title: Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial.
abstract: BACKGROUND
  Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined.
  
  
  RESULTS
  The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR]  = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up.
  
  
  CONCLUSIONS
  Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Qu
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Taoyang
authors.initials: T
authors.lastname: Chen
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Fan
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Lu
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Huang
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Yao
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fan
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China.
authors.forename: Yuanrong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Guoting
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Gao
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Mengya
authors.initials: M
authors.lastname: Zang
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.affiliation: National Office for Cancer Prevention and Control, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Chu Chieh
authors.initials: CC
authors.lastname: Hsia
authors.affiliation: Qidong Liver Cancer Institute, Qidong, Jiangsu Province, China; National Office for Cancer Prevention and Control, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, China; Department of Environmental Health Sciences, Yale School of Public Health, Yale University School of Medicine, New Haven Connecticut, United States of America.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Lab of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zongtang
authors.initials: Z
authors.lastname: Sun
mesh_terms: D002681:China; D006509:Hepatitis B / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D006515:Hepatitis B virus / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D007231:Infant, Newborn; D008107:Liver Diseases / Q000453:epidemiology*; D008113:Liver Neoplasms / Q000453:epidemiology*; D014611:Vaccination / Q000706:statistics & numerical data