Hepatitis B

Causative Organism

Hepatitis B virus (HBV) is a small double-shelled virus in the class Hepadnaviridae; it contains 3 main antigens:

Hepatitis B surface antigen (HbsAg) – produced in large quantities during infection.
Hepatitis B core antigen (HbcAg) – detected during infection and in asymptomatic carriers.
Hepatitis B e antigen (HbeAg) – indicates increased likelihood of the individual having a contagious infection.

Portal hypertension due to hepatocellular carcinoma secondary to Hepatitis B infection. Courtesy Patricia Walker, MD, Ramsay Clinic Associates, St Paul, MN, USA

Signs, symptoms and Complications

Acute infection

May vary from mild to severe.
In general milder or subclinical in young children with increasing severity with age.
Nausea, fatigue, anorexia, jaundice, fever, pruritis, arthralgia or arthritis are possible.
Rarely, an urticarial rash may develop over the trunk and limbs.
Case reports of arteritis and glomerulonephritis.
Fulminant Hepatitis, which may be fatal (approx 2%).

Complications

A chronic carrier state may develop if the immune response is insufficient to remove the virus and it and it continues to replicate, often for many years. The chronically infected individual often has no history of an acute illness.
Children and infants are highly likely to have a sub-clinical illness but much more likely to become 'carriers' than adults who suffer clinical disease but only rarely become carriers.
Carriers are at risk of developing liver cancer or cirrhosis in mid life. Death from chronic liver disease occurs in 15-25% of chronically infected persons. In patients with severe disease resulting in portal hypertension; hepatomegaly, spider naevi, caput medusae, haemorrhoids and oesophageal varices (with melaena, haematemesis and shock if an upper GI bleed results) may be seen.

Methods of Transmission

Transmitted through close contact with blood, body fluids or excretions of infected person e.g. from cuts and scratches, sharing toothbrushes or sex without a condom (particularly among men who have sex with men (MSM)).
Hepatitis B can be passed from infected 'carrier' mothers to their babies at birth (vertical transmission).
Through use of contaminated needles (used by IV drug users, acupuncturists, medical staff, tattooists, etc).
Through blood transfusions. Blood supplies in developed countries are routinely screened for hepatitis B.

Public Health Significance

More than 2000 million people infected worldwide.
Carrier rates for the disease range from 0.5% in developed countries to 15% in Asia, Africa and the Middle East.
A 70-90% vertical transmission rate if the mother is infected or is a carrier.
Approximately 90% of infections acquired in the first 12 weeks of life develop into a chronic carrier state.
Clearance is estimated to occur in 1-6% of carriers per year.
In developed countries, mortality from fulminant infection is 1%.
Approximately 25% of chronic carriers develop hepatic cirrhosis and hepatocellular carcinoma.

New Zealand Epidemiology

The 1985 National Serum Survey found evidence of past infection in 15 percent of New Zealand children, with generally higher rates in the north and east of the North Island.
Milne, Moyes and others showed that in the eastern Bay of Plenty almost half of the population (60 percent of Maori and 30 percent of Europeans) were infected by 15 years of age.
Prior to vaccination, the lifetime risk of acute icteric hepatitis in this region was 10 percent and the risk of developing the chronic carrier state 9 percent.
According to estimates from New Zealand data, chronic carriers have a 5 percent risk of developing chronic active hepatitis or cirrhosis, with perhaps a 2 percent risk of death. The risks are doubled if hepatitis D (delta) virus infection is also present.
Hepatocellular carcinoma is estimated to occur in approximately 10 percent of male and 5 percent of female HBsAg carriers.
Hepatitis B notifications have declined from about 600 per year in the mid-1980s, when immunisation was introduced, to 61 cases notified in 2003 and 39 cases in 2004 (1.6 per 100,000 population). The change in the number of notifications of hepatitis B may also be because earlier notifications of hepatitis B included chronic carrier states, whereas only acute cases are under surveillance now.
In 2005 there were no cases notified who were less than 15 years of age, and only one case was in the 15–19 years age group.

From the 2006 New Zealand Immunisation Handbook. Ministry of Health

Prevention - Non Immunisation Methods

Personal protection and strict hygiene measures as above, although these will not prevent transmission e.g. from 'carrier' mother to her baby at birth.
Abstinence from sexual intercourse or use of a condom.
Use of auto-disable syringes and appropriate disposal of needles in healthcare, acupuncture and tattooing facilities.
Most health authorities have protocols for accidental exposure and follow-up of persons suspected of being exposed to hepatitis B virus.
Avoidance of IV drug use

Prevention - Immunisation

Hepatitis B vaccine was first used in the USA in 1981; as in many other countries it was at first only used for targeted at-risk populations.
As the need for universal immunisation became more obvious, immunisation schedules have included hepatitis B for all infants and also for other specified groups.
Many developing countries have not instituted a universal hepatitis B immunisation programme.

