慢性乙肝患者血清趋化因子RANTES水平与肝功能生化指标等的相关性研究

目的 了解慢性乙型肝炎(慢性乙肝)患者血清趋化因子RANTES水平,探讨血清RANTES水平与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)、凝血酶原活动度(PTA)、乙型肝炎e抗原(HBeAg)及乙型肝炎病毒(HBV DNA)载量的相关性.方法 选择144例慢性乙肝患者(观察组)和18名健康人(对照组),采取静脉血并应用ABC-ELISA方法 检测其血清中趋化因子RANTES浓度,并与两组的肝功能检测生化指标、HBeAg和HBV DNA载量进行相关性分析,利用SPSS13.0软件进行统计分析.结果 慢性乙肝患者血清RANTES的浓度比正常对照组升高,血清RANTES浓度分别为(3930.12±2856.96)ng/ml和(329.46±152.23)ng/ml,两组之间差异比较均有统计学意义(P<0.05);RANTES水平与ALT(r=0.197,P:0.018)、AST(r=0.239,P=0.004)和Tnil(r=0.316,P=0.001)呈显著正相关;RANTES水平与PTA(r=-0.078,P=0.357)无显著相关;HBeAg阴性组与HBeAg阳性RANTES水平比较无统计学意义(P=0.407);HBV DNA低载量组(<105拷贝/ml)和HBVDNA高载量组(≥105拷贝/ml)RANTES水平比较无统计学意义(P=0.185).结论 慢性乙肝患者血清中RANTES表达水平增高,血清RANTES水平与ALT、AST和TBIL呈正相关,与PTA无相关性.RANTES水平可反映肝脏炎症活动及损害情况,不受HBeAg、HBV DNA载量影响,可能参与慢性乙肝发病.     

慢性乙肝患儿HBV基因型与乙肝病毒大蛋白关系探讨

目的 探讨慢性乙型肝炎患儿HBV基因型与乙肝病毒大蛋白的关系.方法 采用实时荧光PCR法和ELISA法分别检测138例处于乙肝病毒活动期的慢性乙型肝炎患儿血清中的HBV DNA和乙肝病毒大蛋白并鉴定其基因型.结果 乙肝病毒大蛋白吸光度与HBV DNA载量存在正相关（r=0.85,P＜0.05）;HBV基因B型与HBV基因C型的ALT水平、乙肝病毒大蛋白吸光度和HBVDNA载量差异无统计学意义（P＞0.05,P＞0.05,P＞0.05）.结论 乙肝病毒大蛋白水平与HBVDNA载量具有良好的正相关性,表明乙肝病毒活动期的慢性乙肝患者体内乙肝病毒大蛋白与病毒复制程度密切相关,乙肝病毒基因型与乙肝病毒大蛋白无关.     

慢性重型乙型肝炎患者血清IL-23水平检测及其意义

目的 检测慢性重型乙型肝炎患者血清中IL-23表达,探讨IL-23水平与丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(TBil)及HBV DNA载量的相关性.方法 用酶联免疫吸附法(ELISA)检测50例慢性重型乙型肝炎患者(重肝组)及18名健康人(对照组)血清中IL-23表达,并与患者ALT、AST、TBil、HBV DNA载量进行相关性分析.结果 重肝组患者血清中IL-23表达高于对照组,两组之间的差异有统计学意义(P＜0.05);IL-23水平与ALT、AST呈正相关(P＜0.05),与TBil、HBV DNA载量无相关性(P＞0.05).结论 慢性重型乙型肝炎患者血清中IL-23表达增高,与炎症程度相关,可能参与慢性重型乙型肝炎的发病.     

高灵敏度乙肝核酸定量与乙肝血清标志物的相关性分析

目的 探讨高灵敏度的荧光定量PCR检测的乙型肝炎病毒核酸(HBV DNA)与乙肝血清免疫标志物(HBV M)之间的相关性及临床意义.方法 选取234例患者标本,同时检测HBV DNA载量和HBV M.根据HBV M模式将结果分为五组,并对HBV DNA载量和HBV M之间的关系进行分析.选取177例乙肝患者,分析HBV DNA载量水平与HBeAg之间的关系.结果 Ⅰ组HBV DNA阳性率为77.4％;Ⅱ组HBV DNA阳性率为70.4％,两者之间差异无统计学意义(χ2=0.617,P ＞0.05).HBeAg表达水平与HBV DNA载量之间存在正相关关系(γ=0.812,P＜0.01).结论 高灵敏度HBVDNA与经典化学发光法的检测结果之间有很好的相关性.提高HBV DNA的检测灵敏度对于乙型肝炎患者,尤其对小三阳患者的病情和疗效评估具有重要的临床意义.     

