GGT)、白蛋白(ALB)、总胆红素(TBIL)和凝血酶原活动度(PTA),并将其结果与肝炎病变程度(病理分级和分期)对比分析.结果:ALT、AST、ALB和PTA在不同病理分级(炎症)之间均有显著性差异( F = 6.812,6.592,10.131,3.247,P<0.05或0.01); ALT、AST、ALP、GGT、ALB、TBIL和PTA在不同病理分期(纤维化)之间无显著性差异;TBIL、PTA和病理分级呈正相关,ALB和病理分级分期呈负相关.结论:常用血清生化指标ALT、AST、ALB、PTA能反映慢性肝炎的炎症程度,但不能反映慢性肝炎的纤维化程度.     

血清可溶性IL-2受体测定在急慢性肝脏疾病中的意义

目的 探讨急慢性肝病可溶性白介素2受体的改变,为诊断病情演变和预后判定寻找可靠的依据。 方法 健康对照(n=30)研究,采用夹心酶联免疫吸附法测定173例各型肝病患者血清IL-2受体(sIL-2R)水平,包括急性病毒性肝炎80例,慢性乙型肝炎21例,肝炎后肝硬化35例和原发性肝癌37例,并对测定结果进行分析。 结果 各组患者血清sIL-2R均明显高于对照组(P<0.01),其中急性病毒性肝炎黄疸期血清sIL-2R明显高于恢复期(P<0.01),各型急性肝炎之间血清sIL-2R无显著差异(P>0.05);急性肝炎组明显高于慢性肝炎组(P<0.01);慢性乙型肝炎ALT异常组血清sIL-2R明显高于ALT正常组(P<0.01);Child's C级肝炎后肝硬化者明显高于CHild'B,A级者(P<0.01);原发性肝癌者血清sIL-2R水平与肿瘤体积大小有关(P<0.05)。 结论 急慢性肝病患者血清sIL-2R水平均明显增高,其水平的高低在一定程度上反映了机体免疫功能状态和肝细胞损伤的程度。     

乙肝患者体内HBV复制与肝损伤的相关性探讨

目的 探讨乙型肝炎(乙肝)患者体内病毒复制与肝损伤的关系.方法 取400份住院乙肝患者血清,测定HBV-DNA水平、乙肝病毒血清标志物(HBV-M)及肝功指标ALT及AST.分析各指标间的相关性.结果 HBeAg 阳性患者HBV-DNA水平明显高于HBeAg 阴性患者,P＜0.05;二者的HBV-DNA水平与ALT及AST均无显著差异;大三阳与小三阳患者HBV-DNA水平与ALT及AST亦均无显著性差异.结论 乙肝患者 HBV-DNA水平与肝损伤程度无明显相关性.     

冠心病患者血清γ-谷氨酰转移酶水平变化及临床意义

目的 研究冠心病患者血清γ-谷氨酰转移酶（GGT）与冠心病严重程度及主要危险因素的关系。方法 对笔者医院888例冠心病患者行冠状动脉造影、超声检查,并检测血清GGT、丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平。结果 与GGT正常组相比,GGT升高组ALT、AST增加,TG上升,HDL-C下降,LVEF下降,Gensini评分升高。且GGT与ALT、AST、TC、TG、LDL-C和Gensini评分呈正相关,与LVEF和HDL-C呈负相关。结论 冠心病患者血清GGT水平与冠心病严重程度及冠心病的主要危险因素有关。     

慢性乙型重型肝炎患者血清sICAM-1的检测及临床意义

目的探讨慢性乙型重型肝炎患者血清可溶性细胞间粘附分子-1(sICAM-1)的变化及其临床意义。方法采用双抗体夹心酶联免疫吸附法对50例慢性乙型重型肝炎患者和30例正常人血清sICAM-1水平进行测定。对50例慢性乙型重型肝炎患者用ELISA法检测乙型肝炎病毒血清标志物,荧光定量PCR法检测HBV DNA载量、全自动生化分析仪检测肝功能、全自动血凝分析仪检测凝血酶原活动度(PTA)。结果慢性乙型重型肝炎患者血清sICAM-1水平明显高于健康对照组(P<0.01),存活组血清sICAM-1水平明显高于死亡组(P<0.01);慢性乙型重型肝炎患者血清sI-CAM-1水平与PTA呈显著正相关(r=0.475,P<0.01),与血清总胆红素呈显著负相关(r=-0.395,P<0.01),与丙氨酸氨基转移酶、白蛋白无相关性(r=0.014、-0.214,P>0.05);27例HBV DNA<1×105copies/ml者与23例HBV DNA≥1×105copies/ml者血清sICAM-1水平无显著性差异(P>0.05);7例HBeAg( )/HBeAb(-)者与43例HBeAg(-)/HBeAb( )者血清sICAM-1水平也无显著性差异(P>0.05)。结论慢性乙型重型肝炎患者血清sI-CAM-1水平显著高于健康对照组,存活组血清sICAM-1水平明显高于死亡组。sICAM-1参与了慢性乙型重型肝炎的肝损伤过程,并与患者病情程度有一定的相关性,但与乙型肝炎病毒的复制水平无相关。     

