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      Hepatitis A

      Latest update: - Authors: Ula Maniewski, Stefanie Bracke

      This viral hepatitis was previously known as ‘infectious hepatitis’ because of its infectious and epidemic nature.

      Transmission

      Hepatitis A is transmitted fecal-orally, via ingestion of contaminated food or water or via close contact with an infected individual.

      Incubation period

      The incubation period is 2 to 7 weeks, with an average of 4 weeks.

      Symptoms

      The symptoms are these of an acute viral hepatitis, including nausea, malaise, abdominal discomfort and fever followed after a few days by jaundice. Most children infected with hepatitis A remain asymptomatic or experience only mild symptoms. In contrast, adults have a higher risk (75-97%) of developing moderate to severe symptoms once infected as well as a tendency for a longer disease course. Indeed, the acute phase can take several weeks and is usually followed by a rather long post-viral asthenia of varying intensity. Occasionally, a prolonged or relapsing disease course lasting up to 6 months is observed. Despite this, a hepatitis A infection never becomes chronic.

      A fulminant disease course appears in < 0.1% of childhood hepatitis A infections. However, the incidence increases strongly with age, and it occurs in > 2% of hepatitis A infections in adults above 40 years.

      Risk areas

      Over the last decades, a substantial decrease in incidence of hepatitis A infection has been observed worldwide due to better food and water hygiene, improved sanitation, increasing socio-economic standards and (in few countries) the implementation of hepatitis A vaccine in the childhood vaccination programmes. Therefore, many countries are evolving from high and intermediate endemicity towards intermediate and low endemicity respectively.

      The WHO classifies geographical areas according to levels of endemicity based on seroprevalence rates: high (≥ 90% by age 10 years), intermediate (≥ 50% by age 15 years with < 90% by age 10 years), low (≥ 50% by age 30 years with < 50% by age 15 years), and very low (< 50% by age 30 years).

      Regions with high endemicity are sub-Saharan Africa and parts of South Asia (Afghanistan, Bangladesh, Bhutan, India, Nepal, Pakistan). Hepatitis A is typically acquired during childhood, providing immunity for nearly all adults. Considering most children experience an asymptomatic disease course, outbreaks are rather exceptional.

      Intermediate endemic areas are Latin America, North Africa, the Middle East and multiple countries in Asia. The infection is less frequently acquired during childhood, leaving more adults susceptible to hepatitis A. Hence, outbreaks are more common.

      Western Europe, Canada, USA, Australia, New Zealand and some high income countries in Asia (Japan, South Korea, Brunei, Singapore) have a low to very low endemicity. The risk of getting infected with hepatitis A virus in these areas is thus low.

      We refer to the specific country sections to have more detailed information.

      Prevention

      Products

      Monovalent vaccine with inactivated hepatitis A virus:

      For adults ≥ 18 years: Vaqta®

      For adolescents and adults ≥ 16 years: Havrix®, Avaxim®

      For children and adolescents 1 to 15 years old: Havrix junior®

      For children and adolescents 1 to 17 years old: Vaqta junior®

      Combination vaccine with inactivated hepatitis A virus and recombinant hepatitis B antigen:

      For adolescents and adults ≥ 16 years: Twinrix Adult®

      For children and adolescents 1 to 15 years: Twinrix Paediatric®

      Route of administration

      Intramuscular

      Indication

      The risk of acquiring a hepatitis A infection during a tourist trip of 1 month to a low-income country is estimated at 1 per 10,000 non-immune travellers. This is particularly true for stays in unhygienic rural settings. Hepatitis A infection is considered one of the most common vaccine preventable travel-related diseases. Accordingly, vaccination against hepatitis A is strongly advised for all susceptible individuals (unvaccinated or never infected) travelling to regions with hepatitis A endemicity, regardless of the circumstances and duration of the journey.

      Infection with hepatitis A induces lifelong immunity. Vaccination is therefore not needed for individuals with a past infection. Given the low prevalence of hepatitis A in developed countries, most travellers are susceptible. However, travellers born and raised in high endemic countries and individuals born before 1950 have a reasonable probability of being infected in childhood (often an asymptomatic infection). A thorough anamnesis with attention to former hepatitis A infections should be carried out. If in doubt, protective IgG antibodies against hepatitis A can be tested in the blood. However, if there is not sufficient time for prevaccination testing, the vaccine should be given before travel.

