Infant Hepatitis B Virus Vaccination Research Articles

Hepatitis B Immunization in Health Care Workers: Needs and Opportunities

Hepatitis B Immunization in Health Care Workers: Needs and Opportunities

Natural history of hepatitis B virus infection: pediatric perspective

Hepatitis B virus (HBV) infection is an important disease globally. Chronic HBV infection may result in serious complications. Its transmission may be either perinatal or horizontal. Perinatal transmission is particularly important after the implementation of a universal vaccination program. Through either route, chronic carrier status is usually established in early childhood. The course of the disease course is determined by the host-virus interaction. The host's immune system initially tolerates the virus, and then gradually attempts to clear it. The virus, on the other hand, tries to avoid host immune system attack by a strategy involving targeted epitope mutations. By generating mutants, the virus can survive attacks from the host's immune system, enabling the infection to persist. Different individuals have different responses to HBV infection; genetic polymorphisms in cytokines, hormones, and other immune modulators may affect the final outcome of chronic HBV infection. Due to the implementation of a universal infant HBV vaccination program, HBV infection is now under control. Unfortunately, there still are some cases of vaccination failure. Very high maternal viremia, in utero infection, or escape mutants are possible reasons for vaccination failure. Immunocompromised hosts also risk vaccination failure. Blood or organ donors with occult HBV infection are possible sources for immunocompromised hosts. These victims of vaccination failure may exhibit a different disease course due to chronic HBV infection from those who acquired the infection before the universal vaccination era. The achievement of our ultimate goal of HBV elimination depends on a globally effective universal vaccination program, as well as the application of some novel successful medications to control those who are already infected.

Hepatitis B vaccination in children: The Taiwan experience

The world's first nationwide hepatitis B virus (HBV) universal vaccination program for infants was launched in Taiwan in July, 1984. All infants received three to four doses plasma or recombinant HBV vaccines. In addition, infants of HBeAg-positive mothers received 0.5 ml of hepatitis B immunoglobulin within 24 hours after birth. The vaccination coverage rate is as high as 97%. Seroprevalence of hepatitis B surface antigen (HBsAg) declined from 9.8% (prevaccination period) to 0.6% in children in Taipei City after 20 years of mass vaccination. The seropositive rates for HBsAg, antibody to HBsAg, and antibody to hepatitis B core antigen were 1.2%, 50.5%, and 3.7%, respectively, in those born after the vaccination program (< 20 years old) in 2004. In line with the decrease of chronic HBV infection, the incidence of hepatocellular carcinoma (HCC) also decreased in children in Taiwan. From 1981 to 1994, the incidence of HCC in 6- to 9-year-olds declined from 0.52/100,000 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 ( p < 0.001). We extended the observation to 2000, the incidence of HCC per 100,000 children declined from 0.54 to 0.20. The prevalence of a determinant mutants (amino acids 121–149 of HBsAg) in Taiwanese carrier children was 7.8% (eight out of 103) in 1984, increased to 19.6% (10 out of 51) in 1989, peaked at 28.1% (nince out of 32) in 1994, and remained stationary at 23.1% (three out of 13) and about 25% in 1999 and 2004, respectively; it was higher in those fully vaccinated compared with those not vaccinated. The other group of subjects who are susceptible to vaccine failure is the immunocompromized hosts. We observed some de novo HBV infection in children after liver transplantation. Despite of the success of hepatitis B immunization, childhood chronic HBV infection and HCC were not eliminated by the universal vaccination program. Among those HBsAg carriers born after the vaccination program, 89% of their mothers were found to be positive for HBsAg, indicating the importance of maternal transmission. This was also true in the mothers of children with HCC, of them 96% were HBsAg positive. After two decades of universal infant HBV vaccination, we found this program provides long-term protection for up to more than 20 years, and a universal booster is not required for the primary HBV vaccinees before adulthood. Mother-to-child transmission, although largely diminished, is still the main cause for immunoprophylaxis failure. The emergence of escape mutant did not impose increased risk of chronic infection at present. Nevertheless, development of new vaccines may overcome the vaccine failure.