乙肝患者血清IL-2、sIL-2R水平与肝损程度、HBV DNA含量的变化

目的 探讨乙型肝炎患者血清IL-2、sIL-2R含量与肝损程度和HBV DNA含量的相关性及临床意义.方法 收集急、慢、重型乙肝患者血清标本共93例,28例健康人血清标本作为对照组,采用ELISA法检测各型乙型肝炎患者血清中IL-2、sIL-2R.HBV DNA定量采用荧光定量PCR法.结果 各型乙肝患者血清中IL-2均有所下降,sIL-2R均高于正常对照组(P＜0.05),并随肝损伤程度加重,含量随之增加.慢性肝炎患者血清sIL-2R水平与HBV DNA含量呈正相关系.结论乙型肝炎患者血清IL-2、sIL-2R水平及HBV DNA含量可作为判断感染乙肝病毒后机体免疫水平和细胞受损程度的参考指标.     

前列腺素E2促进乙型肝炎病毒复制的机制研究

目的探讨前列腺素E2(PGE2)对乙型肝炎病毒(HBV)复制及T细胞功能的影响。方法ELISA法检测慢性乙肝患者(CHB,120例)和健康体检者(HP,60例)血清中PGE2的浓度。检测PGE2高水平或低水平患者血清中丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)的水平,流式细胞术检测血样中CD8+T细胞功能相关指标。将24只经尾静脉注射重组病毒rAAV8-1.3HBV的小鼠随机均分为3组,每组8只:对照组(DMSO)、PGE2组(PGE2的稳定类似物)和PGE2受体拮抗组(PGE2受体拮抗剂),试剂盒及实时定量PCR检测3组小鼠血清中HBsAg、HBV DNA及pgRNA水平,流式细胞术检测肝脏中CD8+T细胞功能相关指标。结果与HP(201.3±13.38)对比,CHB患者(877.2±43.27)血清中PGE2水平显著增加(P<0.05)。与PGE2低水平患者相比,PGE2高水平患者血清中HBV DNA(1.84±0.161)、ALT(722.64±33.081)、AST(514.20±13.427)水平显著增加,CD8+T细胞中Tim3的表达显著增加(18.64±2.051),颗粒酶B的表达显著降低(0.29±0.102)(P<0.05)。与对照组相比,PGE2组小鼠血清中HBsAg(5.57±0.941)、HBV DNA(0.58±0.073)及pgRNA(0.57±0.069)水平显著增加,肝脏CD8+T细胞中Tim3(25.45±3.412)的表达显著增加,TNF-α(21.50±3.139)和IFNγ(15.23±2.105)的表达显著降低(P<0.05)。PGE2受体拮抗有相反的效果。结论PGE2在CHB患者血清中呈高表达,PGE2促进HBV复制及T细胞衰竭,PGE2信号阻断不仅可修复T细胞功能还可控制HBV复制。     

Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis

To analyze interleukin-2-dependent immunoregulatory function in hepatitis B virus infection and in other forms of viral hepatitis, levels of soluble interleukin-2 receptors (sIL-2R) were measured by an enzyme-linked assay in sera from patients with acute and chronic viral hepatitis of different etiology. Increased sIL-2R levels were detected in the early phase of acute hepatitis type A and type B, but not during acute non-A, non-B hepatitis. Among 46 patients with chronic hepatitis B virus infection, levels of sIL-2R were significantly increased only in cases with chronic active hepatitis, while they were about normal in chronic persistent hepatitis or in healthy carriers of the infection. These differences were independent of virus replication, being maintained when patients were stratified according to HB_eAg/anti-HB_e status and to serum HBV-DNA. Nine patients with chronic active hepatitis type B and high sIL-2R levels at presentation were followed prospectively for two to eight years, and in HB_eAg -positive patients, the behavior of receptor levels closely paralleled disease activity. These results, which may reflect increased shedding of IL-2R by activated T lymphocytes in patients with active destruction of HBV infected hepatocytes, indicate the usefulness and potential prognostic importance of serum slL-2R determination in patients with chronic viral hepatitis. Patients with chronic non-A, non-B hepatitis had much lower sIL-2R levels, although their liver disease was similar to hepatitis B cases, suggesting that different pathogenetic mechanisms operate in these patients.     

