Primary prevention of hepatitis B virus (HBV) infection includes:
- vaccination of non-immune individuals at risk of infection
- prevention of mother-to-child transmission, including routine antenatal testing of all women, universal infant immunisation, and appropriate management and follow-up of both hepatitis B surface antigen (HBsAg)-positive women during pregnancy and their infants (see Chapter 10)
- universal precautions to prevent exposure and post-exposure prophylaxis for individuals exposed to potentially infectious body fluids (see Chapter 12).
Hepatitis B vaccination aims to prevent HBV infection and its complications, which include fulminant hepatitis, cirrhosis, liver failure and hepatocellular carcinoma (HCC). In acute cases, fulminant hepatitis occurs rarely, but it is associated with significant mortality, especially in infants (1).
The World Health Organization (WHO) strategy for the control of HBV infection aims to provide universal infant hepatitis B immunisation, with the first dose given at birth (2). By the end of 2011, global coverage for hepatitis B vaccine in routine childhood vaccination schedules reached 180 countries (93%) (3). The vaccine induces antibodies to hepatitis B surface antigen (anti-HBs), and a titre of 10 mIU/mL or more is considered to be protective against HBV infection. With the introduction of universal infant vaccination programs in countries with a high prevalence of hepatitis B (e.g. Taiwan), universal hepatitis B vaccination programs have had a profound impact on reducing the incidence of chronic infection, dropping the HBsAg prevalence rate in children from 10% to 1% (4), and halving the incidence of HCC in children aged 6–14 years (5, 6).
Target groups for adult vaccination in Australia are essentially the same groups in whom testing for evidence of chronic infection should be considered (see Chapter 3) (7). High-priority groups include:
- household, close and sexual contacts of people with chronic hepatitis B (CHB)
- Aboriginal and Torres Strait Islander people
- people from countries that have a high or intermediate prevalence of hepatitis B.
Other priority groups that should be offered testing and vaccination include men who have sex with men, people living with hepatitis C or human immunodeficiency virus (HIV), people who inject drugs, people in custodial settings and people in at-risk professions. A complete list of the groups that should be considered for vaccination is given in Table 5.1.
Transmission of HBV through blood transfusion and organ transplant has been almost entirely eliminated through the screening of blood and organ donors in Australia. However, there remains a small risk of exposure to HBV for patients with clotting disorders who receive blood-product concentrates.
The modes of transmission still relevant in Australia include:
• household contact
• sexual contact
• re-use of injecting or tattooing equipment
• occupational exposure.
|The Australian National Immunisation program||People at higher risk of hepatitis B virus infection||People prone to exposure or at risk of significant morbidity from exposure||People at risk of occupational exposure|
|As there are state and territory differences, primary care providers should check with their local health departments for information on which of these groups may be entitled to funded vaccination.|
|See The Australian Immunisation Handbook for further information http://www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/Handbook10-home|
In addition to screening blood donors, organ donors and health-care workers for HBV, the strategy to control HBV infection in Australia includes universal hepatitis B vaccination of neonates and the administration of hepatitis B immunoglobulin (HBIG) at birth to neonates born to HBsAg-positive mothers. In the Northern Territory, the hepatitis B vaccine has been routinely administered to Aboriginal and Torres Strait Islander newborns since 1988, and to all newborns since August 1990. The universal infant program began in 2000, with the first dose given at birth. Hepatitis B vaccination for all adolescents commenced in 1997 in some Australian states and territories, but has now been phased out because those immunised for hepatitis B in the infant program have reached adolescence. Non-immune adolescents should still be considered for vaccination, especially those aged 10–13 years who might have fallen through the gap between the introduction of universal infant and the adolescent programs, and susceptible teenage migrants.
|Group||HBsAg prevalence in risk group (%)||Proportion of CHB in Australia (%)|
|People born in high or intermediate-prevalence countries||2.4 (average)
3.6 (Asia and Pacific regions)
2.7 (Africa/Middle East)
|Aboriginal and Torres Strait Islander people||3.7||9|
|People who inject drugs||4||6|
|Men who have sex with men||3||4|
|Non-indigenous Australian-born individuals*||0.3||19|
|Other or not stated||1.0||6|
|*excluding those belonging to the other priority populations listed above CHB, chronic hepatitis B; HBsAg, hepatitis B surface antigen|
The national recommendations for vaccinations are given in the latest edition of the Australian Immunisation Handbook (9). Table 5.3 summarises the vaccines available in Australia.
