Hepatitis B

What

Hepatitis B is an infection caused by hepatitis B virus that affects the liver. Hepatitis B virus may be transmitted by inoculation through broken or penetrated skin, or by mucosal contact with blood or other body fluids (mainly vaginal fluids and semen) from an infectious person.

Who

Hepatitis B vaccination is recommended for:

• infants
• Aboriginal and Torres Strait Islander people
• people who are immunocompromised, including people
  • with HIV
  • with severely impaired renal function
  • on dialysis
  • before solid organ transplant
  • after haematopoietic stem cell transplant
• people with medical risk factors, including
  • people with hepatitis C
  • people with chronic liver disease
  • preterm and low-birthweight infants
  • people who receive blood products
  • people with developmental disabilities
• people whose occupation increases their risk of acquiring hepatitis B, including
  • healthcare workers
  • police, members of the armed forces, emergency services staff and staff of correctional facilities
  • staff of facilities caring for people with developmental disabilities
  • funeral worker and embalmers
  • tattooists and body-piercers
• travellers to hepatitis B–endemic areas who may be at increased risk
• people whose circumstances increase their risk of acquiring hepatitis B, including
  • infants born to mothers who are hepatitis B surface antigen–positive
  • household or other close contacts of people with hepatitis B
  • sexual contacts of people with hepatitis B
  • men who have sex with men
  • migrants from hepatitis B–endemic countries
  • people who inject drugs
  • inmates of correctional facilities
  • sex industry workers

How

Hepatitis B vaccination is recommended for infants and children in a 4-dose schedule at birth, and 2, 4 and 6 months of age.

Hepatitis B vaccination is recommended for all other risk groups, usually in a 3-dose schedule (0, 1 and 6 months). Adolescents aged 11–15 years can receive an alternative 2-dose schedule at 0 and 6 months.

Why

After acute infection with hepatitis B virus, some people become chronically infected. For those whose infection resolves, the virus remains in latent form in liver cells and can reactivate. People with chronic hepatitis B can transmit the disease, including from mother to child. Chronic hepatitis B is associated with death from cirrhosis or hepatocellular carcinoma in up to 25% of cases.

Hepatitis B vaccines available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Dose and route

The dose of Engerix-B and H-B-Vax II (paediatric formulations) and Twinrix Junior (360/10) is 0.5 mL given by intramuscular injection.

The dose of Engerix-B and H-B-Vax II (adult formulations) and Twinrix (720/20) is 1.0 mL given by intramuscular injection.

The dose of Infanrix hexa and Vaxelis is 0.5 mL given by intramuscular injection.

The schedules for hepatitis B vaccines are shown in:

• Table. Monovalent hepatitis B vaccines for adolescents and adults
• Table. Accelerated hepatitis B vaccination schedules for people with imminent risk of exposure
• Table. Combination hepatitis A-hepatitis B vaccines (see also Hepatitis A)

Co-administration with other vaccines

People can receive hepatitis B and combination hepatitis A-hepatitis B vaccines at any time before or after, or with, most other vaccines.

Infants and children can receive hepatitis B vaccines at the same time as other immunisation products (such as oral or intramuscular vitamin K, hepatitis B immunoglobulin and RSV monoclonal antibodies). Because vaccines target specific antigens, there is unlikely to be any interference with other disease antigens from other immunisation products.

Vaxelis can be given at the same time as other scheduled vaccines, including MenB vaccines.

Interchangeability of hepatitis B vaccines

The Engerix-B and H-B-Vax II vaccines are manufactured by different processes, and the hepatitis B surface antigen content of an ‘equivalent’ dose of these vaccines is different. Switching vaccine brands is not recommended.

If possible, complete the vaccination schedule for Infanrix hexa and Vaxelis with the same vaccine brand. If this is not possible, use an alternative brand following the dose recommendations. See Recommendations - Infants are recommended to receive 4 doses of hepatitis B vaccine.

