从159例HBsAg、Anti-HBs的测定谈乙型肝炎免疫预防的必要性

目的 对 15 9份血清进行HBsAg ,Anti -HBs检测 ,并进一步分析乙型肝炎 (以下简称乙肝 )的预防。 方法 HBsAg ,Anti-HBs的测定用ELISA法。结果 HBsAg携带者为 13人 ,无免疫力者为 78人 ,Anti-HBs阳性 6 8人。结论 血清学测定HBsAg .Anti-HBs对于及早发现乙肝病毒携带者或易感者有准确的效果 ,对于乙肝的防治有较好的辅助作用。

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).

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。

孕期注射乙肝免疫球蛋白对婴儿anti-HBs产生的影响

目的探讨孕期注射乙肝免疫球蛋白的孕妇分娩的婴儿对乙肝疫苗免疫应答情况。方法以HBsAg阳性孕妇及其新生儿为研究对象,孕期母亲注射乙肝免疫球蛋白的300例新生儿为实验组,未使用者80例为对照组,比较两组新生儿出生时及联合免疫后7个月anti-HBs产生情况。结果实验组与对照组婴儿出生时anti-HBs阳性率分别为10.3%(31/300)和1.25%(1/80),差异有统计学意义;7个月龄实验组anti-HBs产生率为96.1%(124/129),对照组anti-HBs产生率95.3%(41/43),差异无统计学意义;出生时anti-HBs阳性的新生儿25例,7个月龄均产生anti-HBs,出生时anti-HBs阴性或弱阳性的147例婴儿中有7例婴儿anti-HBs仍为阴性或弱阳性,差异有统计学意义。结论孕期使用乙肝免疫球蛋白可提高新生儿出生时anti-HBs产生率,但对7个月anti-HBs产生率无影响。

Immunization against Hepatitis B Virus: Serological Status of West African Populations Residing in Cotonou (Benin) and Dakar (Senegal)

Background: According to WHO estimates, by 2022 over 296 million people are living with chronic hepatitis B virus (HBV) infection, and over 820,000 have died from complications. In sub-Saharan African countries such as Benin and Senegal, few research studies have addressed the issue of HBV immunization. Objective: The main objective of this study was to evaluate immunization against the hepatitis B virus in populations residing in Cotonou and Dakar by titrating anti-HBs antibodies (Ab) and detecting total anti-HBc immunoglobulins (Ig). Materials and Methods: This was a prospective, descriptive, analytical study of two West African populations recruited in Dakar at the Laboratory of Medical Biology (LBM) of the General Hospital Idrissa Pouye (HOGIP) and in Cotonou at the LBMs of the health centres of the Cotonou archdiocese. HBsAg-negative patients constituted our study population. The study took place in November-December 2019 for Dakar and February-March 2020 for Cotonou. Anti-HBs antibodies were tested and titrated. In the event of anti-HBs positivity, total anti-HBc was determined. A microparticle chemiluminescence immunoassay was used for marker determination. The detection threshold was 2.50 IU/L for anti-HBs. Excel and IBM SPSS Statistics software were used for data analysis. Subjects’ sociodemographic characteristics were collected using a questionnaire, as was knowledge of their vaccination status. The study was approved by the ethics committees in Benin and Senegal. Results: A total of 394 HBs antigen-negative participants were recruited: 205 in Cotonou and 189 in Dakar. The population was predominantly female, with 65.36% (N = 134) and 57.14% (N = 108) women in Cotonou and Dakar respectively. The median age of participants was 29 years in Cotonou, with extremes of 10 and 65 years, versus 39 years in Dakar, with extremes of 6 and 93 years. Some participants claimed to be unaware of their vaccination status: 33.17% in Cotonou and 56.61% in Dakar. The total prevalence of anti-HBs-positive subjects was 88.78% (N = 182) in Cotonou and 98.41% (N = 186) in Dakar. In Cotonou (N = 205), 35.61% (N = 73) of subjects had protective anti-HBs levels between 11.60 IU/L and 10,000 IU/L. In Dakar, 61.38% (N = 116) of subjects had protective HBV immunity, with anti-HBs titres ranging from 10.30 IU/L to 11357 IU/L. In Cotonou, 80.82% (N = 59) of immunized subjects (N = 73) had anti-HBC antibodies, compared with 84.48% (N = 98) of immunized individuals (N = 116) in the population recruited in Dakar, indicating immunization following HBV infection. Conclusion: Our study involved a predominantly female population, many of whom were unaware of their serological status. Vaccination policies and knowledge of the viral hepatitis B epidemic need to be strengthened.

