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  • 谢震宇,费怡,杨天,殷建华,蒲蕊.乙型肝炎表面抗原阳性学生及其一级亲属乙型肝炎病毒感染流行病学调查与病毒变异分析[J].第二军医大学学报,2019,40(1):54-60    [点击复制]
  • XIE Zhen-yu,FEI Yi,YANG Tian,YIN Jian-hua,PU Rui.Epidemiological investigation of hepatitis B virus infection and analysis of virus mutations in hepatitis B surface antigen positive students and their frst-degree relatives[J].Acad J Sec Mil Med Univ,2019,40(1):54-60   [点击复制]
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乙型肝炎表面抗原阳性学生及其一级亲属乙型肝炎病毒感染流行病学调查与病毒变异分析
谢震宇1*,费怡2,杨天2,殷建华3,蒲蕊3
0
(1. 上海市浦东新区妇幼保健院预防保健科, 上海 201206;
2. 上海市浦东新区疾病预防控制中心免疫预防科, 上海 200136;
3. 海军军医大学(第二军医大学)热带医学与公共卫生学系流行病学教研室, 上海 200433
*通信作者)
摘要:
目的 探讨乙型肝炎表面抗原(HBsAg)阳性学生家庭内乙型肝炎病毒(HBV)感染状况以及肝细胞癌相关的HBV变异情况,为HBV感染、肝细胞癌的防控提供科学依据。方法 从浦东新区15个学校及幼儿园60个班级中调查学生1 611名,其中HBsAg阳性学生8名。对该8名学生及其18名一级亲属进行流行病学调查,采集静脉血应用酶联免疫吸附实验检测乙肝五项。采用荧光PCR法检测HBV DNA,采用multiplex-PCR、巢式PCR法联合克隆测序方法检测HBV基因组、基本核心启动子(BCP)区和前S(PreS)区。结果 一级亲属HBsAg与HBcAb阳性率分别为33.3%(6/18)与38.9%(7/18)。母亲HBsAg与HBcAb阳性率均为71.4%(5/7),高于其他一级亲属阳性率(P<0.05)。8个家庭中7个家庭(87.5%)有2人及2人以上HBV感染或曾经感染,8个家庭共26名家庭成员中14人HBsAg阳性,阳性率为53.8%。共检测了4组母亲和子女的HBV基因,其中3组HBV基因为C型,1组母亲为C型、子女为B型;在肝细胞癌相关HBV变异中,子女的BCP区热点突变频率低于母亲,PreS区C型有8个变异位点在母亲和子女体内均表达、其余关键位点均未在子女体内发现。结论 HBV感染存在明显的家庭聚集性;此次调查结果显示学生HBV感染通过母婴传播可能性较大,但也存在后天血液传播等方式感染;子女HBV基因进化程度低于母亲,符合HBV进化的规律。
关键词:  乙型肝炎病毒  肝细胞癌  家庭聚集性  变异(遗传学)  母婴传播
DOI:10.16781/j.0258-879x.2019.01.0054
投稿时间:2018-04-01修订日期:2018-06-12
基金项目:上海市卫生和计划生育委员会科研课题(201540057),上海市第四轮公共卫生三年行动计划高端海外研修团队项目(GWTD2015S05).
Epidemiological investigation of hepatitis B virus infection and analysis of virus mutations in hepatitis B surface antigen positive students and their frst-degree relatives
XIE Zhen-yu1*,FEI Yi2,YANG Tian2,YIN Jian-hua3,PU Rui3
(1. Department of Prevention and Health Care, Maternity and Child Health Care Hospital of Shanghai Pudong New Area, Shanghai 201206, China;
2. Department of Preventive Immunization, Center of Disease Control and Prevention of Shanghai Pudong New Area, Shanghai 200136, China;
3. Department of Epidemiology, Faculty of Tropical Medicine and Public Health, Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding author)
Abstract:
Objective To explore the infection status of hepatitis B virus (HBV) in families of hepatitis B surface antigen (HbsAg) positive students and the mutations of HBV related to hepatocellular carcinoma, so as to provide theoretic evidence for the prevention and control of HBV infection and hepatocellular carcinoma.Methods A total of 1 611 students were investigated; they were from 60 classes of 15 schools and kindergartens in Pudong New Area, Shanghai, China, and 8 HBsAg positive students were found. These 8 students and their 18 first-degree relatives were enrolled in this study. Venous blood samples were collected to test the 5 markers of hepatitis B using enzyme linked immunosorbent assay. HBV DNA was detected by fluorescent PCR. HBV genome, basic core promoter (BCP) region and PreS region were detected using multiplex-PCR and nested PCR combined with cloning and sequencing.Results The positive rates of HBsAg and HBcAb in the firstdegree relatives were 33.3% (6/18) and 38.9% (7/18), respectively. Both HBsAg and HBcAb positive rates in the mothers were 71.4% (5/7), which were significantly higher than those of the other first-degree relatives (P<0.05). Seven of 8 families (87.5%) had 2 or more members infected or had ever infected with HBV. Fourteen of 26 members in 8 families had positive HBsAg, with a positive rate of 53.8%. A total of 4 groups of mothers and children received gene detection. Three groups of them had type C HBV gene, and 1 group had type C in mother and type B in child. Among the hepatocellular carcinomarelated HBV mutations, the mutation frequency of hot spots in BCP region was lower in the children than that in the mothers. Eight HBV mutation sites of type C in PreS region were found in both the mothers and children, and none of the remaining key sites were found in the children.Conclusion There is obvious family clustering of HBV infection, suggesting that HBV infection of students is more likely to be transmitted through mother-to-child transmission, but there are other ways of infection, such as acquired blood. The evolution degree of HBV gene in children is lower than that in mothers, which conforms to the rule of HBV evolution.
Key words:  hepatitis B virus  hepatocellular carcinoma  family clustering  variation genetics  mother-to-child transmission