If the brand of vaccine used for previous doses is not known, use another age-appropriate ‘equivalent’ dose brand. See:

• Hepatitis B vaccines available in Australia
• Table. Monovalent hepatitis B vaccines for adolescents and adults

For example, a study in healthy neonates showed comparable high levels of immunogenicity between 2 different mixed regimens that used 2 monovalent hepatitis B vaccines from different manufacturers.³³

Hepatitis B immunoglobulin (HBIG) is prepared from plasma donated through routine blood bank collection. Samples are selected based on their high levels of antibody to hepatitis B surface antigen.

Stocks of HBIG are very limited, so HBIG should be strictly reserved for people who are at high risk, such as:

• babies born to mothers with chronic hepatitis B virus infection
• people who are non-immune and are occupationally exposed to the blood of unidentified people
• people who are chronically infected with hepatitis B virus or whose hepatitis status cannot be determined in time³⁴

Request HBIG from the Australian Red Cross Blood Service in your state or territory.

Contraindications

Hepatitis B vaccines are contraindicated in people who have had:

• anaphylaxis after a previous dose of any hepatitis B vaccine
• anaphylaxis after any component of a hepatitis B vaccine
• anaphylaxis to yeast

Precautions

Women who are pregnant or breastfeeding

Hepatitis B vaccine is not routinely recommended for pregnant or breastfeeding women.

However, the World Health Organization states that pregnancy and breastfeeding are not contraindications for hepatitis B vaccination. ³⁴

See Table. Vaccines that are not routinely recommended in pregnancy: inactivated viral vaccines in Vaccination for women who are planning pregnancy, pregnant or breastfeeding for more details.

People with latex allergy

The product information for H-B-Vax II states that the vial stopper, syringe plunger stopper and tip cap of the syringe contain latex. Consider using an alternative product in people with an allergy or sensitivity to latex.

Newborns

Newborns tolerate the birth dose of hepatitis B vaccine very well. The vaccine does not interfere with either establishing or maintaining breastfeeding. In newborns who were vaccinated compared with unvaccinated infants, the vaccine is not associated with an increased risk of: ^35-37

• fever (occurs in 0.6–3.7% of neonates)
• medical investigation for sepsis
• serious outcomes

Adults

Adverse events after hepatitis B vaccination are transient and minor, and include:²²

• soreness at the injection site (5%)
• fever (usually low grade; 2–3%)
• nausea
• dizziness
• myalgia
• arthralgia

Anaphylaxis is reported very rarely in adults, usually in yeast-sensitive individuals.³⁸ Various adverse events such as demyelinating diseases, Guillain–Barré syndrome and arthritis have been reported, but there is no evidence that hepatitis B vaccination causes these.^38,39

The World Health Organization Global Advisory Committee on Vaccine Safety states that ‘multiple studies and review panels have concluded that there is no link between multiple sclerosis and hepatitis B vaccination’.^40,41

Combination vaccines

Local and systemic adverse reactions are more common after hexavalent vaccines than after monovalent vaccines. There is little to no difference in the rates of adverse events after hexavalent vaccines compared with other combination vaccines including other hexavalent vaccines.^42-44 

People with chronic hepatitis B

The vaccine does not affect people with chronic hepatitis B virus infection — there are no therapeutic benefits or associated adverse events. The vaccine is also safe in people who are already immune to hepatitis B through past natural infection, but it offers no additional benefit.

Hepatitis B is an infection caused by hepatitis B virus. It affects the liver.

Pathogenesis

The incubation period is usually 45–180 days. The period of communicability starts from several weeks before the onset of acute illness, and usually lasts 4–5 months while hepatitis B surface antigen (HBsAg) is present. People with chronic infection usually remain infectious for life.

Transmission

Hepatitis B virus may be transmitted by inoculation through broken or penetrated skin, or by mucosal contact with blood or other body fluids (mainly vaginal fluids and semen) from an infectious person. The 3 major routes of hepatitis B virus transmission are:

• perinatal
• parenteral
• mucosal (often sexual)

Perinatal transmission

Perinatal transmission occurs from infected the mother to the neonate usually at, or around the time of birth. This is also called vertical transmission.

