基线Anti-HBc联合HBsAg预测聚乙二醇干扰素α-2a在恩替卡韦经治慢性乙型肝炎的治疗应答

目的探究使用恩替卡韦治疗96周后序贯聚乙二醇干扰素α-2a对慢性乙型肝炎的治疗中基线Anti-HBc在HBeAg血清学转换的预测作用。方法纳入103例经恩替卡韦单药治疗的慢性乙型肝炎患者并将其随机分为对照组和试验组,其中试验组56例,在恩替卡韦治疗基础上序贯聚乙二醇干扰素α-2a,12周后改为单药使用聚乙二醇干扰素α-2a;对照组47例,持续接受单药恩替卡韦治疗。每12周进行血常规、甲状腺功能、肝功能检测;采用电化学发光法检测HBsAg、Anti-HBs、HBeAg、Anti-HBe含量,ELISA检测Anti-HBc,荧光定量PCR法检测HBV DNA含量,并比较治疗48周后两组HBeAg血清转换率和HBsAg消失率。结果治疗12周,对照组HBsAg的中位数值相对稳定,试验组呈下降趋势;治疗48周,试验组较对照组HBeAg血清转换率和HBsAg消失率皆有所提高。结论结合基线Anti-HBc定量和HBsAg可作为预测疗效的指标,观察远期疗效。

四种乙肝标志物ELISA试剂盒的动力学比较研究

目的 观察和评价四种 ELISA试剂盒的动力学过程 ,并对 4种试剂进行动力学评价。方法 将系列定值血清进行倍比稀释 ,用 4种乙肝标志物试剂盒分别检测 HBs Ag、Anti- HBs、HBe Ag、Anti- HBe和 Anti- HBc,对检验结果进行统计分析。结果 4种试剂盒灵敏度、线性、本底等不尽一致 ,A试剂相对较好 ;Anti- HBe和 Anti- HBc的 CO值位于成长曲线上平台附近 ;立可读 (C)试剂的灵敏度偏低。结论 ELISA反应的成长曲线与检测标本的取值范围密切相关 ,在确定拟合曲线前应充分考虑研究对象的分布特性 ;所观察试剂的质量有一定差异 ,特别是 C试剂的灵敏度偏低。

乙型肝炎核心抗体放射免疫定量试剂盒的研制

以聚苯乙烯小球为固相载体,在小球表面包被一层基因工程制备的乙型肝炎核心抗原(HBcAg),以125I标记的乙型肝炎核心抗体(125I-Anti-HBc)作为标记物,采用固相放射免疫竞争法研制成乙型肝炎核心抗体放射免疫定量试剂盒(Anti-HBc-RIA)。本试剂盒的灵敏度为0.8NCU/mL,批内变异系数<9.9%,批间变异系数<13.8%,回收率为92.6%～109.2%。正常参考值为0～2.0NCU/mL。

HBsAg自然转阴的慢性HBV感染者临床特征

目的分析HBsAg自然转阴的慢性HBV感染者的临床特征。方法纳入2014年9月至2016年5月在延安大学附属医院感染病科门诊就诊以及住院的HBsAg已经自然转阴(通过化学发光法检测HBsAg<0.05 IU/mL)的慢性HBV感染者85例。收集患者的一般资料(包括年龄、性别)、肝功能、腹部B超、乙型肝炎病毒定量、乙型肝炎血清标志物定量,并对所得各项数据进行统计分析。结果 85例HBsAg自然转阴的慢性HBV感染者中男性57例(67.1%),女性28例(32.9%)。年龄21~73岁,平均年龄(47.7±12.1)岁。抗-HBs与ALT、AST的Pearson直线相关系数分别为-0.013(P>0.05)、-0.075(P>0.05)。抗-HBc与ALT、AST的Pearson直线相关系数分别为0.190(P>0.05)、-0.008(P>0.05)。抗-HBc与HBsAg的Pearson直线相关系数为-0.559(P=0.000)。HBsAg转阴时年龄(≤50岁与>50岁者)与不同病情患者例数的行×列表分析的χ~2为29.509(P=0.000)。结论抗-HBs与ALT、AST无相关性,即抗-HBs升高,不预示肝功能损伤;抗-HBc与ALT、AST无相关性,即抗-HBc升高,不预示肝功能损伤;抗-HBc升高,HBsAg下降,提示抗-HBc水平升高预示HBsAg转阴的可能性;50岁以前HBsAg转阴患者预后较50岁以后HBsAg转阴患者发生肝硬化、肝细胞癌(HCC)的几率小。

