Contents

8 Hepatitis B

8.5 Recommended immunisation schedule

8.5.1 Recommendations

Individuals recommended to have a primary course of hepatitis B vaccine are described in Table 8.1.

Table 8.1: Hepatitis B vaccine recommendations, funded and unfunded

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for the number of funded doses and any changes to the funding decisions.

Recommended and funded
Household or sexual contacts of HBsAg-positive patients (ie, patients with acute or chronic HBV infection)
Babies of HBsAg-positive mothers (ie, mothers with acute or chronic HBV infection) – require a birth dose plus the primary series (HBIG is also given to these babies at birth)
Children aged under 18 years, including those who have not achieved positive serology and who require additional vaccination 
HIV-positive patientsa
Hepatitis C-positive patients (who should also receive hepatitis A vaccine, although this is not currently funded)
Following non-consensual sexual intercourse 
Following immunosuppressiona,b
Transplant patientsa,c
Dialysis patientsa,c
Following needle-stick injury
Recommended, not funded
Adults at occupational risk (see section 4.6)
Adults at risk of infection by sexual exposure:
  • people seeking evaluation or treatment for a sexually transmitted infection
  • people with a high number of sexual partners
  • people who have sex with commercial sex workers
  • men who have sex with men
Individuals with haemophilia and other regular recipients of blood products
Prison inmates
Current or recent injecting drug users
Migrants from HBV endemic countriesd
Individuals with developmental disabilities
Travellers to HBV endemic regionsd
a See also section 4.3.
b The period of immunosuppression due to steroid or other immunosuppressive therapy must be longer than 28 days.
c The 40 µg dose of hepatitis B vaccine is recommended for adult dialysis patients or for adult liver or kidney transplant patients. See Table 8.2.
d See the CDC website for countries with high hepatitis B prevalence (http://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/hepatitis-b). Consider combined Hep A and B vaccination for travellers to these regions.

8.5.2 Immunisation scheduleTop

The hepatitis B vaccine doses and immunisation schedules vary according to the age of the individual. These are summarised in Table 8.2 below.

Newborn babies

For babies born to HBsAg-positive mothers, a birth dose of 5 µg of Hep B vaccine plus hepatitis B immunoglobulin are recommended, plus the usual childhood Schedule at ages 6 weeks, 3 and 5 months. See section 8.5.3 for more detailed information, including serological testing at age 9 months.

Infants

A primary course of hepatitis B vaccination is given as three doses of DTaP-IPV-HepB/Hib at ages 6 weeks, 3 months and 5 months. If a course of immunisation is interrupted for any reason, it may be resumed without repeating prior doses (see Appendix 2).

Adolescents

Hepatitis B vaccine is recommended and funded for everyone aged under 18 years. If the hepatitis B vaccine is not given during the first year of life, three doses of vaccine are recommended (follow the manufacturer’s recommendations). A two-dose accelerated regimen for adolescents aged 11–15 years, with the second dose four to six months after the first, is useful to improve compliance in this age group. See also Appendix 2 for catch-up schedules.

Adults

For adults, the vaccine manufacturers recommend three doses of 10 µg hepatitis B vaccine spaced at zero, one and six months. (Note that three 40 µg doses are recommended for certain high-risk adults; see section 8.5.3). Shorter intervals between the second and third doses lead to lower antibody levels but equivalent seroconversion and therefore adequate protection.

In healthy adults, a two-dose schedule separated by six months,27 a three-dose schedule given over three weeks,28 and various other accelerated schedules have led to seroconversion rates equivalent to those obtained when following the usual recommended schedule. In general, three doses separated by four-week intervals are recommended, but the doses may be delivered at weekly intervals if more rapid protection is needed.

Table 8.2: Summary of funded hepatitis B vaccine doses and immunisation schedules

Note: Funded conditions are in the shaded rows. See the Pharmaceutical Schedule (www.pharmac.govt.nz) for the number of funded doses and any changes to the funding decisions.