It is recommended that all newborns receive hepatitis B vaccine within 24 hours of birth, followed by three further doses in infancy, at 2, 4 and 6 months of age. The first dose can be given at 6 weeks of age. If an infant did not receive the birth dose within 7 days of birth, no catch up of that dose is necessary; these infants only require a three-dose course of a hepatitis B-containing combination vaccine, given at 2, 4 and 6 months of age. There should be an interval of at least 8 weeks between doses two and three. The minimum age for administration of dose three is 24 weeks. The type of hepatitis B vaccine used differs between states and territories.
5.4.2 Premature infants
Preterm babies do not respond as well as term babies to hepatitis B vaccine (10). For babies under 32 weeks gestation or less than 2,000 g birth weight, it is recommended to give the vaccine at 0 (within 24 hours of birth), and 2, 4 and 6 months of age and do one of the following:
- measure anti-HBs at 7 months of age and, if antibody titre is less than 10 mIU/mL, give a booster at 12 months of age
- give a booster at 12 months of age without measuring the antibody titre (9).
5.4.3 Infants born to mothers positive for hepatitis B surface antigen with chronic hepatitis B
Infants born to HBsAg-positive mothers should be given HBIG (100 IU), preferably within 12 hours (or at most 48 hours) of birth, in addition to the birth dose of monovalent hepatitis B vaccine (9) (see Chapter 10). The doses should be given at the same time but in separate sites. Monovalent vaccine alone has been shown to be protective and should not be delayed; it is most effective given within 24 hours of birth. In all infants, HBsAg and anti-HBs should be measured at 9–12 months of age (i.e. 3–12 months after completing the course of primary vaccination). If the anti-HBs level is less than 10 mIU/mL, further testing for evidence of HBV infection is advised.
It is recommended that adolescents not vaccinated in childhood receive hepatitis B vaccines (9). Two regimens are available:
- Three-dose regimen for adolescents aged up to 20 years: hepatitis B (paediatric formulation) – three doses of 0.5 mL. The optimal interval is 1 month between the first and second dose, and a third dose 5 months after the second dose.
- Two-dose regimen for adolescents aged 11–15 years: H-B-Vax II 10 μg (adult formulation) or Engerix-B 20 μg (adult formulation) at 0 and 4–6 months.
State and territory health authorities can provide further information on hepatitis B vaccine for this age group (see Appendix 2).
5.4.5 Adults aged 20 years or over
Groups recommended for vaccination (after testing) are listed in Table 5.1.
Monovalent hepatitis B vaccine is usually given in a three-dose schedule, at 0, 1 and 6 month or 0, 2 and 4 month intervals. The minimum interval is 1 month between the first and second doses, 2 months between the second and third doses, and 4 months between the first and third doses. Special consideration is needed for immunocompromised individuals, who may require alternative dosing regimens.
5.4.6 Accelerated vaccination schedules
Two products, Engerix-B (paediatric and adult) and Twinrix (720/20), are registered for use in accelerated schedules, which consist of four doses in total. Accelerated schedules should only be used if there is limited time before departure to endemic regions (Table 5.4).
|Vaccine||Age||Dose (HBsAg protein)||Volume||Schedule|
|Engerix-B (paediatric)||Up to 20 years||10 μg||0.5 mL||0, 1, 2 months; booster at 12 months|
|Engerix-B (adult)*||>20 years||20 μg||1.0 mL||0, 7, 21 days; booster at 12 months or
0, 1, 2 months; booster at 12 months
|Twinrix (720/20)*||>15 years||20 μg||1.0 mL||0, 7, 21 days; booster at 12 months|
|*If time permits, it is recommended that the 0, 1, 2 month schedule be used, because higher seroprotective rates are observed following this schedule than with a 0, 7, 21 day schedule; a booster dose at 12 months is recommended for long-term protection.|
5.4.7 Booster doses
Although vaccine-induced antibody levels decline with time and may eventually become undetectable, booster doses are not recommended in immunocompetent people after a primary course, because there is good evidence that a completed primary course of hepatitis B vaccination provides long-lasting protection. This recommendation includes health-care workers. Booster doses are recommended, however, for people who are immuno-compromised (e.g. those with HIV infection or renal failure).
5.4.8 Hepatitis B testing before vaccination
Testing before vaccination is recommended for those at increased risk of infection (see Chapter 3 and Table 5.2), including people born overseas in high or intermediate-prevalence countries, Aboriginal and Torres Strait Islander people, men who have sex with men, people who inject drugs, sex industry workers, immunocompromised people and people in custodial settings, or those who have been in such settings.