Vaccine/s and Vaccination

All the hepatitis B vaccines currently available are preparations of recombinant HBsAg. The first recombinant vaccine was developed in 1981.
This protein is produced in large quantities by the insertion of the gene for HBsAg into yeast (Saccharomyces cerevisiae).
This is harvested and purified. A small amount of yeast protein residue remains in the final product.
The recombinant HBsAg is adsorbed onto an aluminium salt, which acts as an adjuvant.
Hepatitis B vaccine preparations may be monovalent (adult and child size doses available), or combination (DTaP-IPV-HepB/Hib, HepB).
The WHO recommends the use of combination vaccines so that the recommended three dose primary course of diphtheria, tetanus and pertussis can be completed concurrently as recommended by the Extended Programme on Immunisation.
Preservatives, including thiomersal, may be added. Hepatitis B vaccines may contain up to 1% yeast protein residue (but no yeast DNA).
Thiomersal-free vaccines are now available and are recommended for administration in newborns and infants, due to theoretical concerns about mercury accumulation and toxicity. Most childhood combination vaccines are thiomersal-free.

Efficacy and Effectiveness

In high-risk groups the efficacy is 85- 95%.
Those who develop antibody levels of at least 10 mIU/ml are considered immune to hepatitis B.
At least 95% of infants, children and adolescents develop protection after 3 doses of vaccine.
Efficacy reduces with age and is 70% for those 60 years of age.
Non-responders to the initial 3-dose course of vaccine will usually produce adequate antibody levels after a further booster dose of vaccine or after another course. Persistent non-responders rarely occur.

Efficacy and Effectiveness

In high-risk groups the efficacy is 85- 95%.
Those who develop antibody levels of at least 10 mIU/ml are considered immune to hepatitis B.
At least 95% of infants, children and adolescents develop protection after 3 doses of vaccine.
Efficacy reduces with age and is 70% for those 60 years of age.
Non-responders to the initial 3-dose course of vaccine will usually produce adequate antibody levels after a further booster dose of vaccine or after another course. Persistent non-responders rarely occur.

Availability

In New Zealand immunisation schedule, the Hepatitis B vaccine is given as the combination vaccine diphtheria, tetanus, whooping cough, polio and Haemophilus influenzae type b. (Infanrix^®-hexa)
There are a number of other vaccines licensed in New Zealand, including:
HAV-Hep B (Twinrix™)
Hepatitis B vaccine (HBvaxPRO^®)
DTwP-Hib-Hep B (Tritanrix™-HB+Hib, GSK)
DTaP-Hep B (Infanrix™-Hep B, GSK)
DTaP-IPV-Hep B (Infanrix^©-penta, GSK)

Dosage and Administration

The combination vaccine DTaP-IPV-Hep B/Hib (Infanrix™-hexa) is given at six weeks, three months and five months.

A three dose primary course is recommended for all infants during their first six months of life.

The WHO recommends the use of combination vaccines where feasible, to allow completion of the three dose primary series of diphtheria, tetanus and pertussis immunisation as recommended globally by the Extended Programme on Immunisation.

In countries where hepatitis B is endemic (prevalence of greater than 2% carriage), a universal birth dose is recommended where such a programme is feasible.

Some countries with low endemnicity (<2% prevalence of carriage) have selected hepatitis B immunisation at birth for high-risk individuals, while other countries are implementing a targeted primary series for high-risk individuals only (e.g. certain occupational groups, injecting drug users, household and sexual contacts of Hepatitis B carriers, infants born to carrier mothers as opposed to mass immunisation.

The WHO recommends a universal 3 dose primary course of immunisations at 4-6 weeks apart for all adolescents aged 10-13 years who have not completed a prior primary course. Some countries extend this recommendation to all individuals aged 0-16 years

Indications and Recommendations

Recommendations vary from country to country.