Serum Soluble Interleukin-2 Receptor Levels Before and During Interferon Treatment in Patients with Chronic Hepatitis B Virus Infection

To determine the role of serum solubleinterleukin-2 receptor (sIL-2R) in chronic hepatitis Bvirus (HBV) infection, the level of serum sIL-2R wasmeasured in sera of 105 patients with chronic HBVinfection and in 21 healthy controls, using enzyme-linkedimmunosorbent assay. Serum sIL-2R levels weresignificantly higher in chronic HBV-infected patientswith chronic hepatitis (508 ± 310 units/ml) andliver cirrhosis (543 ± 283 units/ml) than inhealthy controls (331 ± 106 units/ml, P <0.05). Moreover, serum sIL-2R levels were significantlyhigher in patients with chronic hepatitis or livercirrhosis than in asymptomatic HBV carriers (341 ±150 units/ml, P < 0.01). There was no difference inserum sIL-2R levels between asymptomatic HBV carriersand healthy controls or between patients with chronic hepatitis and liver cirrhosis. A significantrelationship was found between serum sIL-2R and ALTlevels (P < 0.05) in patients with chronic HBVinfection, although there was no correlation betweensIL-2R and HBV DNA levels. Serum sIL-2R levels in mostpatients decreased to the same level as asymptomatic HBVcarriers and healthy controls at 48 weeks after the endof treatment, and serum ALT and HBV DNA levels were decreased to within the normal range at 96weeks. Thus, serum sIL-2R levels indicate the degree ofliver damage among patients with chronic HBV infection.The serum sIL-2R levels one year after interferon administration may be a useful marker ofdetermined at the effectiveness by thistreatment.     

老年病毒性肝炎和肝细胞癌患者外周血可溶性白细胞介素2受体的检测及意义

应用单克隆抗体夹心酶联免疫吸附试验(ELISA)对75例老年病毒性肝炎和肝细胞癌患者血清的可溶性白细胞介素2受体(sIL-2R)进行检测,并与健康老年人作对照比较。结果显示,急性肝炎黄疸期、慢性肝炎(中度)、重型肝炎组血清sIL-2R分别为129.36±37.15/ml、174.44±91.90u/ml、245.00±77.67u/ml,明显高于正常对照组的72.67±43.46/ml(P<0.01)。而慢性肝炎(轻度)、急性肝炎恢复期、肝癌组分别为82.67±30.86u/ml、73.61±20.28u/ml、70.12±30.36u/ml,与正常对照组比较无显著差异(P>0.05)。sIL-2R水平与感染的肝炎病毒类型无关(P>0.05)。老年肝癌组经免疫增强型治疗后血清sIL-2R水平升高至207.14±88.45u/ml(P<0.05)。血清sIL-2R含量的消长与疾病严重程度似呈正相关,提示临床检测sIL-2R水平对判定病情变化和预后及评估机体免疫状态有一定的意义。老年人免疫力低下可能是肝癌的重要致病因素之一。     

Serum soluble interleukin-2 receptor levels in patients with chronic hepatitis B virus infection and its relation with anti-HBc

AIM:To investigate the relationship between serumsoluble interleukin-2 receptor(sIL-2R)level and anti-HBcin patients with chronic hepatitis B virus(HBV)infection.METHODS:Sera from 100 patients with chronic HBVinfection and 30 healthy controls were included in thisstudy.The patients were divided into group A[HBsAg( ),HBeAg( )and anti-HBc( ),n=50]and group B[HBsAg( ),HBeAg( )and anti-HBc(-),n=50].sIL-2R levelswere determined using ELISA.HBV DNA and alanineaminotransferase(ALT)were also detected.RESULTS:Serum sIL-2R levels were significantly higherin patients with chronic HBV infection than in healthycontrols.Moreover,serum sIL-2R levels were significantlyhigher in patients with HBsAg( ),HBeAg( )and anti-HBc( )(976.56±213.51×10~3 U/L)than in patients withHBsAg( ),HBeAg( )and anti-HBc(-)(393.41±189.54×10~3 U/L,P<0.01).A significant relationship was foundbetween serum sIL-2R and ALT levels(P<0.01)inpatients with chronic HBV infection,but there was nocorrelation between sIL-2R and HBV DNA levels.Theanti-HBc status was significantly related to the age ofpatients(P<0.01).CONCLUSION:The high sIL-2R level is related topositive anti-HBc in chronic hepatitis B patients.Positiveanti-HBc may be related to T-lymphocyte activation andnegative anti-HBc may imply immune tolerance in thesepatients.     