失代偿期乙肝肝硬化患者血清HBV DNA水平与临床特征及48周短期转归关系

目的 观察失代偿期乙肝肝硬化患者血清HBV DNA载量水平与临床特征及48周临床转归的关系.方法 143例患者Child-Pugh评分、基础情况相当,分为低病毒载量组46例和高病毒载量97例.两组病例均给予常规对症支持治疗,低病毒载量组21例、高病毒载量组52例,在常规治疗基础上根据患者的经济情况及意愿给予核苷类似物抗病毒治疗.结果 观察前两组患者人口学及基线ALT、ALB、TBil、CHE等方面比较,差异均无统计学意义(P>0.05),在AST、HBeAg阳性率方面比较,差异均有统计学意义(P<0.05).低病毒载量组与高病毒载量组比较,48周血清AST、ALT、TBiL、ALB、CHE差异均无统计学意义(P>0.05).两组死亡率相近,而低病毒载量组原发性肝癌、自发性腹膜炎及消化道出血等均高于高病毒载量组.结论 失代偿期乙肝肝硬化患者病情并不随着病毒载量的下降而缓解,低病毒载量患者也应当重视早期治疗.     

乙型肝炎病毒基因型和DNA载量与外膜大蛋白关系研究

目的 探讨乙型肝炎病毒基因型和DNA载量与外膜大蛋白关系.方法 采用荧光定量PCR方法 ,ELISA法和时间分辨免疫荧光分析法分别检测140例慢性乙型肝炎患者血清中HBVDNA、LHBs(Hepatitis B Virus Large Envelope Protein,LHBs)和HBV血清标志物,对HBV DNA阳性标本进行基因测序鉴定基因型,并进行相关性分析.结果 HBV LHBs与HBV DNA阳性率在HBcAg阴性和阳性组中差异均无统计学意义(P＞0.05);HBV LHBs吸光度A值与HBV DNA载量存在良好的相关性,相关系数为0.9267;乙型肝炎病毒B、C基因型间HBV-LHBs吸光度A值差异无统计学意义(P＞0.05).结论 血清LHBs水平与HBV DNA载量存在良好的相关性,能反映HBV感染者体内HBV复制程度,可作为判断HBV复制新的血清学指标;HBV LHBs的含量与HBV基因型无关.     

慢性乙型肝炎患者e抗原消失的临床特点

目的 探讨慢性乙型肝炎患者使用核苷类似物抗病毒治疗e抗原消失后HBV DNA、转氨酶等指标的变化特点。方法 选取2014年12月~2017年6月四川省中西医结合医院门诊109例慢性乙型肝炎患者,在服用核苷类似物抗病毒的治疗过程中出现e抗原消失,检测并分析治疗前后e抗原抗体系统的变化与HBV DNA关系、ALT异常率、血清HBV DNA水平与HBeAg相关性分析。结果 HBV DNA转小二阳时及转后半年、1年与治疗前比较,差异有统计学意义（P＜0.05）;转小二阳后半年与刚转小二阳时比较,差异有统计学意义（P＜0.05）;转小二阳后1年与刚转小二阳时比较,差异无统计学意义（P＞0.05）。治疗前和治疗后的ALT异常率比较,差异有统计学意义（P＜0.05）,转小二阳时以及转后的半年、1年ALT异常率相比,差异均无统计学意义（P＞0.05）。血清HBV DNA水平与HBeAg呈正相关关系（r=0.879,P＜0.001）。结论 大三阳患者在治疗过程中,发生e抗原的消失的状态是不稳定的,仍然可能会出现病毒DNA的复制,转氨酶的异常。     