Primary vaccination

Infants and persons aged 0-16 years

A primary 3-dose course should be given, preferably within the first six months of life when the risk of the development of chronic carrier status is highest.
In addition, universal birth doses are recommended in countries where the prevalence of hepatitis B carriage is greater than 2%, where feasible, as well as targeted birth immunisation for high risk infants (those born to carrier mothers).
Vaccination is recommended for all children and adolescents who have not started or completed a primary course. Ideally this should be completed in early adolescence, before the onset of sexual activity.
NB: All babies of carrier mothers (preterm or term) must be given a birth dose of thiomersal-free monovalent hepatitis B vaccine and HBIG. HBIG reduces viral load immediately.
Boosters are not recommended after a primary course.

Preterm babies

As premature babies may have a reduced immune response to vaccination, babies under 32 weeks’ gestation at birth can either:
- 1. Receive HBIG within 12 hours of birth AND
- 2. Receive vaccine at 0, 2, 4 and 6 months, measure anti-HBs (hepatitis B surface antibody) at 7 months and receive a booster at 12 months if antibody titre is low (less than 10 mIU/mL). The last dose and the antibody test can be delayed until 12 and 13 months respectively if hepatitis B-Hib combination vaccines are used; OR
- 3. Only if the mother is seronegative, delay hepatitis B vaccination and receive a 4-dose schedule beginning at 6 weeks to 2 months, with doses 4-8 weeks apart.
- For very small babies – seek specialist advice.

Interchange ability of vaccines

Switching of brands is not recommended, but in cases where the brand of vaccine used for previous doses is not known, any brand may be used.

Serological confirmation of post-vaccination immunity

Post-vaccination serological testing, 4 weeks after the third dose of hepatitis B, is recommended for persons in the following categories:

Those at significant occupational risk (eg. health-care workers, police and military personnel whose work involves frequent exposure to blood and body fluids);
Those at risk of severe or complicated disease (eg. the immunocompromised and persons with pre-existing liver disease not related to hepatitis B);
Those in whom a poor response to hepatitis B vaccination is expected (eg. haemodialysis patients)
If adequate anti-HBs levels (≥10 mIU/mL) are not reached following the third dose, the possibility of HBsAg carriage should be investigated.
Individuals who are HBsAg negative may produce an immune response after an additional dose or after repetition of the primary course, although persistent non-responders may occur. Persistent non-responders should be informed about the need for HBIG within 72 hours of parenteral exposure to HBV.
Those at significant occupational risk who have a documented history of a primary course of hepatitis B vaccine but in whom seroconversion status is unknown, should be given a single booster dose of the vaccine and tested for anti-HBs levels 4 weeks later.
If antibody level is <10 mIU/mL, give 2 further doses of hepatitis B vaccine according to the catch-up schedule, and re-test for anti-HBs levels at least 3-4 weeks after the last dose.

Management of infants born to hepatitis B carrier mothers

Routine antenatal screening for HBsAg is essential for correct implementation of the strategy to prevent newborn infants from becoming infected with, and therefore carriers of, HBV.
Infants born to HBsAg-positive mothers should be given 100 IU IM of HBIG and a dose of thiomersal-free monovalent hepatitis B vaccine on the day of birth. Administration of HBIG is preferable within 12 hours of birth, and must not be delayed beyond 48 hours after birth.
The first dose of monovalent hepatitis B vaccine should be given at the same time as HBIG but in the opposite thigh. Vaccination should not be delayed beyond 7 days after birth.
A primary course should be completed within the first 6-12 months of life, giving a total of 4 doses.
The possibility of testing to ensure immunity should be considered in this group as well.

Other groups for whom hepatitis B vaccination is recommended

Household and sexual contacts of acute and chronic hepatitis B carriers. Testing before planned vaccination is recommended for such contacts as well as members of families who have migrated from high prevalence countries.
Susceptible (anti-HBs negative) sexual partners of patients with acute hepatitis B should be offered post-exposure HBIG and hepatitis B vaccination as soon as possible. Susceptible (anti-HBs negative) partners of asymptomatic carriers should also be offered vaccination.
Hepatitis B is relatively common in clients of sexual health services and it is recommended that vaccination is offered to susceptible individuals at the time of first attendance.
Dialysis patients, HIV-positive individuals and other immunocompromised adults should be given a larger than usual dose of hepatitis B vaccine. They should be given either (i) 1 mL of normal adult formulation in each arm on each occasion (3 dose course), or (ii) a single dose of dialysis formulation vaccine on each occasion, at 0, 1 and 6 months. After completing the primary course, immunosuppressed individuals should be screened for levels of Anti-HBs every 6-12 months and offered boosters if required. The schedule for such boosters needs to be individually determined by regular anti-HBs screens.
Individuals adopting children from countries where hepatitis B is highly endemic - These children should be tested for hepatitis B; if they are HBsAg positive, all non-immune members of the adoptive family should be vaccinated.
Health care workers, embalmers, tattooists, acupuncturists, embalmers – who may be exposed to blood and body fluids.
Police, armed forces personnel, emergency workers and other essential community services occupations – those who may be exposed to blood and body fluids in the line of duty.
Persons with multiple (more than 4) sexual partners.
The risk of transmission during contact sports is low, but hepatitis B immunisation should still be encouraged.