Who Vaccine Dose Volume (mL) Number of doses Schedule
Babies born to HBsAg-positive mothers Hep B
(HBvaxPRO)
5 µg 0.5 1 As close to birth as possible, then continue with usual childhood schedule, plus serological testing at 9 months of age
Babies born to HBsAg-negative mothers (usual schedule) DTaP-IPV-HepB/Hib
(Infanrix-hexa)
10 µg
(hepatitis B component)
0.5 3 6 weeks, 3 months, 5 months
Catch-up for unvaccinated children/ adolescents aged 6 weeks to under 18 years DTaP-IPV-HepB/Hib
(Infanrix-hexa)

OR
10 µg
(hepatitis B component)
0.5 3 0, 1 and 6 months
 
Hep B
(HBvaxPRO)
5 µg 0.5 3 0, 1 and 6 months
Accelerated schedule for adolescents
11–15 years
Hep B
(HBvaxPRO)
10 µg 1.0 2 0, 4–6 months
Eligible adults ≥18 years:          
  • Dialysis patients, liver or kidney transplant patients
Hep B
(HBvaxPRO)
40 µg 1.0 3 0, 1 and 6 months*
  • All other eligible adults
Hep B (HBvaxPRO) 10 µg 1.0 3 0, 1 and 6 months*
* Check the manufacturer’s data sheet for accelerated immunisation schedules.

8.5.3 Special casesTop

Babies of HBsAg mothers

The routine schedule for these infants is a birth dose plus HBIG, then three doses of hepatitis B (as DTaP-IPV-HepB/Hib) at ages 6 weeks, 3 months and 5 months. All pregnant women should receive antenatal screening for hepatitis B infection by testing for HBsAg (see section 8.5.5). Babies of HBsAg-positive mothers are to be notified at birth using the form HE1446: Consent for hepatitis B vaccine and hepatitis B immunoglobulin and notification to the Medical Officer of Health, available from www.healthed.govt.nz or the local authorised health education resource provider or public health unit.

Babies born to HBsAg-positive mothers should receive:
  • 100–110 IU hepatitis B immunoglobulin (HBIG) neonatal, at or as close as possible to birth
  • ​a birth dose of hepatitis B vaccine (HBvaxPRO, 5 µg), which should be given at or as close as possible to birth (preferably within 12 hours).
If HBIG and/or hepatitis B vaccine is inadvertently omitted, administer as soon as the omission is recognised. HBIG can be administered up to seven days post-delivery. If there is a delay for longer than seven days, seek specialist advice.

These babies should then continue as per the Schedule at ages 6 weeks, 3 months and 5 months. Serological testing is required at 9 months of age (see below).

The vitamin K injection may also be given at the same time, in the same limb as the HBIG, but not at the same site.

Occasionally women have not been tested for their HBsAg status during the antenatal period. If a woman’s HBsAg status is unknown at the time of delivery, the baby should be given hepatitis B vaccine at the time of delivery while waiting for the result of an urgent HBsAg test on the mother. If she is found to be HBsAg positive, the baby should be given HBIG as soon as possible, up to seven days post-delivery.29 Subsequent vaccine doses are given as per the Schedule.

It is essential to take blood to determine whether the baby has seroconverted (anti-HBs positive) or has become infected despite immunoprophylaxis (HBsAg positive), or is neither infected nor immune (ie, HBsAg negative and anti-HBs negative). Testing should not be performed before 9 months of age to avoid detection of anti-HBs from HBIG administered during infancy and to maximise the likelihood of detecting late HBV infections.29

Babies of HBsAg-positive mothers should be placed on a practice recall system to have their blood tested at 9 months of age, and should be rechecked at the 15-month immunisation event to ensure that testing has occurred. The serology results should be interpreted as in Figure 8.2.

The National Immunisation Register (NIR) collects data (with parental consent) on those babies who receive HBIG and hepatitis B vaccine at birth.

