慢性血吸虫病对乙型肝炎疫苗保护性免疫的影响

目的 研究慢性血吸虫病患者对乙型肝炎（乙肝）疫苗保护性免疫的影响。 方法 随机筛选无乙肝病毒感染的慢性血吸虫病患者（实验组）24例,健康志愿者（对照组）26例。分别收集实验组和对照组接种乙肝疫苗前后血清,用ELISA法检测两组接种前后血清乙肝病毒表面抗体（抗-HBs）、肿瘤坏死因子-α（TNF-α）及白细胞介素-2（IL-2）的水平。 结果 接种乙肝疫苗前实验组和对照组抗-HBs平均吸光度（A值）分别为0.134和0.150。接种后,实验组血清抗-Hbs 平均A值为0.217, 转阳率为17%,与接种前相比差异无统计学意义（P > 0.05);对照组抗-Hbs平均A值为1.210, 转阳率为92%,与接种前相比差异有显著的统计学意义（P < 0.01）。 实验组接种乙肝疫苗前血清IL-2和TNF-α平均水平均明显高于对照组,接种后两组血清IL-2和TNF-α平均水平均升高,但与接种前相比差异无统计学意义（P >0.05)。 结论 慢性血吸虫病患者对乙肝疫苗的免疫应答水平低下。     

HBV基因型和S基因序列特点与慢性乙型肝炎患者HBsAg/抗-HBs共存关系

目的探讨HBV基因型及S基因序列特点与慢性乙型肝炎（CHB）患者HBsAg和抗-HBs共存的内在相关性以及HBsAg＋/抗-HBs＋的发生机制及意义。方法共收集49例HBsAg＋/抗-HBs＋CHB患者的血清HBVDNA样本,采用PCR-RFLP及测序法鉴定其基因型,并与267例HBsAg＋/抗-HBs-CHB患者的HBV基因型分布进行比较。对6例HBsAg＋/抗-HBs＋CHB患者（Ⅰ组）的HBVS基因进行克隆测序,并与HBsAg＋/抗-HBs-CHB患者（Ⅱ组）进行对比,分析变异种类及频率等的差异。结果 HBsAg＋/抗-HBs＋CHB患者HBV基因型B、C及B/C混合感染的构成比分别为63.3%（31/49）、26.5%（13/49）、10.2%（5/49）,而对照组上述构成比分别为52.8%（141/267）、46.1%（123/267）、1.1%（3/267）,两组构成比差异有统计学意义（P〈0.01）。Ⅰ组HBsAg各区段,特别是主要亲水区（MHR）的变异位点明显多于Ⅱ组;发现了若干新变异、少见的W196和C69终止突变,1例患者检测到G145R变异。某些患者HBsAgMHR-2（包含a决定簇）并未发现变异。结论 HBV基因型的差异及HBsAg变异增多可能是部分CHB患者出现HBsAg＋/抗-HBs＋的原因之一;基因型B或B/C混合感染相对更易出现HBsAg＋/抗-HBs＋。HBsAg变异增多是CHB患者出现HBsAg＋/抗-HBs＋的重要机制之一。某些患者HBsAgMHR-2并无变异,提示HBsAg/抗-HBs共存还存在其他机制。     

Cost-effectiveness of hepatitis B vaccination using HEPLISAV™ in selected adult populations compared to Engerix-B vaccine

Objective

HEPLISAV™ is an adult hepatitis B vaccine that requires fewer doses over a shorter period of time and elicits higher and earlier seroprotection compared to Engerix-B to reduce the risk of hepatitis B infection. The objective of this analysis was to evaluate the cost-effectiveness of vaccination with HEPLISAV vs. Engerix-B^® to prevent hepatitis B infection in select populations.

Methods

Markov models were developed for the following populations: diabetics, patients with chronic or end stage kidney disease, healthcare workers and international travelers to countries with high HBV infection prevalence. Hepatitis B disease progression was modeled using 11 health states: seroprotected, susceptible, acute infection, chronic infection, fulminant hepatic failure, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-transplant care, and death. Seroprotection rates were obtained from two phase 3 clinical trials comparing HEPLISAV with Engerix-B and ranged across various populations from 89–96% for HEPLISAV and 62–81% for Engerix-B. Higher vaccination completion rates were assumed for HEPLISAV compared with Engerix-B given that fewer doses of HEPLISAV are required in a shorter period of time to achieve seroprotection for the evaluated populations. Each cycle length after the first year in the model was 1-year. All future costs and benefits were discounted at 3%. A lifetime analysis and a U.S. payer perspective were used.

