Approximately 1.5 million clinical cases of hepatitis A occur worldwide annually but the rate of infection is probably as much as ten times higher. The incidence rate is strongly related to socio-economic indicators and access to safe drinking water: as incomes rise and access to clean water increases, the incidence of hepatitis A virus (HAV) infection decreases.
An epidemic was described by Hippocrates in the fifth century BC; however, it was not until 1979 that the single-stranded RNA virus (of the Picornaviridae family) was grown in a laboratory. There is no specific treatment and the first effective vaccine was introduced in 1992.
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 occurs in less than 0.4% of people and usually manifests during the first four weeks of illness. Recovery may take 6-12 months. There is no chronic carrier state. The increasing pool of susceptible, non-immune 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
Hepatitis A vaccines are available as either monovalent, or combined with either typhoid or hepatitis B.
The four monovalent vaccines which are currently available are prepared from different strains of HAV. These are Havrix®, Vaqta®, Avaxim® and Epaxal® vaccine. These vaccines can be used interchangeably.
The ages for the monovalent vaccines are as follows:
- Havrix Monodose® is for those who are aged 16 years or older.
- Havrix Junior Monodose® is for for those who are aged 1-15 years.
- Avaxim® is for those who are aged 16 years or older.
- Vaqta Paediatric® is for those who are aged 1-17 years.
- Epaxal® is for those who are aged 1 year and older.
The hepatitis A vaccine is also available as a combined vaccination with a hepatitis B vaccine (Twinrix® and Ambirix®) and also as a combination with a typhoid vaccine (Hepatyrix® or ViATIM®).
The ages for the combined vaccines are as follows:
- Twinrix Adult® is for those who are aged 16 years or older.
- Twinrix Paediatric® is for those who are aged 1-15 years.
- Ambirix® is for those who are aged 1-15 years.
- Hepatyrix® is for those who are aged 15 years or over.
- ViATIM® for those who are aged 16 years or over.
They should be shaken before use and given into the upper arm or anterolateral thigh. For individuals with a bleeding disorder, vaccines should be given by deep subcutaneous injection to reduce the risk of bleeding. Other vaccines can be given at the same time but a different site should be used.
- The objective of the immunisation programme is to provide two doses of a hepatitis A-containing vaccine at appropriate intervals for all individuals at high risk of exposure to the virus or of complications from the disease.
- A single dose of hepatitis A vaccine has been shown to provide significant protection for up to two years.
- For travellers, the vaccine should preferably be given at least two weeks before departure; however, it can be given up to the day of departure. Although antibodies may not be detectable for 12-15 days following administration of monovalent hepatitis A vaccine, the vaccine may provide some protection before antibodies can be detected.
- The standard schedule for the combined hepatitis A and hepatitis B vaccine depends on the product:
- For Twinrix® the schedule consists of three doses, the first on the elected date, the second one month later and the third six months after the first dose.
- For Ambirix® the schedule consists of two doses, the first administered on the elected date and the second between six months and twelve months after the first dose.
- An accelerated schedule of Twinrix Adult® at 0, 7 and 21 days may be used when early protection against hepatitis B is required.
- If rapid protection against hepatitis A is required for adults (for example, following exposure or during outbreaks) then a single dose of monovalent vaccine (rather than a combined vaccine) is recommended.
- A booster dose should be given six to twelve months after the initial dose. This will give immunity beyond ten years.
- Current recommendations are for a further booster at 20 years for those at ongoing risk.
- Those who received the combined hepatitis A and B vaccine in an accelerated schedule should receive a booster dose after one year.
- It is effective to give a booster dose in those whose second dose is delayed for several years. This means that a course does not need to be re-started.
Indications for hepatitis A vaccination
Recommended for the following groups who are over 1 year of age and at risk of exposure to HAV or of complications from getting HAV:
- Travellers planning to visit moderate-risk to high-risk areas, such as the Indian subcontinent, for prolonged periods, particularly if sanitation and food hygiene are likely to be poor.
- Immunisation is no longer considered necessary for individuals travelling to or going to reside in Northern or Western Europe (including Spain, Portugal and Italy), or North America, Australia or New Zealand.