5.4.9 Hepatitis B testing post vaccination
Infants born to HBsAg-positive mothers should be tested 3–12 months after the primary course of vaccination is completed. Testing for post-vaccination response 4 weeks after the primary course is also recommended for:
- health-care workers involved with exposure-prone procedures (see Chapter 12)
- those at risk of severe or complicated disease (e.g. immunosuppressed patients and patients with chronic liver disease)
- those expected to have a poor response to hepatitis B vaccine (e.g. haemodialysis patients)
- those at high risk of acquiring hepatitis B (e.g. contacts of those with CHB, people who inject drugs, sex industry workers, and those living in communities with high prevalence of hepatitis B).
Adverse events that can occur following hepatitis B vaccination include:
- soreness at the injection site (5%), fever (usually low grade, 2–3%), nausea, dizziness, malaise, myalgias and arthralgias. Fever can be expected in some neonates (0.6–3.7%).
- anaphylaxis has been reported in adults, but only rarely
- although various adverse events (e.g. demyelinating diseases, multiple sclerosis, Guillain-Barré syndrome and arthritis) have been reported, there is no evidence of a causal relationship with these events and hepatitis B vaccination (11, 12).
HBIG is prepared from pooled plasma from the blood bank, with samples selected on the basis of high levels of anti-HBs. Its use is recommended in infants born to HBsAg-positive mothers and to non-immune people exposed to blood of people with CHB infection.
HBIG should be given to the newborn within 12 hours of birth, or to adults not previously vaccinated within 72 hours of exposure, because efficacy diminishes with time from 48 hours after exposure.
The hepatitis B vaccine can be given at the same time as HBIG or within 7 days of exposure. Previous vaccination in the exposed adult should be verified by evidence of detectable anti-HBs. If the anti-HBs is undetectable, HBIG dose should be as follows:
- 100 IU children (<30 kg weight)
- 400 IU (>30 kg weight).
A non-responder is a person who has a documented history of an age-appropriate primary course of hepatitis B vaccine, but has never achieved an anti-HBs level of over 10 mIU/mL. In such cases, HBsAg carriage should first be excluded as a cause of failure in vaccine non-responders. For those subjects who have not achieved adequate anti-HBs levels (≥10 mIU/mL) after the third dose of vaccine, a single booster dose (fourth dose) can be given, and anti-HBs checked 4 weeks later. If the anti-HBs level is over 10 mIU/mL the person can be regarded as immune. People who are non-responders after the fourth booster dose should be given two further doses at monthly intervals, followed by testing for response 4 weeks later. A few small studies have reported success with administration of high-dose formulations of double-dose administration for the fourth or subsequent doses. Persistent non-responders should be informed about the need for HBIG within 72 hours of parenteral exposure to HBV. The efficacy of intradermal routes of vaccine administration in non-responders remains unconvincing.
Vaccination failure may occur in people exposed to HBV variants with mutations in the HBV surface gene (vaccine-induced escape mutant). Current hepatitis B vaccines are not effective in preventing infection with these mutants. Most such vaccine-induced escape mutants were initially reported in neonates through vertical transmission and in transplant recipients. These vaccine-induced escape mutants were responsible for most of the 3.4% vaccine failure rate reported in the Chinese adult population undergoing a hepatitis B vaccination program (13).
Hepatitis B vaccination during pregnancy is not routinely recommended. The vaccine can be given to susceptible pregnant women for whom it would otherwise be recommended, including for post-exposure prophylaxis in non-immune women exposed to a HBsAg-positive source (9). Vaccination is not contraindicated in breastfeeding, and breastfeeding in the vaccinated infant to a HBsAg-positive mother poses no additional risk of viral transmission, despite evidence of HBV in breast milk (14).
For further information about these recommendations, please refer to the latest edition of The Australian Immunisation Handbook (9).
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- National HBV Testing Policy Expert Reference Committee. National hepatitis B testing policy. Darlinghurst NSW: Australasian Society for HIV Medicine (ASHM), 2012.
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- Saari TN, American Academy of Pediatrics Committee on Infectious D. Immunization of preterm and low birth weight infants. Pediatrics. 2003;112(1 Pt 1):193–8.
- World Health Organization (WHO). The Global Advisory Committee on Vaccine Safety rejects association between hepatitis B vaccination and multiple sclerosis (MS), 2002.
- Duclos P. Safety of immunisation and adverse events following vaccination against hepatitis B. Expert Opinion on Drug Safety. 2003;2(3):225–31.
- He C, Nomura F, Itoga S, Isobe K, Nakai T. Prevalence of vaccine-induced escape mutants of hepatitis B virus in the adult population in China: a prospective study in 176 restaurant employees. Journal of Gastroenterology and Hepatology. 2001;16(12):1373–7.
- Zheng Y, Lu Y, Ye Q, Xia Y, Zhou Y, Yao Q, et al. Should chronic hepatitis B mothers breastfeed? a meta analysis. BMC Public Health. 2011;11(1):502.