Parenteral exposure to infected blood and other body fluids

Examples of parenteral transmission include:

• exposure to contaminated equipment that penetrates the skin, such as needles (among people who inject drugs), tattoo equipment, medical or dental equipment if there is poor infection control, body-piercing equipment, acupuncture equipment and razor blades
• needlestick injury, such as in a healthcare setting
• household transmission, such as child-to-child transmission through contact between open sores or wounds

In Australia, blood and organ donors are screened for hepatitis B virus using serological and nucleic acid amplification testing. This has nearly eliminated the risk of transmission of hepatitis B through blood transfusion and organ transplants.^45,46

Mucosal exposure to infected blood and other body fluids

Mucosal exposure occurs when there is contact between infective body fluids and mucous membranes.

Sexual contact includes vaginal and anal intercourse. Anal sex is associated with a higher risk.

Saliva may be infective only if inoculated directly into tissue (ocular or mucous membranes).

The risk of transmission by inadvertent inoculation by other means is low but not negligible. Transmission could be by:^47-54

• sharing a toothbrush, razor or similar
• close personal contact in households that have 1 or more infected people

Laboratory diagnosis

Hepatitis B virus infection is diagnosed by serological testing. Hepatitis B serology allows clinicians to determine susceptibility, active infection, or immunity through vaccination or past infection. The following markers are tested for:

• HBsAg — acute infection
• antibody to HBsAg (anti-HBs) — immunity from immunisation or infection
• antibody to hepatitis B core antigen (anti-HBc) — acute or chronic infection

Acute hepatitis B

Hepatitis B virus infection causes symptomatic acute hepatitis in approximately 30–50% of adults. In neonates and young children, particularly those <1 year of age, the initial infection is usually asymptomatic.^56,57

Acute hepatitis B is clinically indistinguishable from other forms of hepatitis. Symptoms of hepatitis include: ^58,59

• fever
• jaundice
• malaise
• anorexia
• nausea 
• vomiting
• abdominal pain (especially in the right upper quadrant)
• myalgia
• dark-coloured urine 
• light-coloured stools
• arthralgia 
• arthritis 
• rash

During recovery, malaise and fatigue can last for many weeks.

Fulminant hepatitis occurs in up to 1% of acute cases.^58,59

Chronic hepatitis B

Some people become chronically infected with hepatitis B virus after acute infection. This happens in about 1–10% of people infected in adulthood,^,57,60 but up to 90% of people infected in early infancy.⁶⁰ People chronically infected with hepatitis B virus have circulating hepatitis B surface antigen for >6 months.^58,59 

People with chronic hepatitis B virus infection can transmit the disease, including from mother to child. These people are often asymptomatic and may not be aware that they are infected.

Chronic hepatitis B virus infection is associated with most of the serious complications. Chronic hepatitis B is associated with death from cirrhosis and/or hepatocellular carcinoma in up to 25% of cases.⁵⁸

People with occult infection may reactivate hepatitis B virus infection if they become immunocompromised.

Hepatitis B in Australia

Hepatitis B remains the most common blood-borne viral infection in Australia. The estimated prevalence of chronic hepatitis B in 2020 was 0.9%. Populations most affected by hepatitis B within Australia are Aboriginal and Torres Strait Islander people and those born overseas.^61-64

Since the introduction of funded universal infant hepatitis B immunisation, Australia has seen a three-fold decline in the rate of newly acquired hepatitis B notifications between 2000 and 2019.⁶⁵ There were 4,945 notifications reported during this period (average annual rate 1.13 per 100,000 population per year). Similarly, between 2001 and 2019 annual hospitalisation rates have halved.⁶⁵ Between 2000 and 2019, there were 253 deaths reported where acute hepatitis B was the underlying cause of death. There were no deaths reported among people born after May 2000.