HBV感染不同病程中病毒载量与肝功能相关指标及免疫功能的变化分析

目的 探讨HBV感染者外周血肝功能主要指标、T细胞亚群以及病毒载量在不同病程中的变化及其临床意义.方法 170例HBV感染患者根据病程分成急性乙肝组(18例)、慢性乙肝组(73例)、肝硬化组(41例)及肝癌组(38例),正常对照组40例.用全自动生化分析仪和流式细胞仪检测各组肝功能相关指标及T细胞亚群含量;采用实时荧光定量PCR法检测HBV-DNA含量.结果 四组实验组与正常对照相比谷丙转氨酶(ALT)、谷草转氨酶(AST)均升高,差异具有统计学意义(P＜0.05),且以急性乙肝升高最为显著,慢性乙肝次之,组间比较可见慢性乙肝患者组比急性乙肝患者组ALT、AST有所下降,且差异具有统计学意义(P＜0.05),而肝癌患者组和肝硬化组之间则变化不显著,差异无统计学意义(P＞0.05);碱性磷酸酶ALP的升高见于肝癌患者组,慢性乙肝患者组ALP水平较低;各组总蛋白(TP)均在正常参考范围内.四组实验组外周血CD3+T细胞均比正常对照组低,其中肝癌组、肝硬化患者组降低最为明显,CD4+T细胞比例上升见于急性乙肝组,而CD8+T细胞的比例在急性乙肝患者组中最低.外周血中HBV病毒核酸载量升高的最为明显的是慢性乙肝患者组,而急性乙肝患者组、肝硬化患者组、肝癌患者组的HBV-DNA水平比较低,以急性乙肝最低,各组与其相比均具有统计学差异(P＜0.05).结论 HBV不同病程中患者的肝功能相应指标、T细胞亚群表达、HBV-DNA含量存在显著差异,联合检测这些项目可为临床正确评估患者的病情及病程提供相应指导,为疾病转归的判断及治疗提供可靠的依据.     

HBeAg阴性与阳性慢性乙肝患者的临床对比分析

目的 探讨HBeAg阳性和HBeAg阴性慢性乙肝患者的临床特征异同.方法 随机选取慢性乙肝患者354例,其中HBeAg阳性组124例,HBeAg阴性组230例,对两组的人口学、生化学、病毒学及诊断分型进行分析比较.结果 ①与HBeAg阳性组比较,HBeAg阴性组患者年龄较大(P=0.000),中度和重度慢性肝炎比例较低(P:0.007和0.014),重型肝炎发生率较高(P=0.008).②HBeAg阴性组的ALT、ALB、PTA及HBV DNA载量对数值低于HBeAg阳性组(P=0.035,0.002,0.000和0.000),但TBil水平高于HBeAg阳性组(P=0.003);两组AST水平差异无统计学意义(P=0.222).③HSeAs阴性组在高病毒载量组(HBV DNA105拷贝/m1)的比例低于HBeAg阳性组(37.4%VS55.6%,P=0.001).结论 HBeAg阴性患者与HBeAg阳性患者相比存在年龄偏大和HBV DNA水平较低等特征,HBeAg阴性乙肝患者的病情有时反而可能较重.     

HBeAg阴性与阳性慢性乙肝患者的临床对比分析

目的 探讨HBeAg阳性和HBeAg阴性慢性乙肝患者的临床特征异同.方法 随机选取慢性乙肝患者354例,其中HBeAg阳性组124例,HBeAg阴性组230例,对两组的人口学、生化学、病毒学及诊断分型进行分析比较.结果 ①与HBeAg阳性组比较,HBeAg阴性组患者年龄较大(P=0.000),中度和重度慢性肝炎比例较低(P:0.007和0.014),重型肝炎发生率较高(P=0.008).②HBeAg阴性组的ALT、ALB、PTA及HBV DNA载量对数值低于HBeAg阳性组(P=0.035,0.002,0.000和0.000),但TBil水平高于HBeAg阳性组(P=0.003);两组AST水平差异无统计学意义(P=0.222).③HSeAs阴性组在高病毒载量组(HBV DNA105拷贝/m1)的比例低于HBeAg阳性组(37.4%VS55.6%,P=0.001).结论 HBeAg阴性患者与HBeAg阳性患者相比存在年龄偏大和HBV DNA水平较低等特征,HBeAg阴性乙肝患者的病情有时反而可能较重.     

