拉米呋定与乙肝疫苗预防HBcAb阳性供肝儿童肝移植术后新发乙肝病毒感染效果的对照研究

目的 比较拉米呋定与乙肝疫苗方案预防乙型肝炎核心抗体(hepatitis B core antibody,HBcAb)阳性供肝儿童肝移植术后新发乙型肝炎病毒(hepatitis B virus,HBV)感染效果.方法 对天津市第一中心医院自2013年5月—2019年6月251例接受HBcAb阳性供肝儿童肝移植的资料进行...     

中国人群乙型肝炎病毒表面抗原流行规律变迁的初步研究

目的 了解中国人群乙型肝炎病毒表面抗原(HBsAg)流行趋势和分布变化.方法 系统分析3次全国乙型肝炎血清流行病学调查的资料.结果 乙肝疫苗使用前后,HBsAg流行特征发生了改变,1～14岁儿童HBsAg流行率呈大幅度下降,城市儿童下降最显著.目前中国HBsAg高流行区依然集中在青藏高原、长江流域、沿海地区.结论 乙肝疫苗免疫预防接种取得了良好的效果,HBsAg高流地区应结合当地的实际情况,寻求有效的防治策略.     

湾里区15岁以下儿童乙肝感染和免疫状况调查

目的掌握湾里区15岁以下重点人群乙肝感染和免疫状况,为制定15岁以下儿童乙肝防治策略提供可靠的依据。方法采用酶联免疫法对3 128名1～15岁乙肝表面抗原携带情况进行调查分析,以问卷和查验预防接种证或卡片的方式对乙肝疫苗接种率进行调查。结果 3 128名儿童中HBsAg阳性104名,阳性率为3.32%。合格接种乙肝疫苗2 438人,接种率为77.94%。结论 HBsAg携带率随年龄增长而逐渐上升。乙肝疫苗的接种率随着年龄的增长逐渐降低。合格接种乙肝疫苗接种是阻断乙肝传播的有效途径,今后需提高乙肝疫苗的合格接种率,重点在大年龄组（6岁以上）儿童中开展乙肝疫苗查漏补种工作,加强乙肝防治知识的宣传,实现15岁以下重点人群乙肝表面抗原携带率3%以下目标。     

猪苓多糖联合乙肝疫苗治疗慢性乙型肝炎疗效观察

猪苓多糖联合乙肝疫苗对36例慢性乙型肝炎患者进行了疗效观察.猪苓多糖40mg连续20天,休息10天,重复3个月为一疗程,同时每周肌肉注射乙肝疫苗30mg,6次为一疗程.治疗后ALT复常率88.46％.HBeAg转阴率为55.55％,明显优于对照组,在改善症状及肝功能方面亦较对照组为优.猪苓多糖联合乙肝疫苗治疗慢性肝炎可纠正慢性肝炎免疫功能失调,增加抗病能力,值得推广应用..     

5岁以下儿童肝移植术后注射乙肝疫苗免疫效果的多因素分析

目的探讨5岁以下儿童肝移植术后接种乙肝疫苗免疫应答的效果及多针次接种必要性的评估。方法回顾性分析2014年2月—2018年12月于首都医科大学附属北京友谊医院普外科同一肝移植组进行肝移植手术,术后遵医嘱注射乙肝疫苗完成4针次以上的5岁以下170例患儿的临床资料,其中男性75例,女性95例,年龄4个月至5岁,患儿每针次接种疫苗后随来院肝移植门诊复诊时抽血检测乙肝五项,观察HBsAb应答效果及其相关影响因素。计数资料数据用例数和百分数(%)表示,组间比较用χ^2检验。结果5岁以下患儿肝移植术后完成第1个疗程乙肝疫苗注射后免疫应答成功121例(HBsAb≥100 IU/L),应答失败49例(HBsAb<100 IU/L),接种第2个疗程后应答成功29例,最终只有20例患儿接种8针次即2个疗程后HBsAb<10 IU/L。影响乙肝疫苗接种免疫效果的相关因素与性别、原发病、供肝方式、术后接种疫苗时间无关,与年龄、居住地、术前HBsAb滴度高低有关(抗-HBs以100 IU/L为标准)。平均年龄2岁以上患儿明显比1岁以下患儿术后接种第1个疗程后免疫应答率高,术前儿童接种过乙肝疫苗且抗-HBs滴度>100 IU/L患儿其术后接种第1疗程后免疫应答率更高(84.72%),术前抗-HBs滴度<100 IU/L患儿术后接种乙肝疫苗第1疗程后免疫应答稍低(60.71%)。结论大部分肝移植患儿可通过接种乙肝疫苗主动免疫获得保护性抗体来预防乙肝病毒再感染,坚持多针次接种能有效地诱导机体产生乙肝抗体,提高免疫应答水平,具有保护效果,且经济有效,肝移植术后接种乙肝疫苗存在必要性,是目前肝移植术后推广应用方法之一。     