可溶性白介素2受体在慢性乙型肝炎中的意义及其升高机制初探

用夹心酶联免疫吸附法检测了３９例慢性乙型肝炎病人血清可溶性白介素２受体（ｓＩＬ－２Ｒ）水平以及病人外周血淋巴细胞（ＰＢＬ）在体外经植物血凝素（ＰＨＡ）刺激后ｓＩＬ－２Ｒ的分泌能力。结果示慢性乙型肝炎病人血清ｓＩＬ－２Ｒ明显高于对照组，并且其升高与病人血清谷丙转氨酶（ＡＬＴ）及肝内单个核细胞浸润和肝细胞坏死相关。而病人ＰＢＬ经ＰＨＡ刺激分泌ｓＩＬ－２Ｒ的能力与正常人无明显差异。     

各型乙型肝炎患者血清sIL-2R、IFN-γ和IL-l变化的研究

目的:探讨各型乙型肝炎患者血清sIL-2R、IFN-γ和IL-l变化及其临床意义。方法:收集急性肝炎、慢性肝炎、慢性重型肝炙和活动性肝硬变患者血清标本各16份,16例健康人血清标本作为正常对照组,采用酶联免疫吸附试验(ELISA)检测各型乙型肝炎患者血清中sIL-2R和IFN-γ水平,采用MTT法检测各型乙型肝炎患者血清中IL-1水平,并与正常对照组进行比较。结果:急性肝炎患者血清sIL-2R、IFN-γ和IL-1水平均明显升高(P<0.01);慢性肝炎患者血清sIL-2R水平升高(P<0.05),IFN-γ水平无明显变化,IL-1水平稍降低;慢性重型肝炎患者血清sIL-2R和IFN-γ水平升高(P<0.05 and P<0.01 respectiveIy).但IL-1水平降低;活动性肝硬变患者血清sIL-2R和IFN-γ水平明显升高(P<0.01),但IL-1水平无明显变化。结论:血清sIL-2R、IFN-γ和IL-1参与各型乙型肝炎的发病机制,调整血清中细胞因子含量可能有助于乙型肝炎的治疗。     

Effects of α-Interferon and Prednisone on Serum-Soluble Interleukin-2 Receptor (sIL-2R) in Chronic Hepatitis B Infection

The level of serum-soluble interleukin-2 receptor (sIL-2R) was measured in 32 patients to investigate the effect of prednisone and alpha-interferon therapy on chronic hepatitis B virus infection. All the patients were seropositive for hepatitis B surface antigen and hepatitis B e antigen, with histological evidence of chronic persistent or chronic active hepatitis. Twenty-six patients received oral prednisone, followed by subcutaneous recombinant alpha-interferon, and six patients received multivitamin tablets and served as controls. After 4 wk of prednisone in reducing dosage, serum sIL-2R fell significantly from 673.6 +/- 52.9 U/ml to 584.8 +/- 39.4 U/ml (mean +/- SE, p less than 0.05). It rose to 733.4 +/- 45.7 U/ml (p less than 0.05) on the 4th wk of interferon, but returned to pretreatment level at completion of interferon. There was a significant correlation between serum sIL-2R and alanine aminotransferase levels (r = 0.36, p less than 0.001). The level of serum sIL-2R before treatment and its response to prednisone and interferon were not useful in predicting seroconversion of hepatitis B e antigen and anti-hepatitis B e.     

和解汤对慢性乙型肝炎患者HBeAg阴转后阴转状态的影响

探讨和解汤对慢性乙型肝炎HBeAg阴转后阴转状态的影响。方法将慢性乙型肝炎HBeAg阴转但SIL-2R水平仍高的患者41例随机分为两组,治疗组26例采用和解汤治疗;对照组15例予以常规西药护肝治疗。均于治疗3个月后抽取患者外周血检查SIL-2R水平。结果治疗组SIL-2R水平下降(P＜0.05),且HBeAg重新阳转者1例;对照组SIL-2R水平无明显变化(P＞0.05),且HBeAg重新阳转者4例,与治疗组比较差异有显著性意义。结论HBeAg阴转但SIL-2R水平仍高的患者,HBeAg阴转可能是暂时现象,应继续予以有效治疗,和解汤对保持HBeAg阴转状况有一定疗效。     

Serum levels of soluble interleukin-2 receptors and effects of interferon-α for patients with chronic hepatitis C virus

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-. The sIL-2R levels of 40 asymptomatic HCV carriers (632±340 units/ml), 47 patients with chronic hepatitis (547±204 units/ml), 10 with cirrhosis (679±239 units/ml), and 20 with hepatocellular carcinoma (1145±487 units/ml) were significantly higher than those of healthy controls (380±191 units/ml) (P<0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r=0.348,P<0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients in whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.