Clinical course ofde novohepatitis B infection after pediatric liver transplantation

The characteristics of hepatitis B virus (HBV) in vaccinated children who acquire de novo HBV infections after orthotopic liver transplantation (OLT) remain largely unknown. The aim of this study was to explore HBV mutants in pediatric OLT recipients with de novo HBV infections. In all, 50 recipients underwent OLT between December 1997 and October 2005, and they were regularly checked for HBV serum markers from November 2005 to April 2009. Before OLT, all were hepatitis B surface antigen (HBsAg)-negative and under the coverage of the universal infant HBV vaccination program. Those who became HBsAg-positive after OLT were diagnosed with de novo HBV infection. HBV viral loads and full-length genome sequencing were determined when the diagnosis of de novo HBV infection was established. Nine patients (9/50, 18%) acquired de novo HBV infections after OLT. None had graft loss or fulminant hepatitis. Five cleared HBsAg, and 4 of the 5 even recovered with antibody to hepatitis B surface antigen (anti-HBs) formation. The other 4 were persistently HBsAg-positive. Mutations in the major S gene (681 base pairs) were discovered in 8 (88.9%) of the de novo HBV-infected children. Six of them harbored mutations within the "a" determinant region (codons 124-147), whereas the other 2 had mutations outside this region. These 2 cleared HBsAg and recovered with anti-HBs formation. HBV DNA levels were not different between those who cleared HBsAg and those who did not. In conclusion, surface mutants are frequent among pediatric liver transplant recipients with de novo HBV infections, but their clinical relevance requires further study.

Hepatitis B‐related hepatocellular carcinoma: epidemiological characteristics and disease burden

Worldwide, 350 million people are chronically infected with hepatitis B virus (HBV) who are at greater risk of hepatocellular carcinoma (HCC) compared with uninfected people. The relative risks of HCC among people infected with HBV ranges from 5 to 49 in case-control studies and from 7 to 98 in cohort studies. More than 50% of HCC cases worldwide and 70-80% of HCC cases in highly HBV endemic regions are attributable to HBV. Incidence of HCC (per 100,000 person/year) among people with chronic HBV infection ranges from 400 to 800 in male and from 120 to 180 in female. Factors associated with increased risk of HCC include demographic characteristics (male sex and older age), lifestyles (heavy alcohol consumption and smoking), viral factors (genotype C, D F, high level of HBV DNA, core/precore mutation) and clinical factors (cirrhosis, elevated alpha-fetoprotein (AFP) and alanine aminotransferase (ALT)). HBV-related HCC has extremely poor prognosis with median survival less than 16 months. Survival rates of HBV-related HCC ranged from 36% to 67% after 1 year and from 15% to 26% after 5 year of diagnosis. Older age, liver function impairment, vascular invasion, tumour aggressiveness and elevated AFP are associated with HCC survival. Global burden of HBV-related liver disease is still a major challenge for public health in the 21st century. While decreases in incidence of HBV infection have been observed in birth cohorts following the introduction of universal infant HBV vaccination programme, HBV-related HCC incidence in is projected to increase for at least two decades because of the high prevalence of chronic HBV infection and prolonged latency to HCC development. To reduce HBV-related HCC continued expansion of universal infant HBV vaccination is required along with antiviral therapy targeted to those individuals at highest risk of HCC. Broad public health strategies should include routine testing to identify chronic HBV infection, improved health infrastructures including human resource to provide diagnosis and treatment assessment.

Benefits of Early Hepatitis B Immunization Programs for Newborns and Infants

Despite the availability of safe and effective hepatitis B virus (HBV) vaccines for >20 years, strategies targeting risk groups failed to sufficiently control hepatitis B disease at the population level; this is mainly because of difficulties in risk identification and in program implementation. Hence, the global burden of disease of HBV still is substantial. The World Health Organization recommends universal vaccination against hepatitis B to ultimately eliminate HBV; this recommendation had been progressively implemented to reach 168 countries with a universal program by the end of 2006. However, hepatitis B immunization is currently becoming endangered of losing its place on the agendas of governments, agencies, and international organizations, mainly because of the increasing success of these immunization programs and the interest in newer vaccine-preventable diseases and the related programs.This publication aims to show that vaccination programs targeting newborns and infants are preferable to achieve this goal. The benefits of universal HBV vaccination for newborns and infants are: higher impact on chronic carrier rate and transmission; established potential of high vaccine coverage in this age group; opportunities to combine HBV vaccination with existing universal vaccination programs for newborns and infants; and impact on perinatal transmission, if vaccination is started shortly after birth. Moreover, the safety, immunogenicity, and long-term efficacy of newborn and infant HBV vaccination have been proven extensively. In summary, newborn and infant HBV vaccination programs should be considered the preferred strategy, capable of providing important and sustained impact on global HBV incidence, even if they have a delayed impact on sexual transmission of HBV.

