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. 2022 May 17;10(5):793. doi: 10.3390/vaccines10050793

Table 1.

Summary of studies assessing the change of incidence, incidence rates and relative risk (RR) related to hepatitis B vaccination programs.

Author Year Country/
Region		 HCC-Related Outcomes
Chang et al. [16] 1997 Taiwan
  • Average incidence (/100,000) of HCC declined (trend p < 0.01):
    • ○
      1981–1986: 0.7 (range 0.65–0.78)
    • ○
      1986–1990: 0.57 (range 0.48–0.62)
    • ○
      1990–1994: 0.36 (range 0.23–0.48)

  • Incidence rate ratio 1986–1990/1981–1986: 0.63

  • Age-adjusted RR of HCC after July 1990 compared with before: 0.33 (p < 0.001)

  • Age-adjusted risk of death after July 1990 compared with before: 0.51 (p < 0.001)
Lee et al. [17] 2003 Taiwan
  • In age group 0–14 years born in 1996–1999 compared with 1980–1983:
    • ○
      Male mortality decreased by 70%
    • ○
      Female mortality decreased by 62%
Chang et al. [18] 2009 Taiwan Comparing HCC incidence from July 1983 to June 2004:

  • Overall RR 0.31 of HCC development in vaccinated group compared with unvaccinated group

  • Incidence rates of HCC in unvaccinated age groups (/100,000py):
    • ○
      6–9 years: 0.49
    • ○
      10–14 years: 0.56
    • ○
      15–19 years: 0.60
    • ○
      20–24 years: 1.07
    • ○
      25–29 years: 2.28
  • Incidence rates of HCC in vaccinated age groups (/100,000):
    • ○
      6–9 years: 0.15
    • ○
      10–14 years: 0.19
    • ○
      15–19 years: 0.16
  • Rate ratios of HCC development in vaccinated age groups compared with unvaccinated age groups (all p < 0.001)
    • ○
      6–9 years: 0.3 (95% CI 0.18–0.42)
    • ○
      10–14 years: 0.32 (95% CI 0.21–0.49)
    • ○
      15–19 years: 0.30 (95% CI 0.16–0.58)

  • Incomplete vaccination associated with OR 4.32 for HCC development compared with complete vaccination (95% CI 2.34–7.91, p < 0.001)
Chang et al. [19] 2016 Taiwan HCC incidence rates between June 1983 and June 2011 in age group 6–26 years (vaccinated vs. unvaccinated):

  • Overall RR 0.24

  • Overall incidence rate (/100,000 py): 0.92 vs. 0.23

  • Incidence rate ratios for vaccinated/unvaccinated age groups (all p < 0.0001)
    • ○
      6–9 years: 0.26 (95% CI 0.17–0.40)
    • ○
      10–14 years: 0.34 (95% CI 0.25–0.48)
    • ○
      15–19 years: 0.36 (95% CI 0.25–0.51)
    • ○
      20–26 years: 0.42 (95% CI 0.32–0.56)
Hung et al. [20] 2015 Taiwan Annual percentage change in age-standardized incidence rates for age groups from 2003 to 2011 (all p < 0.05):
  • ○

    Children: −16.6% (95% CI −29.7, −1.0,)

  • ○

    Adolescents and young adults: −7.9% (95% CI −10.0, −5.7)

  • ○

    Middle aged: −2.0% (95% CI −2.8, −1.1)