乙型肝炎表面抗原阳性5个月且尿蛋白阳性

1病例简介患者,男,31岁。主因＂肝区不适1年,发现乙型肝炎表面抗原阳性5个月＂于2011年10月9日入院。患者1年前自觉肝区不适,伴有双肾区不适,无乏力、食欲不振、恶心、呕吐、腹胀等;无眼黄、尿黄;无颜面、双下肢水肿。5个月前于本院门诊查乙肝系列,提示大三阳（HBsAg〉250IU/ml,HBeAg1366.37S/CO,Anti-HBc 10.68S/CO）,肝功能正常,

Diagnostic strategy for occult hepatitis B virus infection

In 2008,the European Association for the study of the liver(EASL) defined occult hepatitis B virus infection (OBI) as the"presence of hepatitis B virus(HBV) DNA in the liver(with detectable or undetectable HBV DNA in the serum) of individuals testing hepatitis B surface antigen(HBsAg) negative by currently available assays".Several aspects of occult HBV infection are still poorly understood,including the definition itself and a standardized approach for laboratory-based detection,which is the purpose of this review.The clinical significance of OBI has not yet been established;however,in terms of public health,the clinical importance arises from the risk of HBV transmission.Consequently,it is important to detect high-risk groups for occult HBV infection to prevent transmission.The main issue is,perhaps,to identify the target population for screening OBI.Viremia is very low or undetectable in occult HBV infection,even when the most sensitive methods are used,and the detection of the viral DNA reservoir in hepatocytes would provide the best evaluation of occult HBV prevalence in a defined set of patients.However,this diagnostic approach is obviously unsuitable:blood detection of occult hepatitis B requires assays of the highest sensitivity and specificity with a lower limit of detection<10 IU/mL for HBV DNA and<0.1 ng/mL for HBsAg.

Pathogenesis of occult chronic hepatitis B virus infection

Occult hepatitis B infection(OBI) is characterized by hepatitis B virus(HBV) DNA in serum in the absence of hepatitis B surface antigen(HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns.Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays;but more frequently it is due to a strong suppression of viral replication and gene expression.OBI is an entity with world-wide diffusion.The failure to detect HBsAg,despite the persistence of the viral DNA,is due in most cases to the strong suppression of viral replication and gene expression that characterizes this"occult"HBV infection;although the mechanisms responsible for suppression of HBV are not well understood.The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection.Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

Prevalence of occult hepatitis B virus infection

Occult hepatitis B virus(HBV) infection(OBI) is characterized by the persistence of HBV DNA in the liver tissue in individuals negative for the HBV surface antigen.The prevalence of OBI is quite variable depending on the level of endemic disease in different parts of the world,the different assays utilized in the studies,and the different populations studied.Many studies have been carried out on OBI prevalence in different areas of the world and categories of individuals.The studies show that OBI prevalence seems to be higher among subjects at high risk for HBV infection and with liver disease than among individuals at low risk of infection and without liver disease.