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。

血清25-羟维生素D水平与儿童免疫功能和反复呼吸道感染的关联性分析

背景高水平的25-羟维生素D〔25(OH)D〕维持着人体骨骼系统外细胞25(OH)D受体的正常新陈代谢,与血液循环系统、呼吸系统、结缔组织及自身免疫疾病和肿瘤的发展密切相关,相关研究表明,每天补充4000 U的25(OH)D3可显著减少免疫缺陷患儿的感染症状、鼻拭子中的致病菌数量、对抗生素的消耗,减少儿童由于免疫功能不完善导致反复呼吸道感染的发生。目的对反复呼吸道感染儿童的血清25(OH)D水平在不同IgG和IgM水平患儿中的分布差异及与乙肝抗体(anti-HBs)滴度和反复呼吸道感染次数之间的关联性进行分析,为25(OH)D补充剂在减少儿童反复呼吸道感染中的实际应用提供线索。方法选取2016年8月—2018年10月于安徽医科大学第一附属医院接受治疗的反复呼吸道感染患儿146例,根据年龄分为0~<2岁组、2~<6岁组、6~<12岁组、12~16岁组,比较各年龄组血清25(OH)D水平;根据研究对象的血清IgG、IgM水平分为IgG降低组79例、IgG正常组38例及IgG升高组30例,IgM降低组92例、IgM正常组29例及IgM升高组25例,比较各组间血清25(OH)D水平;采用泊松回归分析对血清25(OH)D水平与儿童反复呼吸道感染次数进行关联性分析。结果0~<2岁组血清25(OH)D水平高于2~<6岁组、6~<12岁组和12~16岁组(q=5.202、6.030、8.432,P值均<0.001);2~<6岁组和6~<12岁组血清25(OH)D水平高于12~16岁儿童(q=5.317、5.559,P值均<0.05)。泊松回归分析结果显示,血清25(OH)D水平与儿童反复呼吸道感染次数呈现负向关联〔FR=0.94,95%CI(0.89,1.02),P=0.048〕。结论儿童的血清25(OH)D水平与血清anti-HBs滴度无相关关系,与反复呼吸道感染次数呈现负向关联。

淮安市淮阴区健康人群乙型肝炎免疫状况分析

目的:了解健康人群乙型肝炎免疫状况。方法:检测淮安市淮阴区健康人群乙型肝炎表面抗原(HBsAg)和乙型肝炎表面抗体(Anti-HBs)。结果:人群HBsAg阳性标化率4.94%,Anti-HBs阳性标化率29.78%。结论:及时接种乙肝疫苗对控制乙肝流行、降低人群HBsAg阳性率起到了决定性作用。

High prevalence of hepatitis B-antibody loss and a case report of de novo hepatitis B virus infection in a child after living-donor liver transplantation

AIM To assess the seroprevalence of hepatitis B virus(HBV) immunity among previously vaccinated pediatric liver transplant recipients and present a case report of de novo hepatitis B infection after liver transplantation.METHODS This study focused on children with chronic liver diseases who received primary hepatitis B immunization and had a complete dataset of anti-HBs before and after liver transplantation between May 2001 and June 2017. Medical records were retrospectively reviewed for potential factors relating to HBV immunity loss. RESULTS In total, 50 children were recruited. The mean time from liver transplantation to anti-HBs testing was 2.53 ± 2.11 years. The mean anti-HBs levels before and after liver transplantation were 584.41 ± 415.45 and 58.56 ± 6.40 IU/L, respectively. The rate of nonimmunity(anti-HBs < 10 IU/L) in the participants was 46%(n = 26) at one year, 57%(n = 7) at two years and 82%(n = 17) at > three years following liver transplantation. The potential factors relating to HBV immunity loss after liver transplantation were identified as anti-HBs(P = 0.002), serum albumin(P = 0.04), total bilirubin(P = 0.001) and direct bilirubin(P = 0.003) before liver transplantation. A five-year-old boy with biliary cirrhosis received 4 doses of HBV vaccine with an anti-HBs titer of > 1000 IU/L and underwent liver transplantation; his anti-HBc-negative father was the donor. After liver transplantation, the boy had stenosis of the hepatic artery up to the inferior vena cava anastomosis and underwent venoplasty three times. He also received subcutaneous injections of enoxaparin for 5 mo and 20 transfusions of blood components. Three years and ten months after the liver transplantation, transaminitis was detected with positive tests for HBs Ag, HBe Ag, and anti-HBc(2169.61, 1706 and 8.45, respectively; cutoff value: < 1.00) and an HBV viral load of 33212320 IU/mL.CONCLUSION The present study showed that loss of hepatitis B immunity after liver transplantation is unexpectedly common. In our case report, despite high levels of antiHBs prior to transplantation, infection occurred at a time when, unfortunately, the child had lost immunity to hepatitis B after liver transplantation.