磁微粒化学发光法定量检测525名儿童表面抗体结果分析

目的:简要了解我市儿童乙型肝炎(下称乙肝)病毒表面抗体的浓度,以观察该群体抵御乙肝痛毒侵入的能力.方法:以磁徽粒化学发光免疫分析仪定量检测525名儿童的乙肝病毒表面抗体(HBsAb)浓度,然后对所有结果进行统计分析.结果:在525名儿童中,乙肝病毒表面抗体(HBsAb)浓度值≤10mIU/ml 126人,完全不具有抵御乙肝病毒(HBV)入侵的能力,需要立即进行乙肝疫苗的接种;HBsAb浓度值在10-100mIU/m1 150人,具有部分抵御HBV入侵的能力,需要进行乙肝疫苗加强接种;HBsAb浓度值≥100mIU/ml 249人,具有抵御HBV入侵的能力,不需要进行乙肝疫苗接种.结论:许多儿童不具有和不完全具有抵御HBV入侵的能力,需要进行乙肝疫苗接种,以预防乙肝.     

60ug乙肝疫苗对无应答人群免疫效果观察

目的:评价60ug乙肝疫苗应用于常规乙肝疫苗无应答人群的免疫效果.方法:对2012年7月在我院体检中心体检的电信局、移动公司、海事局三个单位中1 08名血清中的HBsAg、抗-HBs、HBeAg、抗-HBe及抗-HBc均为阴性,以往接种常规乙肝疫苗无应答人群接种60ug乙肝疫苗,1月后检测血清抗-HBs指标.结果:接种后抗-HBs阳转率为86.11％;抗-HBs GMT(95％CI)为122.103(101.364-149.653).结论:60ug乙肝疫苗在受试人群中具有良好的免疫原性.建议对乙肝疫苗常规免疫无应答人群和不能按要求程序全程接种三针常规乙肝疫苗人群,接种60ug乙肝疫苗.     

乙型肝炎疫苗成人免疫策略的研究进展

乙型肝炎是影响人类健康的重要公共卫生问题,根据世界卫生组织(WHO)统计,全世界大约有20亿人感染或曾经感染过HBV,主要来自亚洲、非洲及拉丁美洲等发展中国家,其中约3.5亿为HBV慢性感染者,每年死于乙型肝炎的患者约有100万人[1].我国乙型肝炎流行率较高,据调查显示[2],我国每年因治疗HBV感染所花费的金额高达6000亿元,这给国家和人民带来沉重的负担,而注射乙型肝炎疫苗是预防乙型肝炎最实用也是最有效的方法.2002年我国开始实施新生儿免费接种乙型肝炎疫苗,经过数十年的不懈努力,我国适龄儿童乙型肝炎表面抗原(HBsAg)携带者减少了约2000万[3],这也说明了儿童乙型肝炎疫苗接种的必要性和重要性,但考虑到我国具体国情,普遍让成人接种乙型肝炎疫苗还不能实现.因此,研究乙型肝炎疫苗成人的免疫策略,提高免疫接种成功率,是今后乙型肝炎预防工作的热点.本文就近年来乙型肝炎疫苗成人免疫策略的研究进展作一综述,希望能为成人乙型肝炎预防研究提供参考.     

