Long-term Effects of Hepatitis B Immunization of Infants in Preventing Liver Cancer.
The incidence of hepatocellular carcinoma (HCC) increases with age, but protective antibody responses decrease with time after infants are immunized against hepatitis B virus (HBV). We investigated whether immunization of infants against HBV prevents their developing HCC as adults. We also searched for strategies to maximize the cancer-preventive effects.



We collected data from 2 Taiwan HCC registry systems on 1509 patients (6-26 years old) diagnosed with HCC from 1983 through 2011. Data on history of HBV immunization and prenatal maternal levels of HBV antigens of all HCC patients born after July 1984 were retrieved from the HBV immunization data bank of the Taiwan Center for Disease Control. We collected data on birth cohort-specific populations (6-26 years old) of Taiwan using the National Household Registry System. Rates of HCC incidence per 10(5) person-years were derived by dividing the number of patients with HCC by the person-years of the general population. Relative risks (RR) for HCC were estimated by Poisson regression analysis in vaccinated vs unvaccinated birth cohorts. We stratified patients by age group to evaluate the association of birth cohorts and HCC risks.



Of the 1509 patients with HCC, 1343 were born before, and 166 were born after, the HBV vaccination program began. HCC incidence per 10(5) person-years was 0.92 in the unvaccinated cohort and 0.23 in the vaccinated birth cohorts. The RRs for HCC in patients 6-9 years old, 10-14 years old, 15-19 years old, and 20-26 years old who were vaccinated vs unvaccinated were 0.26 (95% confidence interval [CI], 0.17-0.40), 0.34 (95% CI, 0.25-0.48), 0.37 (95% CI, 0.25-0.51), and 0.42 (95% CI, 0.32-0.56), respectively. The RR for HCC in 6- to 26-year-olds was lower in the later vs the earlier cohorts (born in 1992-2005 vs 1986-1992; P < .001 and 1986-1992 vs 1984-1986; P < .002). Transmission of HBV from highly infectious mothers and incomplete immunization were associated with development of HCC.



Based on an analysis of 1509 patients with HCC in Taiwan, immunization of infants against HBV reduces their risk of developing HCC as children and young adults. Improving HBV vaccination strategies and overcoming risk factors could reduce the incidence of liver cancer.
Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: changmh@ntu.edu.tw.
Mei-Hwei
MH
Chang
Department of Public Health, College of Medicine, Bigdata Research Center, Fu-Jen Catholic University, New Taipei, Taiwan.
San-Lin
SL
You
Academia Sinica, Taipei, Taiwan.
Chien-Jen
CJ
Chen
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
Chun-Jen
CJ
Liu
Division of Hepatogastroenterology, Department of Pediatrics, Chang Gung University and Hospital, Linkou, Taiwan.
Ming-Wei
MW
Lai
Department of Pediatrics, Taipei Veterans General Hospital, and School of Medicine, National Yang Ming University, Taipei, Taiwan.
Tzee-Chung
TC
Wu
Department of Pediatrics, Division of Gastroenterology, China Medical University Hospital, Taichung, Taiwan.
Shu-Fen
SF
Wu
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Chuan-Mo
CM
Lee
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Faculty of Medicine, National Yang-Ming University, Taichung, Taiwan.
Sheng-Shun
SS
Yang
Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
Heng-Cheng
HC
Chu
Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Tsang-Eng
TE
Wang
Department of Pediatrics, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.
Bor-Wen
BW
Chen
Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Wan-Long
WL
Chuang
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Chang-Hua, Taiwan.
Maw-Soan
MS
Soon
Division of Gastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.
Ching-Yih
CY
Lin
Institute of Public Health, National Yang-Ming University, and Ministry of Health and Welfare, Health Promotion Administration, Taipei, Taiwan.
Shu-Ti
ST
Chiou
Ministry of Health and Welfare, Centers for Disease Control, Taipei, Taiwan.
Hsu-Sung
HS
Kuo
Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Academia Sinica, Taipei, Taiwan.
Ding-Shinn
DS
Chen
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D002648:Child; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control; D017325:Hepatitis B Vaccines / Q000008:administration & dosage*; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D012042:Registries; D012044:Regression Analysis; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D013995:Time; D014611:Vaccination / Q000379:methods / Q000706:statistics & numerical data*; D055815:Young Adult
D017325:Hepatitis B Vaccines
Cancer Prevention; Liver Carcinogenesis; Population Study; Viral Hepatitis