Elimination of Hepatocellular Carcinoma and Acute Hepatitis B in Children 25 Years After a Hepatitis B Newborn and Catch-Up Immunization Program

Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK 99508, USA.
Hepatology (Impact Factor: 11.06). 09/2011; 54(3):801-7. DOI: 10.1002/hep.24442
Source: PubMed


Alaska Native people experience the highest rates of acute and chronic hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) in the United States. We examined the effect of a universal newborn immunization with hepatitis B vaccine and mass population screening immunization program initiated in 1984 on rates of HBV and HCC in children 25 years later. During this time, the population of Alaska Native people grew from an estimated 75,000 to 130,000 persons. A surveillance system to detect acute HBV infection in Alaska Native facilities was established in 1981. Cases of HCC in children under 20 years of age were identified using a National Cancer Institute (NCI)-funded Cancer Registry established in 1969 coupled with an active surveillance program of screening persons with chronic HBV semiannually for alpha-fetoprotein since 1982. The incidence of acute symptomatic HBV infection in persons <20 years of age fell from cases 19/100,000 in 1981-1982 to 0/100,000 in 1993-1994. No cases of acute HBV have occurred in children since 1992. The incidence of HCC in persons <20 years decreased from 3/100,000 in 1984-1988 to zero in 1995-1999 and no cases have occurred since 1999. The number of identified hepatitis B surface antigen-positive children <20 years in the Alaska Native population declined from 657 in 1987 to two in 2008. Conclusion: Universal newborn vaccination coupled with mass screening and immunization of susceptible Alaska Natives has eliminated HCC and acute symptomatic HBV infection among Alaska Native children and this approach is the best way to prevent HBV-related disease in children.