The following groups should be considered for combination hepatitis A/hepatitis B immunisation:

Healthcare and laboratory workers exposed to faeces and body fluids.
Sex industry workers.
Sexually active men who have sex with men should be vaccinated, unless they are already HBsAg positive or have serological evidence of past or continuing infection. The combined hepatitis A and B vaccine may be appropriate for men who have sex with men, if they are not immune to either disease, as they are at risk from both.
Injecting drug users who have not been infected with hepatitis B should be vaccinated. If their hepatitis A serology is negative, they should be offered a course of combination hepatitis A/hepatitis B vaccine.
Recipients of certain blood products - patients with clotting disorders who receive blood product concentrates may have an elevated risk of hepatitis B virus infection, and they should therefore be vaccinated. Screening of blood supplies for hepatitis B has reduced transmission in many countries.
Individuals with chronic liver disease and/or hepatitis C. Hepatitis B vaccination is recommended for those in this category who are seronegative for hepatitis B. Hepatitis A vaccination is also recommended as these individuals have increased morbidity and mortality with hepatitis A infection.
Residents and staff of facilities for persons with intellectual disabilities, both residential and non-residential.
Inmates and staff of long-term correctional facilities –due to the prevalence of homosexual intercourse, injecting drug use and amateur tattooing in some correctional facilities. They should be screened upon incarceration, and vaccinated if susceptible.
Non-immune travellers or emigrants to highly endemic areas – due to the risk to travellers of hepatitis A, combination immunisation should be considered. Travellers planning any form of contact with local residents in highly endemic areas, as well as those planning to reside in such areas long-term should complete vaccination before travel. The risk of contracting hepatitis B, to short-stay business travellers or those who stay in resorts, is low.

Post-exposure prophylaxis for hepatitis B

The recommendations below are a guide only.

Following significant exposure (percutaneous, ocular, or mucous membrane) to blood or potentially contaminated secretions or body fluids, the source individual should be tested for HBsAg and anti-HBs as soon as possible.
If the person exposed is anti-HBs negative, and the source is either HBsAg positive, or cannot be identified and tested rapidly, administer a single dose of HBIG of 100 IU for children up to 30 kg weight (about 5 years of age) and 400 IU for all others, within 72 hours. Also give hepatitis B vaccine (by IM injection into either the deltoid or anterolateral thigh) as soon as possible, but within 7 days of exposure. Two further doses of vaccine should be given, at 1 month and 6 months after the first dose.
For previously vaccinated persons exposed to either an HBsAg positive source or a source whose hepatitis B status cannot be determined, post-exposure prophylaxis is not necessary if there was a documented protective response (anti-HBs level ≥10 mIU/mL) following vaccination. If the response to previous vaccination is unknown, or the anti-HBs is <10 IU/mL, HBIG and vaccine should be administered as above.

For New Zealand Indications and Recommendations refer to the New Zealand Immunisation Handbook.

Adverse Events

Adverse events after hepatitis B vaccination are transient and minor; they include soreness at the injection site (5%), fever (2 to 3%, usually low grade), nausea, dizziness, malaise, myalgia and arthralgia.
Fever can be expected in 0.6 to 3.7% of neonates immunised with hepatitis B vaccine.
Anaphylactoid reactions occur at a rate of 1 in 600,000 doses.
Some case reports of thrombocytopenia, myalgia and arthralgia following hepatitis B immunisation.
No association has been found between hepatitis B immunisation and cancer, type 1 diabetes, multiple sclerosis, encephalomyelitis and pattern baldness.

Contraindications

Anaphylactic reaction to a previous dose or to any vaccine component.
Hepatitis B immunisation is ineffective in HBsAg-positive individuals.

Link to Immunisation Handbook (2006) Chapter 3 - Hepatitis B

Printed from the Immunisation Advisory Centre (IMAC) NZ web site on Thursday, 9 September 2010 11:58:25 p.m..
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