Results

HEPLISAV has a favorable cost-effectiveness profile with incremental cost effectiveness ratios <$25,000 across all populations studied. In the patients with chronic or end stage kidney disease, HEPLISAV was the dominant option and was cost-saving compared with Engerix-B. The cost of vaccine, regimen completion rates, and seroprotection rates were the sensitive variables in the models.

Conclusions

HEPLISAV is a cost-effective option to provide high rates of seroprotection and early seroprotection across a range of populations from health care workers to patients with chronic or end stage kidney disease.     

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4 000 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。     

乙肝基因重组疫苗两种免疫程序接种新生儿3年免疫效果观察

为了解国产乙肝基因重组疫苗免疫效果,我们分别按０、１、２月和０、１、６月免疫程序对７０名新生儿进行了３年免疫效果观察,结果发现有一人次低热（３７．８℃）,发热率为０．４８％。其余未见过敏、高热、局部红肿等副反应。新生儿分别按两种免疫程序接种后抗－ＨＢｓ阳转率在３、７、１２、２４、３６月时检测均无显著性差异（Ｐ＞０．０５）。而抗－ＨＢｓ几何平均滴度（ＧＭＴ）在３个月时０、１、２月免疫组（８１．３５）显著高于０、１、６月免疫组（３３．１４）,Ｐ＜０．０１,并发现两组免疫程序接种后,７个月左右时抗－ＨＢｓ的ＧＭＴ均达到最高峰,随访到３６个月时抗－ＨＢｓ阳转率和ＧＭＴ仍保持较高水平,且两组间无显著性差异（Ｐ＞０．０５）。说明,两种免疫程序对新生儿抗－ＨＢｓ阳转率和ＧＭＴ的诱导无显著性差异,且０、１、２免疫程序接种时间短,抗体滴度上升快。但需进一步深入研究。     

玛纳斯县学龄前儿童乙肝表面抗体水平及表面抗原携带状况调查分析

目的:调查玛纳斯县学龄前儿童抗-HBs水平和HBsAg携带状况,为预防乙肝提供依据。方法:采用分层随机抽样法在全县12个乡镇和城区随机抽取被调查对象并采血检测分析。结果:被调查510名学龄前儿童抗-HBs阳性率为72.75%。各年龄组抗-HBs阳性率在62.71%～89.01%之间,且随年龄组增长呈下降趋势(χ2=20.23,P<0.01),城区高于乡镇,乡镇高于农牧村,汉族高于少数民族,男女性别间差别无统计学意义。在510名儿童中检出HBsAg阳性10人,携带率为1.96%,维持在较低水平,地区、族别和性别间差别均无统计学意义。结论:学龄前儿童抗-HBs水平不甚理想,需继续加强乙肝疫苗接种管理工作,尤其要加强基层保健网资金投入和计划免疫接种工作。     

Fatal Hepatitis B Reactivation Treated With Entecavir in an Isolated Anti-HBs Positive Lymphoma Patient: A Case Report and Literature Review

Hepatitis B virus (HBV) reactivation is a well-recognized complication that occurs in lymphoma patients who undergo chemotherapy. Only very few cases of HBV reactivation in patients with isolated antibody against hepatitis B surface antigen (anti-HBs) have been reported. We present a case of a 78-year-old woman diagnosed with diffuse large B cell non-Hodgkin''s lymphoma who only displayed a positive anti-HBs, as the single possible marker of occult HBV infection, before starting therapy. She was treated with several chemotherapeutic regimens (including rituximab) for disease relapses during 3 years. Forty days after the last cycle of chemotherapy, she presented with jaundice, markedly elevated serum aminotransferase levels, and coagulopathy. HBV serology showed positivity for HBsAg, anti-HBc and anti-HBs. HBV DNA was positive. Antiviral treatment with entecavir was promptly initiated, but the patient died from liver failure. A review of the literature of HBV reactivation in patients with detectable anti-HBs levels is discussed.     

中国和美国三种乙型肝炎疫苗的免疫原性及安全性比较

免疫对象300人双盲随机分组,分别接种中、美三种乙型肝炎疫苗。二次接种后的结果:三种疫苗接种后反应均轻微,安全性好。初次及第二次接种后,中国血源疫苗抗HBs的阳转率为42.2%和64.0%,美国Merck基因疫苗为49.5%和86.7%,Merck血源疫苗为53.0%和77.8%。中国血源疫苗的抗体水平P/N值在50以下而Merke二种疫苗超过50以上。