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Available from: Lisa R Bulkow, Feb 25, 2015
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    • "Chronic HBV infection results in serious consequences many years after infection, therefore, directly measuring the impact of the HB vaccination program on reducing morbidity and mortality due to cirrhosis and hepatocellular carcinoma (HCC) in China will not be possible for years and decades. However, the effectiveness of HB vaccination in reducing morbidity and mortality is documented in several countries and populations, and additional prospective cohort studies are underway [11] [12] [13] [14] [15]. We use a published model to estimate the overall impact of HB vaccine for children born in China between 1992, the year routine vaccination was recommended, and 2009, the final year of the CGP. "
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    ABSTRACT: The China GAVI Project (CGP) was initiated in 2002 to provide hepatitis B (HB) vaccine to infants born in the less developed areas of China including the Western provinces and poverty counties of Middle provinces, to prevent the consequences of hepatitis B virus infection. By 2009, the project areas had raised coverage of 3 doses of HB vaccine and timely birth doses to almost 90% among infants, comparable to those in wealthier Eastern provinces, and reduced HBV prevalence to <1% among children in these areas. We estimated the impact in disease prevented by HB vaccine in China between 1992, when the vaccine was routinely recommended, and 2009, and in CGP areas for the years 2003-2009, when the CGP was active. A published model was used to estimate the burden of chronic and acute HBV infection and death prevented due to HB vaccination in China and the CGP areas using data from national serosurveys in China in 1992 and 2006, and HB vaccine coverage from surveys in 2004, 2006 and 2010. We used sigmoid modeling to estimate vaccine coverage nationally, regionally, and CGP areas. We also estimated the incremental impact of the CGP on HB vaccine coverage in those underserved areas. Our findings suggest that between 1992 and 2009, HB vaccination in China has prevented 24million chronic HBV infections and 4.3million future deaths due to cirrhosis, hepatocellular carcinoma and acute hepatitis. During the CGP between 2003 and 2009, an estimated 3.8million chronic HBV infections and 680,000 deaths were prevented in CGP areas. We found that the CGP funding increased HB vaccine coverage in project areas by 4-15% for HB3 and 4-27% for timely birth dose beyond the coverage expected without the CGP. The CGP represents a highly successful public health collaboration between the national government and international partners.
    Vaccine 12/2013; 31S9:J66-J72. DOI:10.1016/j.vaccine.2013.03.043 · 3.62 Impact Factor
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    • "Other long term longitudinal studies of hepatitis B vaccine efficacy have also been conducted in Alaska [25] Taiwan [26], [27] Thailand [28] China [29] and in The Gambia [30]. The latter differs from the current study in that it is a randomised nationwide study but lacks data on peak antibody responses in the later years of follow-up [31]. Similarities between the current study and those previously published have been noted although the level of endemicity and epidemiology of HBV infection has varied with region: vaccine induced antibody decays with time, anti-HBc seroconversion occurs in those with low antibody concentrations, efficacy against chronic infection is maintained and the incidence of acute hepatitis and hepatocellular carcinoma drops dramatically [14], [32]. "
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    ABSTRACT: To determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and asses risk factors for HBV infection and chronic infection. In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1-28 years were tested. A spouse study was conducted in females (aged 14 years and above) and their male partners. Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%), which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1-25.6) of persons with a low peak response (10-99 mIU/ml) had detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high peak response (>999 mIU/ml). Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection. Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.
    PLoS ONE 03/2013; 8(3):e58029. DOI:10.1371/journal.pone.0058029 · 3.23 Impact Factor
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    • "Prevention of perinatal HBV infection from HBV carrier mothers to their infants is critical to eliminate chronic hepatitis B since as high as 90% of the neonatal infections will become chronically infected. Simultaneous administration with one dose (0.5–1 ml, 100–200 IU) of hepatitis B immune globulin (HBIG) within 12 hours after birth and three doses of hepatitis B vaccine on a 0-, 1-, and 6-month schedule, which has been adopted by many countries as well as China as the recommended immunoprophylaxis for infants born to HBV carrier mothers, is highly effective to prevent perinatal HBV infections [3-5]. Up to 2008, 177 countries included the hepatitis B vaccine into their national infant immunization programs [6]. "
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    ABSTRACT: Hepatitis B virus (HBV) infection is endemic in China; perinatal transmission is the main source of chronic HBV infection. Simultaneous administration of hepatitis B immune globulin (HBIG) and hepatitis B vaccine is highly effective to prevent perinatal transmission of HBV; however, the effectiveness also depends on full adherence to the recommended protocols in daily practice. In the present investigation, we aimed to identify gaps in immunoprophylaxis of perinatal transmission of HBV between recommendations and routine practices in Jiangsu Province, China. Totally 626 children from 6 cities and 8 rural areas across Jiangsu Province, China, born from February 2003 to December 2004, were enrolled; 298 were born to mothers with positive hepatitis B surface antigen (HBsAg) and 328 were born to HBsAg-negative mothers. Immunoprophylactic measures against hepatitis B were retrospectively reviewed for about half of the children by checking medical records or vaccination cards and the vaccine status was validated for most of children. Of 298 children born to HBV carrier mothers, 11 (3.7%) were HBsAg positive, while none of 328 children born to non-carrier mothers was HBsAg positive (P < 0.01). The rates of anti-HBs ≥ 10 mIU/ml in children of carrier and non-carrier mothers were 69.5% and 69.2% respectively (P = 0.95). The hepatitis B vaccine coverage in two groups was 100% and 99.4% respectively (P = 0.50), but 15.1% of HBV-exposed infants did not receive the timely birth dose. Prenatal HBsAg screening was performed only in 156 (52.3%) of the carrier mothers. Consequently, only 112 (37.6%) of HBV-exposed infants received HBIG after birth. Furthermore, of the 11 HBV-infected children, only one received both HBIG and hepatitis B vaccine timely, seven missed HBIG, two received delayed vaccination, and one missed HBIG and received delayed vaccination. There are substantial gaps in the prevention of perinatal HBV infection between the recommendations and routine practices in China, which highlights the importance of full adherence to the recommendations to eliminate perinatal HBV infection in the endemic regions.
    BMC Infectious Diseases 09/2012; 12(1):221. DOI:10.1186/1471-2334-12-221 · 2.61 Impact Factor
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