Occult hepatitis B virus infection among Egyptian blood donors

AIM:To identify blood donors with occult hepatitis B virus(HBV) infection(OBI) to promote safe blood donation.METHODS:Descriptive cross sectional study was conducted on 3167 blood donors negative for hepatitis B surface antigen(HBsAg),hepatitis C antibody(HCV Ab) and human immunodeficiency virus Ab.They were subjected to the detection of alanine aminotransferase(ALT) and aspartate transaminase(AST) and screening for anti-HBV core antibodies(total) by two different techniques;[Monoliza antibodies to hepatitis B core(Anti-HBc) Plus-Bio-Rad] and(ARC-HBc total-ABBOT).Positive samples were subjected to quantitative detection of antibodies to hepatitis B surface(anti-HBs)(ETI-AB-AUK-3,Dia Sorin-Italy).Serum anti-HBs titers > 10 IU/L was considered positive.Quantitative HBV DNA by real time polymerase chain reaction(PCR)(QIAGEN-Germany) with 3.8 IU/mL detection limit was estimated for blood units with negative serum anti-HBs and also for 32 whose anti-HBs serum titers were > 1000 IU/L.Also,265 recipients were included,34 of whom were followed up for 3-6 mo.Recipients were investigated for ALT and AST,HBV serological markers:HBsAg(ETI-MAK-4,Dia Sorin-Italy),anti-HBc,quantitative detection of anti-HBs and HBV-DNA.RESULTS:525/3167(16.6%) of blood units were positive for total anti-HBc,64% of those were antiHBs positive.Confirmation by ARCHITECT anti-HBc assay were carried out for 498/525 anti-HBc positive samples,where 451(90.6%) confirmed positive.Reactivity for anti-HBc was considered confirmed only if two positive results were obtained for each sample,giving an overall prevalence of 451/3167(14.2%) for total anti-HBc.HBV DNA was quantified by real time PCR in 52/303(17.2%) of anti-HBc positive blood donors(viral load range:5 to 3.5 x 105 IU/mL) with a median of 200 IU/mL(mean:1.8 x 104 ± 5.1 x 104 IU/mL).AntiHBc was the only marker in 68.6% of donors.Univariate and multivariate logistic analysis for identifying risk factors associated with anti-HBc and HBV-DNA positivity among blood donors showed that age above thirty and marriage were the most significant risk factors for prediction of anti-HBc positivity with AOR 1.8(1.4-2.4) and 1.4(1.0-1.9) respectively.Other risk factors as gender,history of blood transfusion,diabetes mellitus,frequent injections,tattooing,previous surgery,hospitalization,Bilharziasis or positive family history of HBV or HCV infections were not found to be associated with positive anti-HBc antibodies.Among anti-HBc positive blood donors,age below thirty was the most significant risk factor for prediction of HBV-DNA positivity with AOR 3.8(1.8-7.9).According to HBV-DNA concentration,positive samples were divided in two groups;group one with HBV-DNA ≥ 200 IU/mL(n = 27) and group two with HBV-DNA < 200 IU/mL(n = 26).No significant difference was detected between both groups as regards mean age,gender,liver enzymes or HBV markers.Serological profiles of all followed up blood recipients showed that,all were negative for the studied HBV markers.Also,HBV DNA was not detected among studied recipients,none developed post-transfusion hepatitis(PTH) and the clinical outcome was good.CONCLUSION:OBI is prevalent among blood donors.Nucleic acid amplification/HBV anti core screening should be considered for high risk recipients to eliminate risk of unsafe blood donation.

安抗-Ⅰ注射液对乙型肝炎病毒标志物的影响

近年来乙型肝炎的药物治疗取得了一些进展，但仍无特异性药物面世，乙肝病毒血清标志物的转阴治疗亦无重大突破。安抗-Ⅰ注射液(抗乙肝转移因子）是一种抗乙肝病毒新药，为探索安抗-Ⅰ注射液(抗乙肝转移因子)对血清乙肝病毒标志物的影响，我们对HBsAg、HReAg和Anti-HBc同时阳性的慢性乙型肝炎和乙肝病毒携带者共60例进行了对照一治疗观察，现将结果报告如下：

TERATOGENIC EFFECT OF ANTI-HBs-A CONCURRENT COHORT STUDY

One thousand, five hundred and seventy six pregnant women were followed upprospectively from early pregnancy to investigate the relation or Anti-HBs and other 10 risk factors from pregnant women with the congenital malformation of newborn. The results confirmed the teratogenic effect of Anti-HBs. The monofactorial analysis showed that the newborn congenital malformationincidence in Anti-HBs positive mothers was higher than that in Anti-HBs negative mothers (x2=6. 0274,P = 0.0141). The multifactorial analysis by using unconditional Logistic Repression model confirmed that Anti-HBs had a teratogenic effect (OR=5. 30952, P=0. 000302). The possibleteratogenic mechanism of Anti-HBs is discussed. It is important to further study the teratogenic effect of Anti-HBs in eugenics. Anti-HBc may have prevention effect on congenital malformation development (OR= 0. 27110, P= 0. 004515). In addition, exposure to toxicants during pregnancy is one of the risk factors causing congenital malformation (OR= 8. 17080, P=0. 001780).