Inadequate Humoral Immunogenicity to Recombinant Hepatitis B Virus Vaccine in Biliary Atresia Children

This study aimed to investigate the primary immunogenicity and the long-term efficacy of recombinant hepatitis B virus (HBV) vaccine in biliary atresia (BA) children. Fifty BA infants (age, 11 +/- 3.9 mo), and 23 BA patients at childhood (age, 8.5 +/- 0.22 y) were included for the evaluation of HBV surface antibody (anti-HBs) levels after three doses of recombinant HBV vaccine immunization. Age- and gender-matched healthy infants (n = 50) and children (n = 23) were enrolled as the control group. Serum samples of the study populations were collected for HBV seromarkers determination. In the absence of hepatitis B virus core antibody and HBV surface antigen, serum anti-HBs level above 10 IU/L was considered adequate immunogenicity to HBV vaccine. The prevalence of adequate anti-HBs levels after recombinant HBV vaccine in BA infants was significantly lower than those of the controls (p = 0.006). There was no difference in the prevalence between childhood BA patients and their matched controls (p = 0.538). In conclusion, adequate primary humoral immunity after the standard doses of recombinant HBV vaccine in BA infants is hard to establish. However, once immunity is acquired, BA children have adequate anti-HBs titer in the long run.

Time for Renewed Commitment to Viral Hepatitis Prevention

Over the last 2 decades, successful public health interventions have altered the epidemiology of viral hepatitis in the United States. Vaccination of children and adolescents has reduced the incidence of hepatitis A virus (HAV) and hepatitis B virus (HBV) infections to historic lows. American Indians/Alaskan Natives, a population whose HBV rate was once 5 times that of other racial/ethnic populations, now has the lowest (0.5 cases per 100 000).1–3 Since the adoption in 1991 of a strategy to eliminate HBV transmission, HBV vaccination of infants, children, and adolescents has largely contributed to an 81% decline in new cases of HBV, and infant HBV vaccination is now on par with that of other vaccines in the childhood schedule. (1,2,4,5) With more than 90% of pregnant women screened for HBV infection and postexposure prophylaxis 85% to 95% effective in preventing mother-to-child HBV transmission at delivery, substantial progress has been made in the prevention of perinatal HBV infections.4 In the absence of a vaccine to prevent HCV, the advent of laboratory testing in 1992 to protect the nation’s blood supply and prevention efforts to reduce risk behaviors among injection drug users (IDUs) have led to a 78% decline in new HCV infections.1,2,6 Health care–related transmission of HBV and HCV is now rare thanks to widespread vaccination of health care workers and the adoption of universal infection control procedures.7 Although these prevention successes are remarkable, challenges remain. Despite the existence of risk-based vaccination recommendations, HAV and HBV infections remain common.3,5 In 2006, an estimated 32000 persons were infected with HAV, with risks highest among international travelers, individuals in close contact with infected persons, men who have sex with men, and IDUs; food-borne outbreaks also continue to be reported.2 Of an estimated 46000 new HBV infections in 2006, more than 80% were attributable to injection drug use and high-risk sexual activity.2,5 Children continue to be infected at birth. Of approximately 24000 infants born to HBV-infected women annually, only about one quarter complete case management and are tested for infection or susceptibility (CDC, unpublished data, 2007). In 2006, a total of 86 perinatal HBV cases were reported to the CDC, but testing and reporting are incomplete; thus, the true number of perinatal HBV cases per year is likely 10 to 20 times higher. Approximately half of persons with chronic HBV in the United States are Asian Americans (CDC, unpublished data, 2006). HBV-related liver cancer is a leading cause of cancer deaths in this population.8 Although the incidence of HBV infection in the United States is declining, the prevalence of chronic HBV is sustained by immigration from HBV-endemic countries in Asia, Africa, and Eastern Europe; each year, an estimated 40000 persons with chronic HBV immigrate to the United States from these countries.5 In 2006, approximately 20000 persons were infected with HCV.2 Injection drug use was responsible for most of these new cases, and at least one third of IDUs are HCV infected.9 Despite the decline in the number of new infections, the number of persons with chronic viral hepatitis is over 4 million, including 3.2 million chronic HCV infections and 800 000 to 1.4 million chronic HBV infections (CDC, unpublished data, 2006).10 Chronic viral hepatitis is a major cause of morbidity responsible for approximately two thirds of chronic liver disease and conservatively 9000 deaths per year. 11,12 Mortality from HCV is expected to rise as the HCV-infected population ages, extending their years of living with the infection and increasing their risk of liver cirrhosis and cancer.13 Cofactors such as HIV infection and alcohol use accelerate the progression of HCV; approximately 25% of the 1 million persons infected with HIV are co-infected with HCV.6 Finally, cases of health care–associated HBV and HCV transmission continue to occur. The changing epidemiology of viral hepatitis reveals both gaps in the delivery of proven interventions and new opportunities to reduce the health consequences of chronic disease. The Centers for Disease Control and Prevention (CDC) has identified new priorities to improve current programs and develop new prevention goals.

