Hepatitis A virus (HAV) is one of the most common vaccine-preventable diseases in the world with an incidence of 1.5 million cases per year worldwide.¹ An epidemic was described by Hippocrates in the fifth century BC, but not until 1979 was the single stranded RNA virus (of the Picornaviridae family) grown in a laboratory. There is no specific treatment and the first effective vaccine was introduced in 1992.

Hepatitis A infection is common in less developed countries where hygiene is poor. Spread is mainly by the faecal-oral route but also by person-to-person contact (although food and drink contamination may be involved). The infection can be silent, especially in children, and the hepatitis can be with or without jaundice. Fulminant hepatitis is rare (0.1%). Mortality rises with age from 0.1% in those aged under 4 years to 2% in those aged over 60 years. Recovery may take 6-12 months. There is no chronic carrier state. The increasing pool of susceptible, nonimmune people in developed countries and more foreign travel pose an increasing risk of infection. Older patients are at increased risk of both infection and the serious sequelae from infection.

Hepatitis A vaccine

The vaccines are all formaldehyde inactivated and prepared from virus strains (GBM, HM 175 or RG-SB) grown in human diploid cells. Three (Havrix Monodose®, Vaqta®, Avaxim®) are absorbed on to an aluminium hydroxide adjuvant but Epaxal® contains inactivated virus particles attached to phospholipid vesicles. They can be used interchangeably.

Storage

They are supplied as a slightly opaque suspension (except Epaxal® which is an emulsion, and particle-free) in 0.5-1 ml syringes and storage should be protected from light between 2-8°C. They should not be diluted or mixed. Discard if frozen. Shelf life is 2 years, and 3 years for Avaxim®. Potency of Vaqta® is little affected by exposure to 28°C for 3 months but this is not recommended for storage.

Administration

They should be shaken before use and given into the deltoid region intramuscularly. In cases of severe bleeding diathesis, the subcutaneous route is licensed for Avaxim® and Havrix Monodose®. Other vaccines can be given at the same time, but a different site should be used.

Schedule

• Primary vaccination. This consists of 1 dose of vaccine, correct for age. Seroconversion is 88% at 2 weeks rising to 95% and producing antibodies for up to 1 year.
• Reinforcing dose. This is given 6-18 months after the primary dose depending on which vaccine has been given. Seroconversion is virtually 100% and lasts at least 25 years and possibly a lifetime.^1,2 The reinforcing dose can be delayed for between 3 and 4 years depending on which vaccine is given. For those at continued risk, a further booster at 20 years is now recommended (this used to be 10 years).³

Indications for hepatitis A vaccination

Recommended for those at risk of exposure to hepatitis A virus (HAV) or of complications from getting HAV:

• Travellers to moderate to high-risk areas, i.e. any country outside northern and western Europe, North America, Japan, New Zealand and Australia. The Indian subcontinent carries the highest risk.
• Patients with chronic liver disease including hepatitis B and hepatitis C.⁴
• Haemophiliacs receiving Factor VIII and IX concentrates (subcutaneously).
• Intravenous drug users (with hepatitis B vaccine or using combined vaccine).
• Certain occupations (recommended in laboratory workers likely to be exposed to the virus, staff of large residential institutions, sewerage workers, and workers with primates. It should be considered in food handlers, and for staff in day-care facilities. Military personnel often require vaccination).
• People at risk because of their sexual behaviour (mainly anal intercourse).
• Management of outbreaks of HAV.

Contra-indications to hepatitis A vaccination

• Acute febrile illness, but not minor non-febrile illnesses.
• Previous severe reaction to hepatitis A vaccine.
• Hypersensitivity to components of the vaccine.
• Pregnancy and lactation, unless there is definite risk of infection.
• Children aged under 1 (children aged 1-16 have junior vaccine).

Adverse effects

• Local: mild, transient soreness and redness.
• General: flu-like symptoms.
• Mild, temporary elevation of liver enzymes has been reported.

Combination vaccines

Combinations with hepatitis B (Twinrix®) and typhoid (Hepatyrix®, ViATIM®) have been developed and these may offer advantages of convenience when several vaccines are needed. However, the schedules are slightly different, as are the eligible ages.

• Hepatitis A and hepatitis B combined (Twinrix® and Twinrix® Paediatric):Twinrix® Adult, for age 16 and over - paediatric version for ages 1-15 years. The standard schedule is three doses (1 month later, third 6 months after the first or 0,,7 and 21 days for accelerated schedule).
• Hepatitis A and typhoid combined (Hepatyrix® and ViTIM®): where this is used, a booster of Hepatitis A single antigen vaccine will be required 6-12 months later and a booster of typhoid 3 years later as usual.

Human normal immunoglobulin

Human normal immunoglobulin (HNIG) is prepared from pooled plasma and can be used for more immediate passive immunisation. Antibody levels achieved are lower and last only 4-6 months.

• Can be given with vaccine different site.
• No longer recommended for travel prophylaxis.
• Useful in management of outbreaks.⁵

Outbreaks of hepatitis A

Advice on managing these can be sought from the Health Protection Agency. Vaccination can interrupt outbreaks, as demonstrated in Alaska and Slovakia.

Document references

1. Van Herck K, Van Damme P; Prevention of hepatitis A by Havrix: a review.; Expert Rev Vaccines. 2005 Aug;4(4):459-71. [abstract]
2. Shahidah KN; Hepatitis A vaccines.; Med J Malaysia. 2005 Jul;60 Suppl B:112-5. [abstract]
3. Deptartment of Health; Immunisation against infectious disease - 'The Green Book' (various dates)
4. Shim M, Khaykis I, Park J, et al; Susceptibility to hepatitis A in patients with chronic liver disease due to hepatitis C virus infection: missed opportunities for vaccination.; Hepatology. 2005 Sep;42(3):688-95. [abstract]
5. Crowcroft NS, Walsh B, Davison KL, et al; Guidelines for the control of hepatitis A virus infection.; Commun Dis Public Health. 2001 Sep;4(3):213-27. [abstract]

Internet and further reading

• Guidelines on Hepatitis A, Health Protection Agency (2009)

Acknowledgements