Hepatitis B virus markers in hepatitis B surface antigen negative patients with pancreatic cancer:Two case reports

BACKGROUND Hepatitis B virus(HBV)is a known carcinogen that may be involved in pancreatic cancer development.Detection of HBV biomarkers[especially expression of HBV regulatory X protein(HBx)]within the tumor tissue may provide direct support for this.However,there is still a lack of such reports,particularly in non-endemic regions for HBV infection.Here we present two cases of patients with pancreatic ductal adenocarcinoma,without a history of viral hepatitis,in whom the markers of HBV infection were detected in blood and in the resected pancreatic tissue.CASE SUMMARY The results of examination of two patients with pancreatic cancer,who gave informed consent for participation and publication,were the source for this study.Besides standards of care,special examination to reveal occult HBV infection was performed.This included blood tests for HBsAg,anti-HBc,anti-HBs,HBV DNA,and pancreatic tissue examinations with polymerase chain reaction for HBV DNA,pregenomic HBV RNA(pgRNA HBV),and covalently closed circular DNA HBV(cccDNA)and immunohistochemistry staining for HBxAg and Ki-67.Both subjects were operated on due to pancreatic ductal adenocarcinoma and serum HBsAg was not detected.However,in both of them anti-HBc antibodies were detected in blood,although HBV DNA was not found.Examination of the resected pancreatic tissue gave positive results for HBV DNA,expression of HBx,and active cellular proliferation by Ki-67 index in both cases.However,HBV pgRNA and cccDNA were detected only in case 1.CONCLUSION These cases may reflect potential involvement of HBV infection in the development of pancreatic cancer.

Hepatitis B Surface Antigen Should Not Be the Only Sought Marker to Distinguish Blood Donors towards Hepatitis B Virus Infection in High Prevalence Area

Since its discovery by Blumberg in 1965, the hepatitis B surface antigen (HBsAg) is used as the fingerprint of hepatitis B infection. Occult hepatitis B infection (OBI) is defined by a viral replication (DNA detectable) in the absence of HBsAg. Burkina Faso is a high endemic area where the prevalence is higher than 14%. At the National Center for Blood Transfusion (NCBT) of Ouagadougou, HBsAg is the only sought marker used to distinguish donors towards Hepatitis B Virus (HBV). Acceptation of blood donation is based specifically on the absence of HBsAg, which exposes to the risk of HBV transmission during transfusion. The goal of this study is to evaluate this risk by determining the prevalence of OBI in blood donors. Patients and Methods: It was a five-month prospective study on blood donations collected from January to May 2016. The HBc antibody has been sought in the serums of negative HBsAg donors. The measure of B DNA by Real Time PCR (polymerase chain reaction) and that of antibodies anti-HBs have been proposed to anti-HBc positive donors. Abdominal ultrasound, the transaminases, prothrombin level, alphafeto-proteins, hepatic fibrosis have been proposed to donors who were detectable for the DNA. Sociodemographic parameters have been collected. The test costs were borne by donors who were recalled by phone to adhere to the study. Results: Among 1980 negative donors HBsAg, 872 (44%) were positive for anti-HBc. 160 on 872 donors were received for consultation, among which 76 (76/160) were able to realise DNA which was detectable in 25 donors on 76, thus a prevalence of 32.8%. The mean value of DNA was 953 IU/ml. Physical examination and hepatic ultrasounds were normal except a case where hepatic steatosis was found. The biologic standard hepatic results were in normal range. None of the patient was able to realise hepatic fibrosis evaluation. A case of co-infection HIV/OBI was noted. Conclusion: This study shows that in Burkina, almost half of blood bags transfused are anti-HBc positive and around one third (32.8%) probably have HBV DNA. This poses a potential risk of contamination for non-immunized recipient. It is thus important that, in addition to HBsAg, Anti-HBc should be systematically sought in order to minimize the risk.