Figure 8.2: Management of a baby of an HBsAg-positive woman

Screen all women in early pregnancy for hepatitis B carriage

Woman is HBsAg positive No  Figure 8.2: arrow1   See ‘Infants’ in section 8.5.2
Yes
Figure 8.2: arrow2
All HBsAg-positive pregnant women should also be tested for HBeAg and should have HBV DNA measured. The results should be discussed with a specialist or, early in her pregnancy, the woman should be referred to a specialist for ongoing care. Give the baby hepatitis B protection as follows.
At age Action to be taken
Birth Give hepatitis B immunoglobulin 100–110 IU neonatal and hepatitis B vaccine 5 µg
6 weeks DTaP-IPV-HepB/Hib
3 months DTaP-IPV-HepB/Hib
5 months DTaP-IPV-HepB/Hib
9 months Take a blood test to check for hepatitis B infection (HBsAg) and for vaccine-induced immunity (anti-HBs).
  • If HBsAg is negative and anti-HBs level is ≥10 IU/L* at age 9 months, immunity is proven.
  • If HBsAg is positive, the baby has become infected despite prophylaxis: refer to an appropriate specialist.
  • If HBsAg is negative and anti-HBs level is <10 IU/L* at age 9 months, give a further 3 doses of hepatitis B vaccine at least 4 weeks apart. Recheck serology 4 weeks after the last dose. If there is no seroconversion after the third further dose of hepatitis B vaccine (ie, if anti-HBs is still <10 IU/L*), discuss with a specialist.
All other vaccines should be administered as per the Schedule.
Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments. See the note in section 8.5.5.

Neonatal HBIG plus vaccine will fail to prevent vertical HBV transmission in more than 20 percent of infants born to HBsAg-positive mothers with serum HBV DNA levels greater than 108 IU/mL (or 108 copies/mL). These mothers are usually young, with normal alanine transaminase (ALT), and are HBeAg positive. If the mother’s HBV DNA level is greater than 108 IU/mL, administration of tenofovir (an antiviral agent) during the last trimester is also recommended and funded.

The number of such high-risk pregnancies appears to be increasing in this country as a result of the immigration of young Asian women of childbearing age, of whom an estimated 8 percent are HBsAg positive, with the majority also HBeAg positive. In contrast, the number of HBsAg-positive Māori and Pacific women of childbearing age has decreased markedly due to infant vaccination. In addition, most HBsAg positive Māori and Pacific women are HBeAg negative, with lower HBV DNA levels (below 108 IU/mL).

Babies born to mothers who received oral antiviral therapy for chronic HBV must still receive the recommended neonatal HBIG/vaccine schedule. All other vaccines are administered as per the Schedule.

See sections 1.5 and 8.8.1 for more information about passive immunisation and HBIG.

Pregnancy and breastfeeding

Hepatitis B vaccine may be given during pregnancy and while breastfeeding. Acute hepatitis B infection in pregnant women may result in severe acute hepatitis for the mother, with associated increased risk of fetal loss or neonatal infection. Vaccination should not be withheld from a susceptible pregnant woman at increased risk of acquiring hepatitis B (eg, the sexual partner of an injecting drug user, or known infected male).

Preterm and low birthweight infants

Infants of HBsAg-positive women

Preterm and low birthweight infants of HBsAg-positive women should be managed as above, regardless of birthweight or gestation.

Preterm infants of HBsAg-negative women

Infants of HBsAg-negative women who were born at less than 37 weeks’ gestation, or who are less than 2000 grams should be vaccinated as per the usual childhood schedule above (at ages 6 weeks, 3 and 5 months) and follow-up serological testing is not indicated.

Some low birthweight or preterm infants may have a reduced response to hepatitis B vaccine at birth.30 However, by the chronological age of 1 month, all medically stable preterm infants, regardless of initial birthweight or gestational age, are as likely to respond to hepatitis B vaccine as are term and larger infants.29 Because New Zealand’s Schedule starts at age 6 weeks, low birthweight and preterm infants are expected to respond to hepatitis B vaccine.

Adult dialysis or adult liver or kidney transplant patients

These adults may have a reduced response to hepatitis B vaccine, so the higher-dose (40 ug) formulation is recommended and funded. See also section 8.5.5 for information about post-vaccination serology.