- Vaccination is also recommended for all individuals going to reside in or likely to be posted for long periods to HAV-endemic countries.
Patients with chronic liver disease
- Immunisation against hepatitis A is recommended for patients with severe liver disease of whatever cause.
- Co-infection with HAV or hepatitis B virus in patients with chronic hepatitis C virus is associated with increased morbidity and mortality.
- Therefore, the vaccine should also be considered for individuals with chronic hepatitis B or C infection and also for those with milder forms of liver disease.
Patients with haemophilia
Those with haemophilia receiving plasma-derived clotting factors should be immunised against hepatitis A (subcutaneously).
Individuals at occupational risk
- Laboratory workers who may be exposed to HAV in the course of their work.
- Staff of some large residential institutions (as transmission can occur more readily) and also staff of other institutions where standards of personal hygiene among clients or patients may be poor.
- Sewage workers who are at risk of repeated exposure to raw sewage.
- People who work with primates that are susceptible to HAV infection.
NB: most healthcare workers are not at increased risk of hepatitis A and routine immunisation is therefore not indicated. Food packagers and handlers and also staff in day-care facilities are not recommended to receive this vaccine routinely. In the event of an outbreak in these places, advice should be sought from the local Health Protection Team.
Other high-risk individuals
- Intravenous drug users (with hepatitis B vaccine or using combined vaccine).
- Men who have sex with men with multiple sexual partners.
Either passive or active immunisation, or a combination of the two, is available for the management of contacts of cases and for outbreak control.
Human normal immunoglobulin (HNIg) is preferred when protection is required in a shorter time than it takes for a protective antibody response to the vaccine. The vaccine and HNIg may be given at the same time but in different sites, when both rapid and prolonged protection are required. A single dose of monovalent hepatitis A vaccine will provide more rapid protection than the combined vaccines.
HNIg will protect against hepatitis A infection if administered within 14 days of exposure. Protection lasts for 4-6 months.
Contacts of cases of hepatitis A infection
- Hepatitis A vaccine should be given to previously unvaccinated contacts of cases of hepatitis A with onset of jaundice within the preceding week.
- Prophylaxis should be given to a wider social group of recent household visitors (kissing contacts and those who have eaten food prepared by an index case) in addition to close family.
- If a food handler is diagnosed with HAV infection, the local health protection unit (HPU) should be immediately informed to assess whether other food handlers should be considered for post-exposure prophylaxis.
- Further prophylaxis is not necessary in immunocompetent contacts who have previously received hepatitis A vaccine.
Contra-indications to hepatitis A vaccination
- Previous anaphylactic reaction to hepatitis A vaccine.
- Previous anaphylactic reaction to components of the vaccine.
- Epaxal® should not be given to those who have had a confirmed anaphylactic hypersensitivity to egg products, as a component of the vaccine is prepared on hens' eggs.
- These vaccines are not licensed for children under the age of 1 year. However, the risks of hepatitis A for children under 1 year of age are actually very low.
NB: there are very few people who cannot receive this vaccine. These vaccines may be given to pregnant women and those women who are breast-feeding.
- Local: mild, transient soreness and redness.
- General: fever, malaise, fatigue, headache, nausea and loss of appetite. However, these are not common.
Human normal immunoglobulin
HNIg is prepared from pooled plasma and can be used for more immediate passive immunisation. The use of HNIg should be limited to situations where it may have a definite advantage over vaccine. Although HNIg can provide immediate protection, antibody levels are lower than those eventually produced by hepatitis A vaccine.
Further reading and references
Hepatitis A: guidance, data and analysis; Public Health England
Manka P, Verheyen J, Gerken G, et al; Liver Failure due to Acute Viral Hepatitis (A-E). Visc Med. 2016 Apr32(2):80-5. doi: 10.1159/000444915. Epub 2016 Apr 7.
Immunisation against infectious disease - the Green Book (latest edition); Public Health England
Irving GJ, Holden J, Yang R, et al; Hepatitis A immunisation in persons not previously exposed to hepatitis A. Cochrane Database Syst Rev. 2012 Jul 117:CD009051. doi: 10.1002/14651858.CD009051.pub2.