An enormous hepatitis B virus‐related liver disease burden projected in Vietnam by 2025

Hepatitis B virus (HBV) is the major cause of chronic liver disease in Vietnam. This study aimed to estimate and project chronic HBV prevalence and HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) for the period 1990-2025. The Vietnamese population for the period 1990-1999 was derived from census data to 1999 and from 2000 to 2025 based on projection data from the United States Census Bureau. Population chronic HBV prevalence for males and females was estimated based on age-specific HBV prevalence from Vietnamese community-based studies. Universal infant HBV vaccination from 2003 was assumed to reduce HBV infection by 90% in subsequent birth cohorts. Incidences of HBV-related LC and HCC by HBV DNA levels from the Taiwanese REVEAL studies were applied to the chronic HBV population to estimate and project HBV-related liver disease burden. Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV-related LC and HCC incidence increased linearly from 21,900 and 9400 in 1990 to 58,650 and 25,000 in 2025. Estimated HBV-related mortality increased from 12,600 in 1990 to 40,000 in 2025. Over the next two decades, universal infant HBV vaccination will reduce chronic HBV prevalence in Vietnam but HBV-related liver disease burden will continue to rise. A national HBV strategy is required to address this expanding burden of liver disease.

Long-term protection against HBV chronic carriage of Gambian adolescents vaccinated in infancy and immune response in HBV booster trial in adolescence.

BackgroundChronic infection with hepatitis B virus (HBV) arising in childhood is associated with hepatocellular carcinoma in adult life. Between 1986 and 1990, approximately 120,000 Gambian newborns were enrolled in a randomised controlled trial to assess the effectiveness of infant HBV vaccination on the prevention of hepatocellular carcinoma in adulthood. These children are now in adolescence and approaching adulthood, when the onset of sexual activity may challenge their hepatitis B immunity. Thus a booster dose in adolescence could be important to maintain long-term protection.MethodsFifteen years after the start of the HBV infant vaccination study, 492 vaccinated and 424 unvaccinated children were identified to determine vaccine efficacy against infection and carriage in adolescence. At the same time, 297 of the 492 infant-vaccinated subjects were randomly offered a booster dose of HBV vaccine. Anti-HBs was measured before the booster, and two weeks and 1 year afterwards (ISRCTN71271385).ResultsVaccine efficacy 15 years after vaccination was 67.0% against infection as manifest by anti-HBc positivity (95% CI 58.2–74.6%), and 96.6% against HBsAg carriage (95% CI 91.5–100%). 31.2% of participants had detectable anti-HBs with a GMC of 32 IU/l. For 168 boosted participants GMC anti-HBs responses were 38 IU/l prior to vaccination, 524 IU/l two weeks after boosting, and 101 IU/l after 1 year.ConclusionsHBV vaccination in infants confers very good protection against carriage up to 15 years of age, although a large proportion of vaccinated subjects did not have detectable anti-HBs at this age. The response to boosting persisted for at least a year.Trial RegistrationControlled-Trials.com ISRCTN71271385