The average annual notification rate was highest among young adults aged 25–29 years and lowest among young children <10 years of age.⁶⁵ Notification rates and mortality were three-fold higher in males compared to females. Although notification rates have halved among Aboriginal and Torres Strait Islander people, both notification and hospitalisation rates remain higher than other people.⁶⁵

Of the notifications where country of birth was known, 75% of newly acquired hepatitis B were in people born in Australia and the vast majority (93%) were acquired within Australia, with a small proportion (3%) acquired in South-East Asia.⁶⁵ More than two-thirds of people living with chronic hepatitis B in Australia were born (and likely acquired hepatitis B) overseas.⁶⁴

Hepatitis B Globally

The World Health Organization estimates that 296 million people were living with chronic hepatitis B infection in 2019, with 1.5 million new infections each year. In 2019, hepatitis B resulted in an estimated 820,000 deaths, mostly from cirrhosis and hepatocellular carcinoma (primary liver cancer).⁶⁶ The burden due to chronically infected people is highest in the WHO Western Pacific Region (116 million) and the WHO African Region (81 million). This is followed by the WHO Eastern Mediterranean Region (60 million), the WHO South-East Asia Region (18 million), the WHO European Region (14 million) and the WHO Region of the Americas (5 million).⁶⁶

 

Hepatitis B vaccines are prepared using recombinant technology. After purification, the hepatitis B surface antigen (HBsAg) protein is adsorbed onto elemental aluminium (as hydroxide and/or phosphate). Hepatitis B vaccines may contain up to 1% yeast proteins (but no yeast DNA).

The Engerix-B and H-B-Vax II vaccines are manufactured by different processes, and the HBsAg content of ‘equivalent’ doses of these 2 vaccines is different. The HBsAg content of the paediatric formulations of these 2 vaccines is half that of the corresponding manufacturer’s adult formulation.

Hepatitis B vaccines have been studied using different schedules and intervals for different age groups. Acceptable schedules are shown in the following tables and described in this section:

• Table. Monovalent hepatitis B vaccines for adolescents and adults
• Table. Accelerated hepatitis B vaccination schedules for people with imminent risk of exposure
• Table. Combination hepatitis A-hepatitis B vaccines (see also Hepatitis A)

Standard 3-dose schedule and variations

In clinical trials for DTPa-hepB-Hib-IPV vaccines, 3-dose schedules given at 2, 4 and 6 months of age were immunogenic, with more than 97% of children in the Infanrix hexa trial and 100% of children in the Vaxelis trial developing protection to hepatitis B antigen.⁶⁷

A 3-dose schedule at birth, 1–2 months and 6–18 months of age is equally as immunogenic as the recommended Australian schedule above. Such schedules are often used overseas.^68-70 Children born overseas who have received hepatitis B vaccine in this 3-dose schedule are considered to have completed the vaccination course.

Longer intervals between doses do not affect the immunogenicity of hepatitis B vaccine.^71,72 The minimum interval between the 1st and 3rd doses of a 3-dose schedule is 4 months. This means that a shortened 3-dose schedule provided at either 0, 1, 4 months or 0, 2, 4 months is acceptable.²²

A standard 3-dose schedule induces protective levels of neutralising antibody against hepatitis B virus in more than 90% of healthy adults.⁷³ Seroconversion occurs in approximately 30–55% of people after the 1st dose, increasing to 75% of people after the 2nd dose. The 3rd dose is needed to increase the percentage of people who respond and to provide long-term protection.^73,74

More compressed 3-dose schedules, such as 0, 1, 3 months, are not recommended. These compressed schedules are associated with:

• lower peak levels of antibody to hepatitis B surface antigen (anti-HBs)^75,76 
• likely shorter duration of antibody persistence at levels of ≥10 mIU per mL⁷⁷

The clinical significance of this is uncertain.⁷⁸

If a person has already received a compressed 3-dose schedule that does not meet the minimum intervals, they may not need to repeat a dose. Most people who have undetectable anti-HBs mount an anamnestic response to an additional vaccine dose. This indicates they are likely to be protected if exposed to hepatitis B virus.⁷⁸

The proportion of vaccine recipients attaining seroprotective anti-HBs levels (≥10 mIU per mL) is comparable between adults who received their 3rd dose at 4–6 months after the 1st dose and those who received their 3rd dose 6 months or more after the 1st dose.⁷⁹

Accelerated schedules

The interval between the 1st and 3rd doses has been shortened to <4 months in studies of 4-dose accelerated schedules. The aim is to achieve a higher seroprotective antibody level sooner.

