A nationwide hepatitis B vaccination program was implemented in Taiwan in July 1984. To assess the effect of the program on the development of hepatocellular carcinoma, we studied the incidence of this cancer in children in Taiwan from 1981 to 1994.
7 October 2009 in JNCI: Journal of the National Cancer Institute
Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma. This population-based study aimed to investigate whether prevention of hepatocellular carcinoma by the universal Taiwanese HBV vaccine program, launched in July 1984, has extended beyond childhood and to identify the predictors of hepatocellular carcinoma for vaccinated birth cohorts. Data on 1958 patients with hepatocellular carcinoma who were aged 6–29 years at diagnosis in Taiwan between 1983 and 2004 were collected from two national hepatocellular carcinoma registries. Age- and sex-specific incidence among vaccinated and unvaccinated birth cohorts were analyzed by using Poisson regression models. All statistical tests were two-sided. Records of 64 hepatocellular carcinoma patients and 5 524 435 HBV vaccinees who were born after the initiation of the vaccination program were compared for HBV immunization characteristics during infancy and prenatal maternal hepatitis B surface antigen (HBsAg) and e antigen (HBeAg) serostatus. Hepatocellular carcinoma incidence was statistically significantly lower among children aged 6–19 years in vaccinated compared with unvaccinated birth cohorts (64 hepatocellular cancers among vaccinees in 37 709 304 person-years vs 444 cancers in unvaccinated subjects in 78 496 406 person-years, showing an age- and sex-adjusted relative risk of 0.31, P < .001, for persons vaccinated at birth). The risk of developing hepatocellular carcinoma for vaccinated cohorts was statistically significantly associated with incomplete HBV vaccination (for those who received fewer than three doses of HBV vaccine, odds ratio [OR] = 4.32, 95% confidence interval [CI] = 2.34 to 7.91); with prenatal maternal HBsAg seropositivity (OR = 29.50, 95% CI = 13.98 to 62.60); with prenatal maternal HBeAg seropositivity (with administration of hepatitis B immunoglobulin at birth, OR = 5.13, 95% CI = 2.24 to 11.71; and without it, OR = 9.43, 95% CI = 3.54 to 25.11). The prevention of hepatocellular carcinoma by this HBV vaccine extends from childhood to early adulthood. Failure to prevent hepatocellular carcinoma results mostly from unsuccessful control of HBV infection by highly infectious mothers.
Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. Before universal HBV immunization was started in Taiwan in 1984, the carrier rate for hepatitis B surface antigen (HBsAg) was 15% to 20% in the general population. To quantify the population impact of a mass vaccination program for HBV 15 years after its implementation. Descriptive analysis of serologic markers of HBV in healthy children and adolescents. Chung-Cheng District, Taipei City, Taiwan, in 1999. 1357 persons younger than 15 years of age, who were born after the implementation of universal HBV vaccination, and 559 persons 15 to 20 years of age, who were born before the program began. Repeated serologic surveys similar to those done before and 5 and 10 years after the national vaccination program was implemented. All participants were tested for serum HBsAg, its antibody (anti-HBs), and hepatitis B core antibody (anti-HBc). During the 15 years since the vaccination program was implemented, the prevalence of HBsAg among persons younger than 15 years of age decreased from 9.8% in 1984 to 0.7% in 1999; among persons 15 to 20 years of age, the 1999 prevalence of HBsAg was 7% (P < 0.001). Hepatitis B core antibody seropositivity, which represents HBV infection, was found in 2.9% of persons younger than 15 years of age and in 20.6% of persons 15 to 20 years of age (P < 0.001); in the same age groups, the rate of anti-HBs seropositivity was 75.8% and 70.7%, respectively (P = 0.02). Universal vaccination significantly decreased the HBV carrier rate and infection rate among children and adolescents born since the program began. By decreasing the carrier pool, continuation of the national HBV immunization program should prevent HBV infection in the children of Taiwan, and, subsequently, adults as well.
Biliary atresia is the most common cause of death from liver disease in children. Although the Kasai operation before 60 days of age can significantly improve prognosis, delay in referral and surgery remains a formidable problem worldwide because of difficulties in differentiating it from benign prolonged neonatal jaundice. We established a universal screening system using an infant stool color card to promote the early diagnosis and treatment of biliary atresia. After a pilot regional study in 2002–2003, a national stool color screening system was established by integrating the infant stool color card into the child health booklet given to every neonate in Taiwan since 2004. Within 24 hours of the discovery of an abnormal stool color, this event is reported to the registry center. The annual incidence of biliary atresia per 10,000 live births in 2004 and 2005 was 1.85 (40/216,419) and 1.70 (35/205,854), respectively. The sensitivity of detecting biliary atresia using stool cards before 60 days of age was 72.5% in 2004, which improved to 97.1% in 2005. The national rate of the Kasai operation before 60 days of age increased from 60% in 2004 to 74.3% in 2005. The jaundice‐free rate (<2 mg/dL) at 3 months after the Kasai operation among infants with biliary atresia in 2004–2005 was 59.5% (44 of 74), significantly higher than the historical data of 37.0% in 1976–2000 before the stool card screening program (P = 0.002). Conclusion: Universal screening using the stool color cards can enhance earlier referral, which may ultimately lead to timely performance of the Kasai operation and better postoperative outcome in infants with biliary atresia. (HEPATOLOGY 2008.)