2658份血清标本中anti-HBs、anti-HBe、anti-HBc分布模式及形成机制的探讨

目的:探讨HBV病毒急慢性感染过程中抗体类标志物的分布模式及形成机制。方法:采用化学发光微粒子免疫检测法(CMIA法)定量分析2012年2月10日-6月10日来我院就诊的2658例门诊或住院患者的血清标本中的HBV病毒感染标志物,根据抗原性标志物实验结果将抗体类标志物实验结果的分布模式分组进行统计学分析。结果:发现HBsAg无反应性组(N)内单纯anti-HbsIgG与有反应性分布差异有统计学意义;HBsAg有反应性组anti-HBeIgG+anti-HBcIgG有反应性分布与另两组组间比较差异有统计学意义(P<0.05);anti-HBsIgG、anti-HBcIgG、anti-HBeIgG表达含量在各实验组存在着差异。anti-HBcIgG含量在HBsAg(N)+anti-HBs(R)组和HBsAg(N)+anti-HBc(R)组差异有统计学意义(P<0.05);anti-HBe(S/CO)在HB-sAg(R)+anti-HBe(R)+anti-HBc(R)组和HBsAg(R)+HBeAg(R)+anti-HBc(R)差异有统计学意义(P<0.01);an-ti-HBc(S/CO)在HBsAg(R)+anti-HBe(R)+anti-HBc(R)组和HBsAg(R)+HBeAg(N)+anti-HBc(R)差异有统计学意义P<0.05。结论:HBV感染标志物不仅可以诊断HBV病毒急慢性感染,还可对疾病病程分层,指导治疗评价预后。

The Study of IgG Subclass Profiles of Anti-HBc in Populations with Different Status of HBV Infection

To study IgG subclasses for the hepatitis B virus （HBV） core antigen （anti-HBc） in different populations, a comparison was made between 104 chronic carriers （60 male and 44 female） and 434 recovered individuals （247 male and 192 female）. Biochemistry analyses of AST （aspartate aminotransferase） and ALT （alanine aminotransferase） were also performed. Among the 104 chronic carriers, 21 patients were found to be ALT and AST abnormal （〉 25 IU/ml）. After comparing these ALT and AST abnormal patients with other ALT and AST normal chronic carriers, no statistical difference was observed in the OD values of the anti-HBe （p 〉 0.05）. The ELISA results showed the anti-HBc IgG subclass pattern was IgG1 〉 IgG3 〉 IgG4 in chronic carriers and IgG3 〉 IgG1 〉 IgG4 in recovered individuals （p 〈 0.05）. This result suggests the IgG1/IgG3 ratio may be related with HBV status. However, in spite of the different anti-HBc IgG1/IgG3 patterns demonstrated in different populations, both anti-HBc IgG1 and IgG3 concentrations were significantly higher in chronic carriers （p 〈 0.05）. Therefore, both the anti-HBc IgG1/IgG3 ratio and their amounts differed. They may play a significant role in chronic carriers and recovered individuals. The anti-HBc IgG subclass profiles of chronic carriers were not changed regardless of liver inflammation, and were independent of sex and age.

深圳市大鹏新区实施乙肝疫苗免疫策略后乙肝血清流行病学变化

目的 分析深圳市大鹏新区实施乙肝疫苗免疫策略后乙肝血清流行病变化。方法 采取整群随机抽样调查方法,在深圳市大鹏新区抽取1-20岁年龄段的人群1 000例,分析实施乙肝疫苗免疫策略前后乙肝血清病学变化。结果实施乙肝疫苗免疫策略后,1-20岁人群HBsAg阳性率为1.21%,不同年龄段比较差异无统计学意义（P〉0.05）;Anti-HBs阳性率为72.17%,不同年龄段比较差异有统计学意义（P〈0.01）,Anti-HBc阳性率为2.33%,不同年龄段比较差异有统计学意义（P〈0.01）;男、女HBsAg、Anti-HBs、Anti-HBc阳性率分别为1.04%、70.10%、2.49%及1.40%、74.16%、2.17%,不同性别之间比较差异无统计学意义（P〉0.05）;实施后HBsAg、Anti-HBc阳性率明显低于实施前（1.21%vs.5.71%、2.33%vs.12.68%）,Anti-HBs阳性率明显高于实施前（72.17%vs.21.96%）。结论 深圳市大鹏新区1-20岁人群实施乙肝疫苗免疫策略后乙肝血清流行病变化有助于建立较高的免疫屏障。