Evaluation on expression of the recombinant S gene of human hepatitis B virus in vitro and in vivo

OBJECTIVES: To construct a DNA vaccine capable of expressing the S gene of hepatitis B virus (HBV)and evaluate the expression of the recombinant S gene in vitro and in vivo.METHODS: A cloned S-X gene fragment was inserted into an eukaryote expression vector to construct arecombinant expressing plasmid pCMV-SX. The recombinant plasmid was transcribed in vitro with a T7promoter transcription system and transfected into a human hepatoblastoma cell line HepG2. Theexpression of the S gene was detected by Northern blot hybridization, Western blot hybridization, andenzyme-linked immunosorbent assay (ELISA), respectively. BALB/c mice were inoculated with therecombinant plasmid, and the efficiency of DNA-based immunization in eliciting anti-HBs was evaluatedby ELISA.RESULTS: In vitro transcription of the subcloned HBV S gene was confirmed by Northern blothybridization. The results of Western blot hybridization and ELISA showed that the S gene was expressedexactly in HepG2. In immune experiment, 2 of 10 immunized mice were shown to induce antibody againstHBsAg.CONCLUSION: The recombination and expression of the S gene can be achieved successfully in vitro.And the recombinant plasmid is able to elicit humoral immune response in mice.

Seropositivity for Hepatitis B Virus, Vaccination Status and Response to Vaccine in a Cohort of Dental Students

Background: The development of a vaccine against hepatitis B virus (HBV) has been a major achievement in terms of prevention of HBV infection. To evaluate the immunological status against HBV of dental-profession students, we analysed the long-term immunogenicity and effectiveness of HBV vaccination in Italian dental students with different work seniorities, determining the influence of epidemiological variables on the immune response. Methods: This study, carried out from January 2014 to April 2016, involved 361 under- and post-graduate dental students attending the Second University of Naples. HBV serum markers were determined and multivariate logistic regression analysis was used to identify factors associated with the level of long-term immunogenicity. Results: Of the 361 subjects evaluated, 15 (4.2%) declared no history of vaccination. All vaccinated subjects were HBsAg/anti-HBc negative, with 86 (24.9%) having an anti-HBs titre <10 IU/L. The latter were younger, more likely to be attending undergraduate dental school, and more likely to have been vaccinated in infancy. Conclusion: The findings of this study suggest that assessment of HBV serum markers in workers potentially exposed to hospital infections is useful to identify small numbers of unvaccinated subjects or vaccinated subjects with low antibody titre, all of whom should be referred for a booster series of vaccinations.

Immune Response after Hepatitis B Vaccination among Egyptian Medical Students in Nile Delta

Background: Early promotion of hepatitis B (HB) vaccination among health care workers is an important component of the HBV infection control. No available data assess immune response of HB vaccination among Egyptian medical students. Objective: we conducted this study to evaluate the immune response among medical students after completion of their vaccination schedule. Methods: A total of 150 Egyptian medical students were included. Three doses of recombinant HB vaccine had been administered to all participating students at 0, 1 and 6 months. Antibody to hepatitis B surface antigen (Anti-HBs) titers, hepatitis B surface antigen (HBsAg), and total antibody to hepatitis B core antigen (anti-HBc) were measured by enzyme immunoassay, 1 to 2 months after completion of vaccination course. Results: Among 150 students included, the mean age was 22.4 ± 1.7 years (range 18 - 28 years). Fifty nine (39.4%) were males and 91 (60.6%) were females. All students have anti-HBs levels more than 100 IU/L. The mean anti-HBs of included students was 8994.2 ± 6373.1 IU/L. There was no significant difference of anti-HBs levels regarding age, sex, residence or body mass index distribution. Conclusion: Early HB vaccination of health care workers is associated with good immune response and should be encouraged.