Management of blood and body fluid exposures (BBFE)

Recommendations following a needle-stick injury are covered in Appendix 7, but the principles relating to hepatitis B are as follows.

No specific intervention is required for hepatitis B.
If the recipient has a history of being vaccinated (with three documented doses) but has anti-HBs Ab <10 IU/L,* give another dose of hepatitis B vaccine and check serology 4 weeks later – unless they have ever previously had a recorded anti-HBs Ab ≥10 IU/L.*
– ​If recipient has been incompletely vaccinated but has had two doses more than four months previously, give a third dose.
– If the recipient was previously vaccinated and is anti-HBs Ab <10 IU/L,* give another dose of hepatitis B vaccine and HBIG as soon as possible.
If the recipient was not previously vaccinated, give HBIG and commence the three-dose vaccination course.
– ​If the recipient has been incompletely vaccinated, give the next vaccine dose and HBIG.
No specific intervention is required in this case. However, vaccination would often be indicated on the basis that the recipient is at higher risk, as demonstrated by being exposed on this occasion.
Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments. See the note in section 8.5.5.

8.5.4 (Re-)vaccinationTop

Hepatitis B-containing vaccines are funded for (re-)vaccination of eligible individuals, as follows.

DTaP-IPV-HepB/Hib (Infanrix-hexa) is funded for children aged under 10 years: 

Hep B (HBvaxPRO) is funded for individuals following immunosuppression. 

See also section 4.3.

8.5.5 Serological testingTop

Note: Serum anti-HBs antibody ≥10 IU/L is the WHO measure of immunity. Unfortunately, routine laboratory tests do not give consistent results <20 IU/L. There may therefore be variations between laboratories for the antibody level at which an individual is considered to be immune. Please follow the testing laboratory’s interpretative comments.

Serological markers of infection

The antigens described in section 8.1 and their associated antibodies are serological markers of HBV infection or vaccination. At least one serological marker is present during the different phases of infection (Table 8.3). The antigens and their respective antibodies include:

Antigen Antibody
HBsAg
(hepatitis B surface antigen)
Anti-HBs (antibody to HBsAg),
(IgM, IgG, and total)
HBcAg
(hepatitis B core antigen)
Anti-HBc (antibody to HBcAg),
(IgM, IgG and total)
HBeAg
(hepatitis B e antigen)
Anti-HBe (antibody to HBeAg),
(IgM, IgG and total)

Table 8.3: Interpretation of serology for hepatitis B virus infection

Serological marker Interpretation
HBsAg Total
anti-HBc
IgM
anti-HBc
Anti-HBs  
Never infected
+ + + Acute infection
+ + + or – Acute resolving infection
+ + Recovered from past infection and is immune
+ + Chronic infection
+ Immune if concentration is ≥10 IU/L.* Vaccinated or natural infection.

Key: Anti-HBc = antibody to hepatitis B core antigen; anti-HBs = antibody to hepatitis B surface antigen (HBsAg); IgM = immunoglobulin M; = positive test result; – = negative test result.

* Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.

Source: Adapted from: Van Damme P, Ward J, Shouval et al. 2013. Hepatitis B vaccines. In: Plotkin SA, Orenstein WA, Offit PA (eds). Vaccines (6th edition). Elsevier Saunders, Table 15.1.

See the Communicable Disease Control Manual 201231 for recommendations for HBV case and contact management.

Pre-vaccination screening: screening for chronic infection

Screening should be part of the informed consent procedure before administering hepatitis B vaccine (see sections 2.3 and 8.3.2), other than in infancy and early childhood. The purpose of pre-vaccination screening is to avoid giving vaccine to those who are chronically HBV infected or are already immune.

In general, those at higher risk of chronic HBV infection should be encouraged to undergo pre-vaccination screening, while those at low risk may be vaccinated without prior screening. Vaccinating a person who is chronically HBV infected does not prevent the future diagnosis, nor does it cause an increase in adverse reactions. Globally, pre vaccination serological testing is not recommended as routine practice.

