母系HBeAg阳性是接种乙肝疫苗失效的主要原因

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乙型肝炎病毒（HBV）感染是一项全球性的健康问题。全球目前共有20亿乙肝病毒携带者，其中有3.6亿为慢性乙型肝炎表面抗原（HBsAg）阳性携带者。乙肝发展可导致肝功能衰竭，肝硬化以及肝癌，从而带来一系列社会经济问题。目前最有效的预防乙肝的方式是婴儿期乙肝病毒疫苗接种，但其婴儿期后的免疫有效性并不是100%。有文献报道，在接种疫苗后的儿童，仍会出现慢性乙型肝炎的感染，婴儿接种乙肝疫苗后失效的机理现在还没有完全搞清楚。来自台湾新北市马偕医学院内科学的Tzu-Wei Wu（吳子維）等人进行了一项相关研究，这项研究成果在线发表在最新一期（2013 Jan）的《Hepatology》上。

这项研究的纳入研究对象是8733名在1987年7月后出生的高中学生，对其乙肝表面抗原（HBsAg）和表面抗体（anti-HBs）进行了检测。其总体HBsAg和anti-HBS的阳性率分别为1.9%和48.3%.在接受乙肝免疫球蛋白的学生中，HBsAg阳性率为15%（调整后风险比为：15.63；95%置信区间为：10.99-22.22）。在没有接受乙肝免疫球蛋白（HBIG）的学生中，其乙肝病毒疫苗剂量和乙肝表面抗原直接有明显的负相关性。（p 趋势值为0.011）。调整后的风险比在接受过4次，3次和1-2次乙肝疫苗的学生中分别是1.00, 1.52（95%置信区间 0.91-2.53）和2.85(95% CI: 1.39-5.81)。接受HBIG的学生，如果母系乙肝e抗原阳性率和接受HBIG不足，其HBsAg阳性率明显升高。

1974名HBsAg-和anti-HBs阴性的学生进行了乙肝疫苗的加强接种。比较了加强前和加强后，血中anti-HBs计数。加强疫苗后的anti-HBs滴定效价<10 mIU/mL占所有接种人数的27.9%。接种前anti-HBs在1.0-9.9IU/mL在接受加强后，其效价增强比加强前抗体滴度<1.0 mIU/mL的学生明显增多。(p<0.0001)

这项研究的结论，婴儿在产后接受主动免疫乙肝疫苗接种15年后发现HBsAg阳性青年，其最重要的决定因素为母系的HBeAg阳性。很大一部分完全免疫接种者会丧失对HBsAg的免疫记忆。

bigben446

Title: Chronic hepatitis B infection in adolescents who received primary infantile vaccination
Author: Wu, T. W.; Lin, H. H.; Wang, L. Y.
Source: Hepatology, 2013, 57(1): 37-45
Abstract:
  Hepatitis B virus (HBV) infection is a global health issue. Universal infantile hepatitis B (HB) vaccination is very efficacious. However, HBV infections among those immunized subjects have been reported. The long-term efficacy of postnatal  passive-active HB vaccination in high-risk subjects is not well explored. A total of 8,733 senior high school students who were born after July 1987 were assayed for hepatitis B surface antigen (HBsAg) and antibodies to HBsAg (anti-HBs). The overall HBsAg and anti-HBs-positive rates were 1.9% and 48.3%, respectively. The  HBsAg-positive rate was 15% in HB immunoglobulin (HBIG) recipients (adjusted odds ratio [OR]: 15.63; 95% confidence interval [CI]: 10.99-22.22). Among students who did not receive HBIG, there was a significantly negative association between HB vaccination dosage and HBsAg-positive rate (P for trend = 0.011). Adjusted ORs for those who received 4, 3, and 1 to 2 doses were 1.00, 1.52 (95% CI: 0.91-2.53), and 2.85 (95% CI: 1.39-5.81), respectively. Among HBIG recipients, the HBsAg-positive rate was significantly higher in subjects with maternal hepatitis B e antigen (HBeAg) positivity and who received HBIG off-schedule. A booster dose of HB vaccination was administered to 1974 HBsAg- and anti-HBs-negative subjects. Prebooster and a postbooster blood samples were drawn for anti-HBs quantification. The proportions of postbooster anti-HBs titer <10 mIU/mL was 27.9%. Subjects with prebooster anti-HBs titers of 1.0-9.9 mIU/mL had  significantly higher postbooster anti-HBs titers than those with prebooster anti-HBs titers of <1.0 mIU/mL (P < 0.0001). Conclusion: Having maternal HBeAg positivity is the most important determinant for HBsAg positivity in adolescents  who received postnatal passive-active HB vaccination 15 years before. A significant proportion of complete vaccinees may have lost their immunological memories against HBsAg. (HEPATOLOGY 2013).
http://onlinelibrary.wiley.com/doi/10.1002/hep.25988/abstract;jsessionid=BB4A3770B283251F48FA64BC5DB19B6F.d03t03