摘要
目的 探讨肝癌高发区新生儿乙型肝炎疫苗接种对肝癌的预防效果。方法 于1983—1990年设立启东乙型肝炎干预队列，创建队列时采用整群抽样法，以农村公社为基础单位，用单纯随机法决定母亲户口所在公社的新生儿乙型肝炎疫苗接种情况，设立了新生儿乙型肝炎疫苗接种组和对照组。新生儿乙型肝炎疫苗接种组共计纳入41 182名儿童，其中40 211名（97.64%）在出生后0、1、6个月完成了3剂5 μg血源性乙型肝炎疫苗接种，28 988名在10~14岁接受了1剂10 μg重组乙型肝炎疫苗加强。对照组共41 730名，在新生儿期无干预，其中23 368名在10~14岁补种了3剂10 μg重组乙型肝炎疫苗。1996—2000年以及2008—2012年分别在研究对象10~11和19~28岁时进行了血清学随访，采集血样、测定了乙型肝炎病毒（HBV）感染标志物。通过中国肿瘤登记系统及全死因登记数据获得肝癌发病、HBV相关肝脏疾病死亡数据，随访至2016年12月31日。采用Cox比例风险模型分析不同时期乙型肝炎疫苗接种对原发性肝癌（PLC）与其他肝病的HR值，并计算疫苗保护率。结果 1996—2000年新生儿乙型肝炎疫苗接种组对象HBsAg阳性率为2.16%（491/22 689），低于对照组的9.08%（1 126/12 395）（χ2=896.61，P〈0.001）。2008—2012年新生儿乙型肝炎疫苗接种组的HBsAg阳性率为1.83%（319/17 386），低于对照组的6.77%（1 222/18 060）（χ2=518.05，P〈0.001）。1996—2000年新生儿期乙型肝炎疫苗接种对10~11岁人群HBsAg阳性的保护效率为79% （95%CI：76%~81%）。2008—2012年乙型肝炎疫苗对19~28岁对象慢性HBV感染的保护率为74% （95%CI：71%~78%）。对照组于10~14岁补种3剂10 μg重组乙型肝炎疫苗，至成年期，HBsAg携带的保护率仅为21% （95%CI：11%~30%）。截至2016年12月31日，疫苗组和对照组PLC发病例数分别为4和17例，新生儿期乙型肝炎疫苗接种对33岁以下人群PLC保护率为79% （95%CI：36%~93%）。结论 在新生儿期实施乙型肝炎疫苗接种是预防慢性HBV感染和肝癌的关键。
Objective Incidence of primary liver cancer （PLC） in China is mostly related to chronic infection of hepatitis B virus （HBV）. Qidong was one of the endemic areas with high incidence of PLC in China before 2000. We conducted a series of studies regarding on PLC etiological prevention during the past decades to develop better primary prevention strategies for PLC.Methods Qidong Hepatitis B Intervention Study was conducted in 1983-1990. A total of 41 182 newborns were randomly assigned to vaccination group and 40 211 （97.64%） of them completed the three-dose, 5 μg-plasma-derived hepatitis B （HB） vaccination series at age 0, 1, 6 month. Among them, 28 988 participants received one-dose 10 μg recombinant HB booster vaccination at age 10-14 years. A total of 41 730 newborns were randomly assigned to the control group. When they were at age 10-14 years, 23 368 participants received the catch-up vaccination with three-dose, 10 μg-recombinant HB vaccine. Two cross-sectional HBV serology surveys were conducted in 1996-2000 and 2008-2012. Information on PLC incidence and mortality of chronic liver diseases were collected through cancer registry and vital statistics until December 31, 2016. Cox proportional hazard models were employed to compute hazard ratio （HR） of PLC and other liver diseases for the participants with neonatal HB vaccination or catch-up vaccination, and the protective efficacy was also calculated.Results During serologic survey in 1996-2000, a total of 22 689 participants in vaccination group and 12 395 participants in control group donated blood samples. The HBsAg seropositive rates in the vaccination group was 2.16% （491/22 689）, which is significantly lower than that of control group （9.08%, 1 126/12 395） （χ2=896.61, P〈0.001）. During serologic survey in 2008-2012, a total of 17 386 participants in vaccination group and 18 060 participants in control group donated blood samples. The HBsAg seropositive rates in the vaccination group was 1.83% （319/17 386）, which is still significantly lower than that of control group （6.77%,1 222/18 060） （χ2=518.05, P〈0.001）. By December 31, 2016, 4 cases of PLC in the vaccination group and 17 cases of PLC were identified in the vaccination and control group, respectively. The estimated efficacy of neonatal HB vaccination on HBsAg seroprevalence in childhood （at age 10-11 years）, early adulthood （at age 19-28 years） and incidence rate of PLC at age below 33 years was 79% （95%CI： 76%-81%）, 74% （95%CI： 71%-78%） and 79% （95%CI： 36%-93%）, respectively. The estimated efficacy of three-dose, 10 μg-recombinant HB catch-up vaccination in early adulthood is 21% （95%CI： 11%-30%）, which is significantly lower than that of neonatal HB vaccination.Conclusion HB vaccination to neonates/infants is crucial against chronic HBV infection in childhood through young adulthood, and subsequently reduced the risk of PLC in young adults.
作者
王宇婷
陈陶阳
朱健
焦宇辰
曲春枫
Wang Yuting, Chen Taoyang, Zhu Jian, Jiao Yuchen, Qu Chunfeng(National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, Chin)
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2018年第4期402-408,共7页
Chinese Journal of Preventive Medicine
基金
国家科技重大专项（2012ZX10002008、2017ZX10201201-006-003）
国家重点基础研究发展计划（2013CB910303）
国家自然科学基金（81571620）
