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出生时接种疫苗的女性同胞中感染携带新型前S/S基因突变的乙型肝炎病毒:两例报告

Infection with hepatitis B virus carrying novel pre-S/S gene mutations in female siblings vaccinated at birth: two case reports.

作者信息

Lai Ming-Wei, Yeh Christopher S-H, Yeh Chau-Ting

机构信息

Graduate Institute of Clinical Medical Science, Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

J Med Case Rep. 2010 Jun 23;4:190. doi: 10.1186/1752-1947-4-190.

Abstract

INTRODUCTION

After the initiation of a mass hepatitis B vaccination program in Taiwan, the prevalence of hepatitis B virus infection has declined progressively. However, about 1 percent of the young generation, who received hepatitis B vaccination at birth, remain carriers. Infection with vaccine-escape hepatitis B virus mutants always occurs shortly after birth. Here, we report two female siblings in whom the infection occurred in their adolescence. This report raises the question of whether a booster for hepatitis B vaccination is needed.

CASE PRESENTATION

Two 19 and 14-year-old Taiwanese female siblings were born to a mother infected with hepatitis B virus and received a complete course of hepatitis B vaccination at birth. They remained negative for serum hepatitis B surface antigen and positive for serum anti-hepatitis B surface antibody throughout their childhood. However, both were infected with the hepatitis B virus in their adolescence. Hepatitis B virus DNA was extracted from serum samples from the mother and two siblings. Hepatitis B virus pre-S/S sequence was amplified by polymerase chain reaction followed by nucleotide sequencing. When compared with the sequence obtained from the mother, multiple amino acid substitutions located near or in the major hydrophilic region of the surface antigen were identified in the elder sister. Four of these mutations (sL97S, sL98S, sG102R, and sA159P) were novel. A novel in-frame deletion (14 amino acids deleted, pre-S 127-140) was found in the hepatitis B virus pre-S2 region in the younger sister.

CONCLUSIONS

Despite having received hepatitis B vaccination at birth, hepatitis B virus infection can still occur in adolescence with the emergence of novel mutations in the pre-S/S gene. This is a rare event and, to the best of our knowledge, has not been previously reported.

摘要

引言

台湾启动大规模乙肝疫苗接种计划后,乙肝病毒感染率逐渐下降。然而,约1%在出生时接种过乙肝疫苗的年轻一代仍为携带者。疫苗逃逸型乙肝病毒突变体感染通常在出生后不久发生。在此,我们报告两名女性同胞在青春期感染乙肝病毒的病例。本报告提出了是否需要加强乙肝疫苗接种的问题。

病例介绍

两名分别为19岁和14岁的台湾女性同胞,其母亲感染乙肝病毒,她们在出生时接受了完整疗程的乙肝疫苗接种。在整个童年时期,她们的血清乙肝表面抗原均为阴性,血清乙肝表面抗体为阳性。然而,两人在青春期均感染了乙肝病毒。从母亲和两名同胞的血清样本中提取乙肝病毒DNA。通过聚合酶链反应扩增乙肝病毒前S/S序列,随后进行核苷酸测序。与从母亲那里获得的序列相比,在姐姐的表面抗原主要亲水区域附近或内部发现了多个氨基酸替换。其中四个突变(sL97S、sL98S、sG102R和sA159P)是新发现的。在妹妹的乙肝病毒前S2区域发现了一个新的框内缺失(缺失14个氨基酸,前S 127-140)。

结论

尽管在出生时接种了乙肝疫苗,但随着前S/S基因出现新的突变,青春期仍可能发生乙肝病毒感染。这是一个罕见事件,据我们所知,此前尚未有过报道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/190a/2904790/db4d05facf06/1752-1947-4-190-1.jpg

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