HBV感染者基因型、HBVDNA、HBV cccDNA、ALT血清水平变化与抗病毒治疗相关性分析

为检测HBV感染者基因型及血清HBV DNA、HBV cccDNA、ALT、HBeAg水平,探讨它们之间相互关系及治疗后与这些指标的相关性,采用PCR荧光定量、基因测序、化学发光、生化分析等方法,分别对收集的202例HBV感染的患者Lamivudine抗病毒治疗前后的血清HBV DNA、HBV cccDNA、 ALT、 HBeAg定量检测及HBV DNA基因分型.结果显示,HBV B型和C型患者的血清 HBV DNA和cccDNA的水平没有显著性差异,HBV cccDNA与HBV DNA的比值也没有显著性差异;HBV B型和C型患者的血清 HBV DNA和cccDNA的水平与ALT有相关性;不管是HBV B型还是C型的患者,HBeAg阳性的患者血清中HBV DNA和cccDNA显著高于HBeAg阴性的患者;但是,C型的患者,HBeAg阳性的患者cccDNA与HBV DNA的比值显著低于HBeAg阴性的患者;治疗后比治疗前除 HBeAg没有显著性差异(P>0.05),HBV DNA、cccDNA、ALT均有显著性差异(P<0.01).感染HBV B型和C型的患者血清 HBV DNA和cccDNA的水平无显著性差异;而C型的患者,HBeAg阳性的患者cccDNA与HBV DNA的比值显著低于HBeAg阴性的患者;HBV DNA基因型、HBV cccDNA、ALT与抗病毒治疗密切相关.     

A European multicientre study on the comparison of HBV viral loads between VERIS HBV assay and Roche COBAS® TAQMAN® HBV test,Abbott RealTime HBV assay,Siemens VERSANT HBV assay,and Qiagen artus HBV RG kit

BackgroundHepatitis B viral load testing is essential to treatment and monitoring decisions in patients with chronic Hepatitis B. Beckman Coulter has developed the VERIS HBV Assay (Veris) for use on the fully automated DxN VERIS Molecular Diagnostics System.¹ObjectivesTo evaluate the clinical performance of the Veris HBV Assay at multiple EU laboratoriesStudy designMethod comparison was performed with a total of 344 plasma specimens from HBV infected patients tested with Veris and COBAS^® TaqMan^® HBV Test (Cobas), 207 specimens tested with Veris and RealTime HBV Assay (RealTime), 86 specimens tested with Veris and VERSANT^® HBV Assay (Versant), and 74 specimens tested with Veris and artus^® HBV RG PCR kit (artus).ResultsBland-Altman analysis showed average bias of −0.46 log₁₀ IU/mL between Veris and Cobas, −0.46 log₁₀ IU/mL between Veris and RealTime, −0.36 log₁₀ IU/mL between Veris and Versant, and −0.12 log₁₀  IU/mL between Veris and artus. Bias was consistent across the assay range. Patient monitoring results using Veris demonstrated similar viral load trends over time to Cobas, RealTime, and artus.ConclusionsThe VERIS HBV Assay demonstrated comparable clinical performance, with varying degrees of negative bias, compared to other currently marketed assays for HBV DNA monitoring. This negative bias should be taken into consideration if switching monitoring methods to Veris.     

High rate of Hepatitis B virus infection among hairdressers in Ibadan,Nigeria

Hepatitis B virus (HBV) infection is a major public health problem for over two billion people infected globally. Occupationally exposed persons are at high risk of HBV infection and, apart from medical personnel, there is dearth of information concerning the prevalence and awareness of HBV among this population in Nigeria. This study was designed to determine the levels of HBV awareness and prevalence of HBV infection among hairdressers in Ibadan, Nigeria. Hairdressers and teachers (unmatched controls) in four local government areas in Ibadan were tested for HBV infection using ELISA technique. Dried blood spot (DBS) samples were collected from 171 participants. DBS elutes from the samples were tested for HBV surface antigen (HBsAg). The rate of HBV infection was higher (p = 0.005) among the hairdressers (13.0%) than teachers (4.8%). However, teachers were better informed about HBV (38%) compared to hairdressers (13%; p = 0.0001). Differences in HBV awareness and occupation type were found to be significant (P = 0.001). Hairdressers are at high risk of HBV infection and may constitute a major source of HBV spread among urban dwellers, especially in areas where awareness is low. Routine HBV screening and appropriate interventions for hairdressers are recommended to interrupt HBV transmission.     

Hepatitis B virus DNA in liver, serum, and peripheral blood mononuclear cells after the clearance of serum hepatitis B virus surface antigen

