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Qu et al. Etiological prevention of liver cancer

prospective study of 22,707 men in Taiwan [17] . In 1992, Beginning in January 1992 universal immunization to
before the national HBV vaccination program was newborns was integrated into the national Expended
implemented, HBsAg seropositive rate in the 1-4 age Program of Immunization (EPI) of China with the family
group was 9.67%, as high as in the general population paying for all the costs [18,19] . Due to the relative high
(9.75%) [15] , reflecting the fact that most of the chronic vaccine cost during that period, the immunization was
infections in Chinese population were acquired in the mainly carried out in some urban areas and the wealthier
perinatal period or in early life. It is instrumental to Eastern provinces of China. From 1 January 2002, the
reduce the incidences and mortalities of HCC and other vaccines were provided for free and the family paid only
liver diseases through universal HBV vaccination for for user fee [18,19] . Between 2002-2007, with the support
infants and children. The Chinese government therefore from the Global Alliance for Vaccines and Immunization
developed a substantial number of policies to promote and the central government of China, HBV vaccination
and implement the vaccination program [18,19] . A brief was fully integrated into routine immunization to all
history of the HBV vaccination program is summarized infants in Western region and in poverty-affected
in Figure 1. counties in the Central regions of China, and from 2008
the central government of China took over the cost [19] .
The plasma-derived HBV vaccine was firstly
manufactured and found to be effective in humans in In 2006 (14 years after universal HBV immunization
clinical trials [20-22] . In 1982 two plasma-derived HBV to newborns), the Chinese government conducted a
vaccines, which were prepared from plasma of chronic national hepatitis serosurvey in the same areas as did
HBsAg carriers, from France and from the United in 1992 by measuring the prevalence of HBV markers
States were licensed [23] . A World Health Organization among the population aged 1-59 years to evaluate the
(WHO) Scientific Group meeting was convened from
Jan 30 to Feb 4, 1983 to discuss HBV vaccination for impact of the HBV vaccination program. Overall, 82,078
the prevention of PLC [24] . Millions of the first-generation persons were surveyed, from whom 82,008 blood
plasma-derived vaccines were administered samples were collected. Among the general population
worldwide to neonates, infants, children, and adults aged 1-59 years, the prevalence of HBsAg, anti-HBs,
at high-risk, and the effectiveness and safety records and anti-HBc were 7.2%, 50.1%, 34.1%, respectively.
are excellent [18,23,25] . Due to the large population and However, the HBsAg prevalence was greatly reduced
high prevalence of HBV in China, the most important among those age < 15 years compared to that found in the
technical issue was to provide a safe and effective 1992 national serosurvey. The HBsAg seroprevalence in
HBV vaccine sufficient to meet the requirement of the 1-4 age group was 0.96% [27] , which was significantly
immunizing 20 million newborns each year as well reduced compared to the same group studied in 1992 [15] .
as other high risk groups. Through technical transfer The HBsAg seroprevalence was also reduced in the
from Merck, China manufactured both plasma-derived 5-59 age group, with a 2.32% seroprevalence in the
and recombinant HB vaccines domestically in late 5-14 age group, and a 5.4% seroprevalence in the 15-19
1980s [18] . With the maturation of recombinant DNA age group, and more than 8.0% in individuals aged 20-
technology, the recombinant vaccines, prepared from 59 years [27] . Further investigation was done in the same
yeasts, or from mammalian cells, were manufactured areas in 2014 among the 1-29 years age group. The
in early 1993, and entirely replaced the plasma-derived HBsAg seroprevalence was 2.64% (95% CI: 2.28-3.06%)
vaccine in 1997 [18,19,26] . in 2014 and decreased by 73.92% as compared with the

1. Plasma-derived HB 1. National hepatitis survey,
vaccine was effective in 68,000 participants aged 1-59
human [20-22] Both plasma-derived and years [15] National hepatitis
2. Two plasma-derived HB recombinant HB vaccines 2. EPI included HB immunization. National hepatitis survey,
vaccines were licensed in were manufactured in Family paid for the cost [18,19] 82,078 participants aged survey, 31,713
participants aged 1-29
France and USA [23] China [18,19] 1-59 years [27] [28]
years
1982 Late of 1980s 1992 2006
2014

1981 1983 1983-84: Pilot. 1985-90: Main 1997 2002-2007 2008
Relationship of HCC A WHO Scientific QHBIS: plasma-derived HB vaccine Recombinant HB GVAI support 50% Free vaccines national
and chronic HBV Group meeting on HB about 80,000 newborns involved vaccine entirely Free vaccines wide. Central
infection [17] vaccination for liver population-based, controlled, replaced plasma- national wide [19] government took over
cancer prevention [24] cluster-randomized [18,33,53] derived HB cost [19]
vaccine [18,19,26]
Figure 1: Brief history of HBV vaccination program in China. HBV: hepatitis B virus; HCC: hepatocellular carcinoma; WHO: World Health
Organization; QHBIS: Qidong Hepatitis B Intervention Study; EPI: Expended Program of Immunization
230 Hepatoma Research ¦ Volume 3 ¦ October 25, 2017