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隐匿性乙型肝炎病毒和表面抗原突变感染在健康接种人群以及各种形式肝炎和多次输血的儿童中。

Occult hepatitis B virus and surface antigen mutant infection in healthy vaccinated cohorts and children with various forms of hepatitis and multiple transfusions.

机构信息

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Liver Int. 2019 Jun;39(6):1052-1061. doi: 10.1111/liv.14076. Epub 2019 Mar 8.

Abstract

BACKGROUND AND AIMS

Despite the success of universal infant immunization initiated in Taiwan in 1984, occult hepatitis B virus infection (OBI) and circulating surface antigen mutants remain potential obstacles for eventual eradication of HBV infection.

METHODS

From 3299 apparently healthy, neonatally-vaccinated subjects (<30 years of age ) enrolled during 2014 serosurvey, we recruited all HBsAg-positive (n = 17), all HBsAg-negative but anti-HBc-positive (n = 132) and randomly selected HBsAg-negative and anti-HBc-negative subjects (n = 411). These recruited subjects and 81 HBsAg-negative children with various forms of hepatitis and multiple transfusions were analysed for serum HBV DNA.

RESULTS

In healthy, HBsAg-negative subjects, OBI frequency was higher in anti-HBc-positive than anti-HBc-negative individuals (8/90[8.9%] vs 8/301[2.7%], P = 0.0192) aged <18-years, but was not different between anti-HBc-positive and anti-HBc-negative individuals (0/11[0%] vs 3/110[2.7%], P > 0.05) aged 18 to 30 years. OBI occurred more frequently in children of HBsAg-positive mothers than in children of HBsAg-negative mothers (10/101 [9.9%] vs 1/75 [1.3%], P = 0.025). The prevalence of surface 'a' determinant (aa110-160) mutants was 13.3% (2/15) in OBI subjects compared to 36.4% (4/11) in HBsAg-positive subjects (P > 0.05). OBI was found in 30% (3/10) of serologic 'non-A to E' viral hepatitis, 14.3% (3/21) of chronic hepatitis C and 2.0% (1/50) of multitransfused, thalassemic children.

CONCLUSIONS

In this highly immunized population, surface antigen mutant infection is uncommon and has low contribution to OBI development. HBsAg screening plus highly sensitive HBV DNA assays are needed for assurance of blood supply safety. Multiple transfusions from HBsAg-negative blood donors rarely result in persistent HBV infection. HBV might be related to some of serologic 'non-A to E' viral hepatitis.

摘要

背景和目的

尽管 1984 年台湾开始实施普遍婴儿免疫计划取得了成功,但隐匿性乙型肝炎病毒感染(OBI)和循环表面抗原突变体仍然是最终消除乙型肝炎病毒感染的潜在障碍。

方法

我们从 2014 年血清学调查中招募的 3299 名明显健康、新生儿接种疫苗的受试者(<30 岁)中,招募了所有 HBsAg 阳性(n=17)、所有 HBsAg 阴性但抗-HBc 阳性(n=132)和随机选择的 HBsAg 阴性和抗-HBc 阴性受试者(n=411)。对这些招募的受试者和 81 名患有各种类型肝炎和多次输血的 HBsAg 阴性儿童进行血清 HBV DNA 分析。

结果

在健康的 HBsAg 阴性受试者中,抗-HBc 阳性者的 OBI 频率高于抗-HBc 阴性者(<18 岁:8/90[8.9%] vs 8/301[2.7%],P=0.0192),但在 18 至 30 岁的抗-HBc 阳性者和抗-HBc 阴性者之间无差异(0/11[0%] vs 3/110[2.7%],P>0.05)。HBsAg 阳性母亲的儿童中 OBI 的发生率高于 HBsAg 阴性母亲的儿童(10/101 [9.9%] vs 1/75 [1.3%],P=0.025)。OBI 受试者中表面“a”决定簇(aa110-160)突变体的患病率为 13.3%(2/15),而 HBsAg 阳性受试者中为 36.4%(4/11)(P>0.05)。在 30%(3/10)的血清学“非 A 至 E”病毒性肝炎、14.3%(3/21)的慢性丙型肝炎和 2.0%(1/50)的多次输血、地中海贫血儿童中发现了 OBI。

结论

在这个高度免疫的人群中,表面抗原突变体感染并不常见,对 OBI 的发展贡献较低。需要进行 HBsAg 筛查和高度敏感的 HBV DNA 检测,以确保血液供应安全。来自 HBsAg 阴性献血者的多次输血很少导致持续性乙型肝炎病毒感染。HBV 可能与一些血清学“非 A 至 E”病毒性肝炎有关。

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