胸腺肽a1改善血液透析患者乙型肝炎疫苗免疫应答的临床研究

目的:维持性血液透析(Hemodi al ysi s,MHD)患者为乙型肝炎病毒(Hepat i t i sB Vi rus,HBV)感染的高危人群,改善其对乙型肝炎疫苗的免疫应答有重要的临床意义,而通过临床发现,相当多的MHD患者对常规乙型肝炎疫苗的应答差,血清转换率低下。本研究探讨了对MHD患者应用胸腺肽a1改善其对乙型肝炎疫苗免疫应答的效果。方法:采用多中心、随机的方法,将79例具备正常转氨酶水平、HBsAg(-)、Ant i-HBc(-)及Ant i-HBs(-)的MHD患者随机分为两组,A组MHD患者39例,进行常规疗程(O月、1月、6月)肌内注射普通基因重组乙肝疫苗,10μg/针,每次注射剂量为2针20μg,共三次6针,总剂量为60μg;B组MHD患者40例,按A组方法行乙肝疫苗接种,随后行胸腺肽a1皮下注射,每次1.6mg,每周2次,连续用4周(共8针),第一针在疫苗注射后立即皮下注射。以乙肝表面抗体滴度≥10 ml U/ml为产生保护性血清转换。注射结束后3个月检测乙肝表面抗体滴度,分析两组之间保护性血清转换率及抗体滴度水平的差异。结果:A组患者有26例产生了保护性抗体,保护性血清转换率为66.67%,B组患者有37例产生了保护性抗体,保护性血清转换率为92.50%,两组差异有统计学意义(P<0.01);同时B组的抗体滴度明显高于A组,两组差异有统计学意义(P<0.01)。两组患者抗体滴度水平与患者性别、年龄、病程、肌酐水平、白蛋白水平、血红蛋白水平等无明显相关性(P>0.05)。结论:MHD患者对常规基因重组乙肝疫苗的免疫应答低下,胸腺肽a1可明显改善MHD患者的免疫应答,增强乙肝疫苗的免疫效果,故可减少MHD患者感染乙肝的概率,改善其生存质量。     

专科学校乙型肝炎普查结果分析

目的了解专科学校学生乙型肝炎的流行情况,为制订预防对策提供科学依据。方法采用酶联免疫吸附法检 测5届在校生2353人乙型肝炎4项指标,并进行对比研究。结果HBsAg阳性率及抗 HBc阳性率逐年降低、疫苗 的接种率和抗 HBs阳性率逐年升高;城市学生疫苗接种率及抗 HBs阳性率较农村学生高(均P<0.01),HBsAg 阳性率及抗 HBc阳性率较低(均P<0.01)。结论重视青少年乙肝疫苗接种工作,加强其免疫作用,定期复查,及 时了解体内抗体的效价,并加以防范是阻止乙型肝炎在校内流行的有效措施。     

Hepatitis B surface antigenemia following recombinant Engerix B hepatitis B vaccine in an 81-year-old ESRD patient on hemodialysis

The first cases of transient hepatitis B surface antigenemia (HBsAg) in adults following hepatitis B virus (HBV) immunization were reported in the 1990s. HBV immunization is mandatory for all hemodialysis (HD) patients. Ly et al. who demonstrated transient HBsAg in eight out of nine HD patients following HBV vaccine concluded that HD patients should not be screened for HBV within a week of HBV immunization and that positive HBsAg within a month of HBV immunization must be interpreted with caution. We present an 81-year-old woman on HD, who needed a booster Recombivax (Merck, Whitehouse Station, NJ, USA) vaccine after remaining hepatitis B surface antibody (HBsAb) negative from previous vaccinations. The HD Unit had switched to Engerix B (GlaxoSmithKline, Atlanta, GA, USA) HBV vaccine. Two days after the first Engerix B vaccine, HBsAg was detected. She was asymptomatic; ALT was 25 U/L. Repeat testing for HBsAg, HBsAb, hepatitis B E antigen (HB E Ag), and hepatitis B DNA (HB DNA), a week later, all returned negative. Previous reports of transient HBsAg following HBV vaccines were after Engerix B vaccination. Our patient is unusual since she had received both brands of HBV vaccines, sequentially, at different times. Twice, HBsAg tests completed as early as 5 days following Recombivax vaccine were negative. We submit that positive HBsAg tests are more likely following Engerix B vaccines. We reemphasize previous recommendations that patients should not be screened for HBsAg < 4 weeks following HBV immunization. This is particularly important in HD units where hepatitis B screening is carried out routinely all year round and hepatitis B vaccinations are commonplace. Very strict schedules must be adopted to avoid false positive HBsAg tests.     

Vaccinations for adult solid organ transplant recipient: current recommendations

The need for immunization in solid organ transplant recipient can arise from three factors: immune deficit owing to underlying disease, rejection of the organ graft, and immunosuppressive therapy given after transplantation. As a general rule, primary immunizations should be given as early as possible before transplantation because the immune response to vaccines is decreased in patients with end-stage organ disease. There are three categories of vaccines: Live vaccines--oral polio, vaccinia, bacillus Calmette-Guerin, live oral typho?d, and intranasal influenza vaccines--are contraindicated in solid organ transplant recipients. The use of varicella vaccine remains controversial. The use of rubella vaccine is recommended in young women of childbearing age. Of the killed vaccines or genetically engineered vaccines, the following are recommended: pneumococcal vaccine, influenza vaccine, hepatitis A vaccine, hepatitis B vaccine, diphtheria, and tetanus vaccine. Vaccination of household contacts and health care workers in transplant centers is recommended. However, live vaccine (with the exception of varicella vaccine) should be avoided in these contacts.     