The integration of hepatitis B virus (HBV) DNA in the liver of chronic HBV carriers has been documented extensively. However, the status of the viral genome during acute infection has not been assessed conclusively. While HBV DNA sequences are detected often in serum, liver, and peripheral blood mononuclear cells (PBMCs) after the clearance of serum the hepatitis B virus surface antigen (HBsAg), the precise status of the viral genome, and in particular the possible persistence of integrated genomes in PBMCs, has not been established. A highly sensitive PCR-derived assay (Alu-PCR) was employed to re-examine liver and PBMC specimens obtained from patients with acute (n = 19) and chronic (n = 22) hepatitis in whom serum HBsAg was present (n = 12) (HBV-related chronic active hepatitis) or absent with anti-HCV (n = 10) (HCV-related chronic active hepatitis). Viral integration was demonstrated in 3 out of 19 liver specimens from patients with acute hepatitis and 12 out of 12 specimens from patients with chronic hepatitis. Viral integration was also observed in 4 out of 7 PBMC samples from HBV-related chronic active hepatitis patients and 2 out of 10 liver and PBMC samples from HCV-related chronic active hepatitis patients. In one liver specimen from an acute hepatitis patient, HBV DNA was found integrated in the intronic sequence of the tumour necrosis factor (TNF)-induced protein gene; viral integration into cellular sequences was also found in the PBMCs of four HBV-related chronic active hepatitis and two HCV-related chronic active hepatitis. The results demonstrate the early integration of HBV genome during acute viral infections and the persistence of the viral genome in an integrated form in PBMCs.     

HBV-前S_2抗原单克隆抗体制备、特性和应用

用HBsAg制备了一株分泌乙型肝炎病毒前S_2抗原单克隆抗体(MAb)的杂交瘤细胞株(1E_2),小鼠腹水中MAb效价达10~7。1E_2MAb有很强的抑制多聚人血清白蛋白(pHSA)和HBsAg中前S_2抗原结合的能力;与重组痘菌病毒表达的中分子蛋白(含S和前S_2抗原)而不与小分子蛋白(含S抗原)反应;与人工合成的前S_2肽段(N端12O-146氨基酸序列)特异性结合。应用1E_2MAb的酶免疫法检测乙肝病毒感染者血清中前S_2抗原,表明前S_2抗原滴度和HBsAg滴度有较好的相关性,在EBeAg阳性血清中更为明显;HBeAg阳性血清前S_2抗原的阳性率和几何平均滴度明显高于HBeAg阴性/HBsAg阳性血清。     

Hepatitis B virus prevalence,risk factors and genotype distribution in HIV infected patients from West Java,Indonesia

BackgroundIndonesia currently faces both an increasing HIV incidence and a high hepatitis B virus (HBV) burden.ObjectiveThe objective of our study is to examine the prevalence, risk factors, and genotypic distribution of HBV infection among HIV infected patients in West Java, Indonesia.Study designA cross sectional study was conducted among a cohort of HIV infected patients in 2008. Demographic and disease related variables were compared between HBV negative and positive patients. Logistic regression was applied to determine risk factors for HBV co-infection. HBV and HIV genotyping was performed in co-infected patients.ResultsOf 636 HIV-infected patients, the rate of HBV co-infection was 7%. The proportion of males was higher in HBV/HIV co-infected patients than in HIV mono-infected patients (93% vs. 72%, P = 0.001). A history of injecting drug use (IDU), but not tattooing, was associated with HBV co-infection [P = 0.035 OR 2.41 (95% CI 1.06–5.47)]. In the HIV and HBV treatment naive patients, CD4 cells counts <50 cells/mm³, HIV-RNA plasma ≥10,000 copies/ml and AST level above normal were more often found in patients with high HBV-DNA levels (≥20,000 IU/ml) as compared to those with low HBV DNA (<20.000  IU/ml) (P < 0.05). As in the general population, B3 was the dominant subtype in HBV co-infected patients.ConclusionThe prevalence of active HBV infection and the genotype distribution among HIV infected individuals is similar to the overall population in Java. However, an increased prevalence was observed in men with a history of IDU, underlining the need for routine HBV screening and monitoring.     

Low incidence and high titers of antibodies to hepatitis B virus X-protein in sera of Chinese patients with hepatocellular carcinoma

Sera of patients from China with hepatocellular carcinoma (HCC) were tested for the presence of HBc/HBe- and HBx antibodies by immunoblotting using recombinant MS2 or beta gal fusion proteins as substrate. Antibodies against HBx were detected in four out of 68 HBsAg positive and in one out of three HBsAg negative sera, antibodies against HBc/HBe in 52 and two serum samples, respectively. Competition experiments in which sera were preincubated with individual viral proteins synthesized in E. coli were carried out to demonstrate the specificity of signals obtained in immunoblot analyses. In the five anti-HBx positive sera, the antibody titer against X fusion protein was higher than against core fusion protein and in one of these sera anti-x activity could be demonstrated even at a serum dilution of 1:50,000. These data indicate that X antibodies occur rarely in Chinese patients and are not serodiagnostic for HCC. The high titer of X antibodies in some patients shows that the X protein can be highly immunogenic in vivo. Induction of antibody formation may be triggered by X protein expressed from integrated viral DNA.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.