Hepatitis E primary prevention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Hepatitis E is a zoonosis that may be prevented by avoiding contact with the virus, and by immunization through vaccination. In order to avoid infection, measures such as appropriate sanitation, hygiene, and maintenance of the quality of the public water supplies should be observed. Also, thorough cooking of pork meat and avoidance of shellfish in endemic regions should be pursued. Blood transfusions represent a rare form of transmission that may be minimized by screening blood donations. Two vaccines have been developed so far, and one of them has been approved in China. However, no further studies have been conducted regarding the distribution of the vaccine worldwide.

Prevention

Hepatitis E may be prevented by two ways:[1]

Hepatitis E is a zoonosis, therefore prevention of the disease should start by avoiding transmission of the virus from animals to humans. As almost every HEV infection is spread by the faecal - oral route, improving sanitation is the most important measure, along with good personal hygiene. High quality standards for public water supplies and proper disposal of sanitary waste have resulted in a low prevalence of HEV infections in many well developed societies.[2]

For travellers to high endemic areas, the usual elementary food hygiene precautions are recommended. These include:[3]

  • Avoiding drinking water and/or ice of unknown purity
  • Eating uncooked shellfish, uncooked fruits or vegetables that are not peeled or prepared by the traveller
  • Cook pork thoroughly
  • Avoid eating shellfish

Although rare, transmission has been reported through blood transfusions. Because infection is often asymptomatic, and most blood products are not tested for the presence of the virus, transmission of hepatitis E may occur unnoticed. This represents a concern for immunosuppressed patients, and for those with chronic liver disease, who are at risk of developing chronic hepatitis E. Hence, screening of blood products is considered a preventive measure.[1][4]

Guidelines for Epidemic Measures

The following measures should be observed in an epidemic situation:[3]

  • Determination of the mode of transmission
  • Identification of the population with an increased risk of infection
  • Elimination of a common source of infection
  • Improvement of sanitary and hygienic practices to eliminate fecal contamination of food and water

Vaccination

Patients who have recovered from HEV infection show immunity against HEV, which seems to offer life-long protection against the development of symptomatic hepatitis E.[5] Vaccination can also induce protective immunity. So far 2 vaccines have been developed:[6][1]

  • The first vaccine showed 96% efficacy in Nepalese soldiers, after administration of 3 doses. It is expressed by insect cells. Unfortunately, no further developments were made to the vaccine.[7]
  • A second vaccine has been developed and approved in China, with 94-100% efficacy in preventing acute hepatitis E. The vaccine is produced by bacterial cells (E. coli), does not show relevant side-effects, and is safe for administration in pregnant women. Further studies are required in high-risk groups, such as immunocompromised and end-stage liver disease patients.[8]

Risk for travellers

Travellers to developing countries may be at risk when exposed to poor conditions of sanitation and drinking-water control.

Vaccine

  • A vaccine against HEV has recently been developed and licensed in China. The vaccine contains a recombinant viral capsid protein corresponding to genotype 1 of HEV, but is likely to protect against all four genotypes. Three doses of the vaccine are given intramuscularly at 0, 1 and 6 months. So far, this vaccine has shown a favourable safety profile as well as excellent immunogenicity and clinical efficacy when used in healthy individuals aged 16-65 years.
  • The duration of protection is at least two years. Because of a lack of sufficient information on safety, immunogenicity and efficacy in important target groups such as children under 16 years of age, pregnant women and people with chronic hepatic disorders, WHO does not currently recommend this vaccine for routine use in national programmes of endemic countries. However, vaccination against HEV may be considered in special situations where the risk of contracting HEV is particularly high. For example, WHO recognizes the high risk of HEV infection for travellers, health-care and humanitarian relief workers deployed or travelling to areas where there is an ongoing outbreak of hepatitis E. In such circumstances, each person should be evaluated individually for risks and benefits of vaccination against HEV.

Precautions

Travellers should follow the general recommendations for avoiding potentially contaminated food and drinking-water.

Summary of vaccine data

Considerations for travellers for Hepatitis E vaccination
Type of vaccine
  • Recombinant vaccine based on genotype 1 capsid protein which cross-protects against all 4 genotypes of hepatitis E virus of human relevance.
Number of doses
  • 3 (administered intramuscularly at 0, 1 and 6 months). The possible need for booster doses after >2 years is not yet defined.
Contraindications
  • Not described, except for serious allergy to vaccine components. Sensitivity to previous dose.
Adverse reactions
  • Rare local reactions.
Before departure
  • 4 weeks.
Indication
  • Travellers, health-care and humanitarian relief workers travelling to areas during outbreaks of hepatitis E.
Special precautions
  • So far, no safety data are available on its use in children, the elderly, pregnant women, or patients with chronic liver disease or immunodeficiencies.

References

  1. 1.0 1.1 1.2 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
  2. Mandell, Gerald (2010). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Churchill Livingstone/Elsevier. ISBN 0443068399.
  3. 3.0 3.1 "Hepatitis E".
  4. Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
  5. Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ; et al. (2010). "Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial". Lancet. 376 (9744): 895–902. doi:10.1016/S0140-6736(10)61030-6. PMID 20728932.
  6. Wedemeyer H, Pischke S, Manns MP (2012). "Pathogenesis and treatment of hepatitis e virus infection". Gastroenterology. 142 (6): 1388–1397.e1. doi:10.1053/j.gastro.2012.02.014. PMID 22537448.
  7. Shrestha MP, Scott RM, Joshi DM, Mammen MP, Thapa GB, Thapa N; et al. (2007). "Safety and efficacy of a recombinant hepatitis E vaccine". N Engl J Med. 356 (9): 895–903. doi:10.1056/NEJMoa061847. PMID 17329696.
  8. Wedemeyer H, Pischke S (2011). "Hepatitis: Hepatitis E vaccination--is HEV 239 the breakthrough?". Nat Rev Gastroenterol Hepatol. 8 (1): 8–10. doi:10.1038/nrgastro.2010.207. PMID 21212772.

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