Granulocyte-macrophage colony-stimulating factor as an adjuvant to hepatitis B vaccination in maintenance hemodialysis patients

Patients on maintenance hemodialysis (HD) have poor seroconversion rate after hepatitis B vaccination. The present study was designed to test the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as an adjuvant to hepatitis B vaccination for improving seroconversion rate in maintenance HD patients. Twelve chronic HD patients were randomly assigned to receive either hepatitis B vaccination alone or hepatitis B vaccination 24 h after 1 dose of GM-CSF for primary immunization. A group of 16 chronic HD patients who had not seroconverted after a standard two-dose hepatitis B vaccination were randomly assigned either to a booster dose of hepatitis B vaccine alone or a booster dose given 24 h after one dose of GM-CSF. In the primary immunization group only 2 of 6 patients (33%) who had received vaccination alone, versus 5 of 6 patients (83%) who had received hepatitis B vaccine after one dose of GM-CSF, developed seroprotective antibody titers. Moreover, seroprotective antibody titers (IU/ml) were significantly higher in the latter group (275 +/- 286.5 vs. 14 +/- 22, p < 0.05). In patients who had not seroconverted with prior hepatitis B vaccination, GM-CSF adjuvant therapy significantly increased the seroconversion rate versus booster dose alone (87.5 vs. 25%, respectively, p < 0.02), with significantly higher seroprotective antibody titers (84 +/- 80 vs. 19 +/- 33 IU/ml, respectively, p < 0. 05). These findings suggest that administration of one dose of GM-CSF, as adjuvant therapy, prior to primary or booster dose hepatitis B vaccination may significantly increase seroconversion rate and seroprotective antibody titers in chronic HD patients.     

The extrahepatic manifestations of hepatitis B virus

Hepatitis B Virus (HBV) leads to a number of hepatic complications, from acute to chronic hepatitis, cirrhosis and hepatocellular carcinoma, is a well-established fact. Upcoming clinical research, over the years, associates numerous extrahepatic manifestations during the acute and chronic episodes of hepatitis B with significant morbidity and mortality. A causal relationship between HBV and serious autoimmune disorders has also been observed among certain susceptible vaccine recipients in a defined temporal period following immunization. The cause of these extrahepatic manifestations is generally believed to be immune mediated. The most commonly described include skin rash, arthritis, arthralgia, glomerulonephritis, polyarteritis nodosa, and papular acrodermatitis etc. The serum-sickness like "arthritis-dermatitis" prodrome has also been observed in approximately one-third of patients acquiring HBV infections. Skin manifestations of HBV infection typically present as palpable purpura reported to be caused by chronic HBV, although this association remains controversial. To consider the relationship between HBV and other clinically significant disorders as well as serious autoimmune disorders among certain vaccine recipients is the topic of this review. Variable factors that influence extrahepatic manifestation are discussed, including possible synergy between hepatitis B virus and the immune system.     

Successful hepatitis B vaccination in liver transplant recipients with donor-specific hyporesponsiveness

Currently, patients are prescribed lifelong treatment with hepatitis B immunoglobulin (HBIg) after liver transplantation (LT) for hepatitis B virus (HBV)-related diseases in order to prevent reinfection with HBV. Active immunization with an HBV vaccine would be a preferable alternative; however, the immunosuppressive environment in LT recipients is believed to elicit a poor response to vaccination. Minimizing the exposure of the HBV-infected LT recipients to immunosuppressants would be beneficial in inducing adaptive immunity against HBV by vaccination. In this study, in addition to efforts to minimize immunosuppression, prophylaxis with HBV vaccination combined with continuous HBIg administration was performed in 17 LT recipients who had undergone transplantation attributable to HBV-related diseases. During the observation period, the overall response rate to HBV vaccination was 64.7%. The immune status of the recipients was evaluated by a mixed lymphocyte reaction assay in response to allostimulation. Patients showing a donor-specific hyporesponse with a well-maintained response to the third-party stimulus always achieved a sustained immune response to the vaccine, whereas patients showing a hyporesponse to both the donor and the third-party stimulus were unable to do so. Thus, inducing an anti-donor-specific immunosuppressive status by minimizing immunosuppression should enable post-transplant HBV vaccination to be a promising prophylactic strategy.     