  • ○

    Elderly: 1.3% (95% CI 0.6, 1.9)
Chien et al. [21] 2014 Taiwan
  • Incidence rate of HCC development (per 100,000 y) according to maternal HBsAg/HBeAg status:
    • ○
      HBsAg (−)/HBeAg(−): 0.027
    • ○
      HBsAg (+)/HBeAg(−): 0.162
    • ○
      HBsAg (+)/HBeAg(+): 0.786
  • Incidence rate of HCC development (per 100,000 y) in mothers HBsAg (−)/HBeAg(−)
    • ○
      Vaccination complete: 0.099
    • ○
      Vaccination incomplete: 0.444
  • Incidence rate of HCC development (per 100,000 y) in mothers HBsAg (+)/HBeAg(+)
    • ○
      Ig administered: 0.578
    • ○
      Ig not administered: 1.39
  • Gender-adjusted HR (95% CI) compared with complete vaccination in HBsAg (−)/HBeAg(−) mothers
    • ○
      Vaccination incomplete: 4.4 (1.42–13.65 p = 0.0103)
    • ○
      Ig administered: 5.51 (2.51–12.080 p < 0.0001)
    • ○
      Ig not administered: 12.71 (5.6–28.81) p < 0.0001)
Liao et al. [22] 2021 Taiwan
  • HCC incidence RR in individuals aged <30 across the periods compared with period 1 (pre-vaccination):
    • ○
      Period 2 (post universal vaccination): 1.15 (95% CI 1.00–1.33)
    • ○
      Period 3 (post universal healthcare and screening ultrasounds): 1.4 (95% CI 1.2–1.62)
    • ○
      Period 4 (post national viral hepatitis treatment and surveillance program introduced): 0.9 (95% CI 0.76–1.05)

  • HCC incidence RR in period 2 compared with period 1 in individuals aged 10–29 years: 1.49 (95% CI 1.31–1.7, p < 0.0001)
Wang et al. [23] 2020 Guangxi, China HCC-related mortality in 2017–2018:
  • Age-adjusted mortality rate (/100,000) (Χ2 = 7.9462, p = 0.005)
    • ○
      LongAn: 53.3
    • ○
      BinYang: 45.3
  • Mortality rate (per 100,000) in males ages 20–29 (Χ2 = 0.174, p = 0.667)
    • ○
      LongAn: 2.7 (range 2.5–2.8)
    • ○
      BinYang: 4.7 (range 4.6–4.8)
    • ○
      RR 1.7
  • Mortality rate (per 100,000) in males ages ≥ 30 years (Χ2 = 1.609, p = 0.032)
    • ○
      LongAn: 133.5 (range 132.2–134.8)
    • ○
      BinYang: 116 (range 115.4–117)
    • ○
      RR 0.9
  • Mortality rate (/100,000) in LongAn in age group 20–29 (Χ2 = 5.554, p = 0.018)
    • ○
      2004: 7.9 (range 4.4–11.4)
    • ○
      2017–2018: 1.4 (range 0.4–2.4)
  • Mortality rate (per 100,000) in LongAn in age group ≥ 30 (Χ2 = 0.0412, p = 0.839)
    • ○
      2004: 97 (range 90.6–104.5)
    • ○
      2017–2018: 95.9 (91.3–100.4)
Qu et al. [24] 2014 Qidong, China HCC incidence in children born in 1985–1990 in 41 rural towns across 6 clusters
  • Primary liver cancer incidence rates (per 100,000)
    • ○
      Vaccinated towns: 0.21
    • ○
      Unvaccinated towns: 1.41
    • ○
      HR in vaccinated towns: 0.16 (p = 0.0224)

  • Protective efficacy of vaccination 84%
The Gambia Hepatitis Study Group
[25]		 1987 The Gambia, Africa For the evaluation of protective effect of vaccination on HCC and CLD of children born during the period of 1986–1990 with stepped wedge design of sequential randomization of EPI teams every three months over four-year period, until all EPI teams administering HBV vaccine with other vaccinations.
Long term follow up through the national cancer registry continues.
Outcomes not available at time of publication.
Viviani et al. [26] 2008 The
Gambia, Africa		 65% subjects available for follow up.
With expected cumulative incidence based on age-specific HCC incidence rates from 1987–2002, final outcome for detecting significant impact of vaccination on HCC development will be measurable between 2017 and 2020 when subjects are approximately 30 years old.
Outcomes not available at time of publication.
McMahon, et al. [27] 2011 Alaska, United States of America HCC incidence identified by national cancer institute cancer registry and HCC surveillance program set up by Liver Disease and Hepatitis Program between 1969 and 2008:

  • Incidence of HBV-HCC in 1970s was high with 1/3 HCC cases occurring in <30 years

  • Annual incidence of HCC (/100,000) in children aged < 20 years (p < 0.001 for overall trend)
    • ○
      1984–1988 (peak): 3
    • ○
      1999: 0