Pregnancy

All pregnant women should receive antenatal screening for hepatitis B infection by testing for HBsAg. All HBsAg-positive pregnant women should also be tested for HBeAg and have their HBV DNA level measured early in pregnancy. A referral to a specialist with an interest in hepatitis B and/or the high-risk obstetric team should be made, because anti-viral treatment maybe indicated. Infants of HBsAg-positive mothers should be given hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine as close as possible to birth, preferably within 12 hours. HBIG can only be given up to seven days post-delivery (see section 8.5.3). Babies born to mothers who received oral antiviral therapy must still receive the recommended neonatal HBIG/vaccine schedule (see section 8.5.3). All other vaccines are administered as per the Schedule.

Other high-risk groups

Adults in population groups at high risk of chronic HBV infection (eg, Māori, Pacific and Asian people; see the Hepatitis Foundation recommendations in section 8.3.2) should be screened for chronic HBV infection. All identified HBsAg-positive individuals can be offered counselling about the risks of transmission to others and the importance of avoiding or minimising other causes of liver damage, such as excessive alcohol consumption. All HBsAg-positive individuals should be offered follow-up under the Hepatitis Foundation Hep B Follow-up Programme to enable early diagnosis and treatment of the complications of severe liver disease and hepatocellular carcinoma (HCC). Vaccination is recommended (and funded) for household or sexual contacts of HBsAg-positive people (ie, people with acute or chronic HBV infection).

Testing post-vaccination

Routine measurement of anti-HBs antibody levels after vaccination is not normally recommended. The exception may be for those at increased risk of disease, in which case seroconversion should be demonstrated. Such groups include:

For previously vaccinated individuals at increased risk without a documented seroconversion, it is recommended that a booster dose of hepatitis B vaccine be given and antibodies measured four weeks later. Most vaccinees will develop a high anti-HBs titre, usually greater than 100 IU/L. If they do not achieve a titre of greater than or equal to 10 IU/L,* they should be considered a non-responder and receive two further doses of hepatitis vaccine, four weeks apart, to complete a second course of three vaccine doses. Repeat the serology four weeks after the final vaccine dose. See the non-responders section below if, after the second course of three vaccines, they have not achieved an anti-HBs titre of ≥10 IU/L.* 

Recently vaccinated individuals at increased risk of disease are advised to have serology for anti-HBs a minimum of four weeks after their third documented hepatitis B vaccine. If they do not achieve a titre of greater than or equal to 10 IU/L* they should be considered a non-responder and receive three further doses of hepatitis vaccine, four weeks apart, to complete a second course of three vaccines. Repeat the serology four weeks after the final vaccine dose. See the non-responders section below if, after the second course of vaccines, they have not achieved an anti-HBs titre of ≥10 IU/L.* 

Vaccinated individuals who have at any time had anti-HBs ≥10 IU/L do not need any booster doses, even if antibodies subsequently wane to undetectable levels, which occurs in most individuals by seven years after the last vaccination. If exposed, they will have a secondary anamnestic immune response that will prevent replication of the virus.1, 41

* Some laboratories may require a higher anti-HBs antibody level for proof of immunity. Please follow the testing laboratory’s interpretative comments.
Non-responders to vaccination

Persistent non-responders with no immunodeficiency who have completed the primary series and a full second course of three vaccine doses should be monitored for wild-type disease, but literature reports of vaccine failures are rare. They should be considered ‘unprotected’ against hepatitis B and advised to minimise the chance of exposures. Parenteral or mucosal exposure to HBV requires HBIG within 72 hours.

An intradermal injection of reduced doses of routine hepatitis B vaccine,42, 43 intramuscular injection of double doses of routine hepatitis B vaccine44, 45 and intramuscular injection of double doses of combined hepatitis A and B vaccine46 have all been shown to stimulate protective responses in a proportion of individuals who have not responded to a three-dose series, but it is not possible to recommend one approach over the others.