Usefulness of a systematic approach at listing for vaccine prevention in solid organ transplant candidates

Solid organ transplant (SOT) candidates may not be immune against potentially vaccine‐preventable diseases because of insufficient immunizations and/or limited vaccine responses. We evaluated the impact on vaccine immunity at transplant of a systematic vaccinology workup at listing that included (1) pneumococcal with and without influenza immunization, (2) serology‐based vaccine recommendations against measles, varicella, hepatitis B virus, hepatitis A virus, and tetanus, and (3) the documentation of vaccines and serology tests in a national electronic immunization registry ( www.myvaccines.ch ). Among 219 SOT candidates assessed between January 2014 and November 2015, 54 patients were transplanted during the study. Between listing and transplant, catch‐up immunizations increased the patients’ immunity from 70% to 87% (hepatitis A virus, P = .008), from 22% to 41% (hepatitis B virus, P = .008), from 77% to 91% (tetanus, P = .03), and from 78% to 98% (Streptococcus pneumoniae, P = .002). Their immunity at transplant was significantly higher against S. pneumoniae (P = .006) and slightly higher against hepatitis A virus (P = .07), but not against hepatitis B virus, than that of 65 SOT recipients transplanted in 2013. This demonstrates the value of a systematic multimodal serology‐based approach of immunizations of SOT candidates at listing and the need for optimized strategies to increase their hepatitis B virus vaccine responses.     

Vaccination against hepatitis B in liver transplant recipients: pilot analysis of cellular immune response shows evidence of HBsAg-specific regulatory T cells.

After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4(+) T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4(+)/CD25(+) phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (T(Reg)). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific T(Reg) cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of T(Reg) cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on T(Reg) cells would be desirable.     

Vaccination against hepatitis B in children and adolescent patients on dialysis

Twenty-one children and adolescent patients, 2-19 years of age, on renal replacement therapy were immunised at monthly intervals with three doses of 20 micrograms hepatitis B vaccine (Heptavax B, Merck Sharp & Dohme). In the absence of seroconversion, vaccination was continued with monthly doses of 40 micrograms hepatitis B vaccine until antibody to hepatitis B surface antigen became positive. The rate of seroconversion increased from 33.3% (7 of 21) to 76.1% (16 of 21) and 85.6% (18 of 21) with three, four and five vaccine injections respectively. Three patients had no immune response despite six to seven vaccine dosages; they had previously received immunosuppressive therapy. Antibody titres measured 1 year after seroconversion were found to be within the protective range (85-2500 mIU/ml). These results show that the impaired immune response to hepatitis B vaccination in young dialysis patients can be overcome by increasing the number of injections and the dose of the vaccine. Protective antibody titres are maintained for at least 1 year after vaccination. Immunosuppressive therapy may interfere with the vaccine response.     

Reinforced intradermal hepatitis B vaccination in hemodialysis patients is superior in antibody response to intramuscular or subcutaneous vaccination

Since 1960, hepatitis B virus-associated chronic liver disease has been considered an important problem in dialysis units in both Europe and North America. Separate dialysis facilities for hepatitis B-infected patients, the implementation of universal precautions for the prevention of transmission, and the active immunization against hepatitis B have now reduced the yearly incidence to less than 0.05% in Western countries. However, only 50% to 60% of patients with renal insufficiency develop sufficient immune response after intramuscular hepatitis B vaccination. The aim of the current study was to determine whether the mode of vaccine application plays a role in vaccination response and whether increasing the vaccine dose of primary intradermal hepatitis B vaccination can reduce the number of vaccine injections in hemodialysis patients. We designed a prospective, randomized study of antibody responses to hepatitis B vaccine given intradermally, subcutaneously, or intramuscularly in 81 hemodialysis patients. Outcome measures were rates of seroconversion, mean levels of anti-Hbs antibodies, and antibody levels 8 years after vaccination. The results show that intradermal hepatitis B vaccination response with a higher vaccination dose than previously used in hemodialysis patients is superior to conventional intramuscular and subcutaneous vaccination and is also well tolerated. Five intradermal injections of 20 microg each induced the development of sufficient anti-Hbs antibody titer, which persisted in 70% of the patients over 3 years.