      For frequent travellers, immunization against hepatitis A is strongly recommended considering the widespread occurrence, the high infectivity of the virus and the strong immunogenic vaccine with favorable safety profile. A second important risk group are travellers visiting friends and relatives (VFR-travellers). Considering they account for approximately one third of travel-related hepatitis A infections, vaccination is certainly warranted for this specific group of travellers.

      Schedule

      The schedule consists of 2 injections, administered with an interval of 6 to 12 months. For most healthy travellers, a sufficient level of protection is reached after one dose. The second dose is needed to obtain long-term protection.

      In children and adolescents (see above for the age categories), a vaccine with half of the adult antigen dose is used to complete the above mentioned schedule. Although rarely indicated, infants between 6 and 12 months old can safely receive a hepatitis A vaccine. This is off-label. In that case, the first dose offers only short-term protection, and two extra doses are needed after the age of 1 year, given with an interval of 6 to 12 months.

      Persons with an immunosuppressive disorder or receiving immunosuppressive therapy need to have 2 doses of the vaccine before departure. If there is insufficient time to complete the vaccination schedule before departure, the first two doses can be administered simultaneously or with a 4 weeks interval. In that case, a third dose is needed 6 months after the 1st dose. In the immunocompromised, an assessment of the serological response after vaccination is strongly recommended.

      If the combination vaccine Twinrix® is used, at least 2 doses must be administered before departure in order to obtain sufficient protection, since this vaccine only contains half the dose of the hepatitis A antigen.

      It happens quite regularly that patients forget to take the second vaccination after 6 to 12 months. An interrupted vaccination course can be continued without restarting, even if the interval between the first and second dose encompasses several years.

      Immunity after vaccination

      The hepatitis A vaccine is very immunogenic, evoking a rapid and robust immune response. Two weeks after the first (intramuscular) injection, as much as 90% of the vaccinated individuals reach a  sufficient level of protection. After one month, this number has increased to nearly 100%. In general, there is no need to confirm the antibody level against hepatitis A after vaccination. However, in immunocompromised persons the immune response responds slower and an assessment of the antibody level after vaccination is strongly recommended.

      This excellent immune response implies that it is never too late to start the vaccination course against hepatitis A. If a person gets his first vaccine at the airport right before take-off and subsequently gets infected in the first few days of travel, sufficient antibody levels will be reached in 90% of the cases after 2 weeks, which is the minimal incubation period for hepatitis A.

      There is currently no evidence for the need of a hepatitis A booster vaccination after a full primary vaccination course (2 doses with 6 to 12 months interval) in a healthy individual.

      Immune globulines

      Since the emergence of safe and effective hepatitis A vaccines, there are only limited indications for the use of hepatitis A immune globulins. These are therefore no longer available in Belgium.

      Side effects

      The vaccine is well tolerated. We refer to the package leaflet for a detailed description of the side effects.  

      Contra-indications

      If indicated (see above), it can be safely administered to pregnant women in each trimester and during breastfeeding.

      This vaccine may be administered simultaneously with other vaccines (at 2 different injection sites or at least 2.5 cm apart if using the same injection site).

      Hepatitis A vaccines should not be administered to individuals with a known hypersensitivity to one of the components of the vaccine, nor to individuals with a hypersensitivity reaction after a previous administration of the vaccine.

      For a full description of the contra-indications and precautions, we refer to the package leaflet via the website of the FAGG or BCFI.

      References

      • Medasso, gezondheidsadviezen voor reizigers, laatste update 2016 – 2017
      • Vaccin tegen hepatitis A – BCFI
      • Maternal immunisation: Belgian guidelines (HGR 2020)
      • Vaccin hépatite A – Grossesse et allaitement (Centre de Référence sur les Agents Tératogènes 2020). 
      • Vaccination of immunocompromised or chronically ill children and/or adults (HGR 2020)
      • CDC yellow book: chapter 4: travel-related infectious diseases – hepatitis A (CDC 2019)
      • WHO position paper on hepatitis A vaccines – October 2022
      • The Global Prevalence of Hepatitis A Virus Infection and Susceptibility: A Systematic Review (WHO, 2010)
      • Balogun O, Brown A, Angelo K, Hochbert N, Barnett E, Nicolini L, Asgeirsson H, Grobush M, Leder K, Salvador F, Chen L, Odolini S, Menéndez M, Gobbi F, Connor B, Libman M and Hamer D, Acute hepatitis A in international travellers: a GeoSentinel analysis, 2008–2020, J. Travel Med. 2022 Feb.
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