抗—HBe阳性患者HBV—DNA,β2—MG及肝组织学改变的研究

对３２例抗－ＨＢｅ阳性患者血清的ＨＢＶ－ＤＮＡ，β－ＭＧ及肝组织学改变进行了观察，结果显示：抗－ＨＢｅ阳性患者５９％存在病毒复制，β２－ＭＧ慢活肝稍高于慢直，但全部均偏低，均有肝病理组织学改变，其中ＣＰＨ２８例（８７．５％），ＣＡＨ３例（９．４％），ＥＨＣ１例（３．１％）。指出鉴于抗－ＨＢｅ阳性患者仍有半数以上有病毒复制，免疫功能低下，全部有肝组织学损害，故其治疗难度不亚于ＨＢｅＡｇ阳性者。

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.

Vaginal Delivery and Breastfeeding Benefit Infant Immune Response to Hepatitis B Vaccine:A Prospective Cohort Study

Background and Aims:Natural vaginal delivery and breastfeeding favor the development of a strong immune system in infants,and the immune response of infants to vaccines is closely related to their immune system.This large prospective cohort study aimed to explore the effects of delivery and feeding mode on infant’s immune response to hepatitis B vaccine(HepB).Methods:A total of 1,254 infants who completed the whole course of HepB immunization and whose parents were both HBsAg negative were enrolled from infants born in Jinchang City during 2018-2019 by cluster sampling method.Results:Twenty(1.59%)of the 1,254 infants were nonresponders to HepB.Among the other 1,234 infants,10.05%(124/1,234),81.69%(1,008/1,234)and 8.27%(102/1,234)of infants had low,medium,and high responses to HepB,respectively.Logistic regression analysis showed that cesarean section(OR:8.58,95%CI:3.11-23.65,p<0.001)and birth weight<3.18 kg(OR:5.58,95%CI:1.89-16.51,p=0.002)were independent risk factors for infant nonresponse to HepB,and cesarean section(OR:7.63,95%CI:4.64-12.56,p<0.001),formula feeding(OR:4.91,95%CI:1.47-16.45,p=0.001),maternal antiHBs negativity(OR:27.2,95%CI:10.67-69.35,p<0.001),paternal non-response history of HepB(OR:7.86,95%CI:2.22-27.82,p=0.014)and birth weight<3.22 kg(OR:4.00,95%CI:2.43-6.59,p<0.001)were independent risk factors for infant low response to HepB.In cases where birth weight and genetic factors are unmodifiable and maternal anti-HBs effects are controversial,it makes sense to enhance infant response by changing delivery and feeding patterns.Conclusions:Natural vaginal delivery and breastfeeding are beneficial to the infant’s immune response to HepB.

Durability of Hepatitis B surface antigen seroclearance in patients experienced nucleoside analogs or interferon monotherapy: A real-world data from Electronic Health Record

Little is known about the difference in durability of HBsAg seroclearance induced by nucleoside analogs (NAs) or by interferon (IFN). A real-world, retrospective cohort study was conducted. Patients were assigned into two groups: NAs monotherapy-induced HBsAg seroclearance subjects and IFN monotherapy induced-HBsAg seroclearance subjects. A total of 198 subjects, comprised by 168 NAs monotherapy-induced and 30 IFN monotherapy-induced, who achieved HBsAg seroclearance were included in this study. The one-year probabilities of confirmed HBsAg seroclearance were significantly different in patients with NAs monotherapy and IFN monotherapy (0.960 (with 95% CI 0.922–0.999) vs. 0.691 (with 95% CI 0.523–0.913), log-rank-P = 4.04e-4). 73.3% (11 of 15) HBsAg recurrence occurred within one year after HBsAg seroclearance. The one-year probabilities of confirmed HBsAg seroclearance were higher in IFN monotherapy patients with anti-HBs than in IFN monotherapy patients without anti-HBs (0.839 (with 95% CI 0.657–1.000) vs. 0.489 (with 95% CI 0.251–0.953), log-rank test, P = 0.024). Our study thus provided novel insights into the durability of HBsAg seroclearance induced by NAs or IFN monotherapy. In particular, the HBsAg seroreversion rate was relatively high in IFN monotherapy subjects. The presence of anti-HBs was significantly correlated with a longer durability of functional cure induced by IFN treatment. And one-year follow-up in HBsAg seroclearance achieved individuals is proper for averting HBsAg seroreversion and other liver disease.