A high proportion of vaccine recipients attain seroprotective anti-HBs levels (≥10 mIU per mL) in the early months after starting an accelerated schedule. However, antibody levels are substantially lower 7 months after an accelerated 3-dose schedule than after the standard 3-dose schedule.⁸⁰

Also, some studies have shown a lower proportion of people attaining the seroprotective antibody level after 3 doses of an accelerated schedule than after the standard 3-dose schedule.^80-82

An accelerated schedule requires a 4th dose at 12 months. After this dose, anti-HBs antibody levels are higher than, or comparable to, those after a standard 3-dose schedule.

Alternative 2-dose schedule for adolescents

Adolescents 11–15 years of age can receive 2 doses of adult-formulation monovalent hepatitis B vaccine 4–6 months apart. This may improve compliance in this age group, and provides comparable immunity to the 3-dose paediatric schedule.^83-85

Transport according to National Vaccine Storage Guidelines: Strive for 5.⁸⁶ Store at +2°C to +8°C. Do not freeze. Protect from light.

Infanrix hexa must be reconstituted. Add the entire contents of the syringe to the vial and shake until the pellet completely dissolves. Use reconstituted vaccine as soon as practicable. If it must be stored, hold at room temperature for no more than 8 hours.

Acute hepatitis B and newly identified chronic hepatitis B are notifiable diseases in all states and territories in Australia.

The Communicable Diseases Network Australia national guidelines for hepatitis B⁸⁷ have details about the management of hepatitis B cases and contacts.

State and territory public health authorities can provide further advice about the public health management of hepatitis B.

Post-exposure vaccine and immunoglobulin

If an exposed person is non-immune, they will be negative for antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc). If they are exposed to a source who is either positive for hepatitis B surface antigen (HBsAg) or cannot be identified and tested rapidly, the non-immune person who was exposed should receive a single dose of hepatitis B immunoglobulin (HBIG) according to Table. Post-exposure prophylaxis for non-immune people exposed to a source that is positive for hepatitis B surface antigen or has an unknown status. They should also receive hepatitis B vaccine as soon as possible, with further doses as recommended in Table. Post-exposure prophylaxis for non-immune people exposed to a source that is positive for hepatitis B surface antigen or has an unknown status.

Previously vaccinated people do not need post-exposure prophylaxis if they had a documented protective response (anti-HBs level of ≥10 mIU per mL) at any time after vaccination.

If the response to previous vaccination is unknown, determine the anti-HBs level as quickly as possible. If the anti-HBs level is <10 mIU per mL and there is no evidence of hepatitis B virus infection, the person exposed should receive HBIG and hepatitis B vaccine according to Table. Post-exposure prophylaxis for non-immune people exposed to a source that is positive for hepatitis B surface antigen or has an unknown status.

Post-exposure vaccine for healthcare workers

Non-immune healthcare workers who have had a needlestick injury or other potential hepatitis B exposure are recommended to receive a full course of hepatitis B vaccine. All healthcare workers should be immunised against hepatitis B.

Routine vaccination in children and adults

Infanrix Hexa

The product information for Infanrix hexa states that this vaccine is for:

• primary immunisation of infants from the age of 6 weeks
• booster dose for children 18 months of age if they need boosting for all antigens

The Australian Technical Advisory Group on Immunisation (ATAGI) recommends that Infanrix hexa may also be used for catch-up of the primary schedule or as a booster in children <10 years of age.

Vaxelis

The product information for Vaxelis states that this vaccine is for:

• primary immunisation of infants from the age of 6 weeks
• a booster dose at least 6 months after the last priming dose

ATAGI recommends that Vaxelis may also be used for catch-up of the primary schedule or as a booster in children <10 years of age.

Contraindications

The product information for Infanrix hexa and Vaxelis states that this vaccine is contraindicated in children with either:

• encephalopathy of unknown aetiology, or
• neurologic complications occurring within 7 days after a vaccine dose

ATAGI recommends that the only contraindications are:

• anaphylaxis to a previous dose
• anaphylaxis to any of the vaccine components

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