Hepatitis E

Hepatitis E

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV). HEV occurs sporadically in developed countries, primarily in the genotypes 3 and 4, which originate in animals. Infection with HEV often progresses in general without symptoms. The infection can also lead to an acute liver infection that often causes more serious complications, especially in pregnant women.

Annually 20 million Infections in Humans

According to the WHO, 20 million HEV infections, more than 3 million acute cases, and approximately 70,000 deaths are linked annually to Hepatitis E. These figures are mainly determined by outbreaks in developing countries. Hepatitis E is transmitted in these countries primarily via drinking water contaminated with excreta. In these countries, the genotypes 1 or 2 of the virus are involved, and these variants occur only in humans.

Where does Hepatitis E occur?

  • Hepatitis E in humans occurs more often in developing countries (genotypes 1 and 2), presumably as a result of contaminated drinking water and conditions of poor hygiene.
  • In industrialised countries, the disease is less prevalent in humans. In the Netherlands and the rest of Europe as well, 5 to 10 per cent of the population has antibodies against HEV. On this basis, it may be deduced that they too have come into contact at some point with this virus.

How do Europeans become infected?

Infection with the HEV genotype 3, the most prevalent type in the Netherlands and the rest of Europe, may result from eating infected meat or drinking contaminated water. Tracing the cause of the infection is often difficult, as the incubation period can take up to 60 days and on occasion longer. The virus can also be transmitted via blood transfusion and organ transplants. Hepatitis E virus genotype 3 has been found, apart from in humans, in domestic pigs, wild boar, certain deer species and shellfish.

Hepatitis E in the Netherlands

The number of cases resulting from HEV in the Netherlands is estimated at 1 to 5 infections per 100,000 people per year. Pigs are probably the most important source of these infections. On the basis of various studies, it has been found that HEV occurs on more than 50% of the pig fattening farms in the Netherlands. There are no indications that this is changing. Hereditary material from the virus has been shown in pig liver sold in butchers. In France, the "living virus" has been found in sausage made from raw pig liver.

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Hepatitis E as Pathogen

Four types of the Hepatitis E virus occur in humans and other mammals. Genotype 1 and genotype 2 occur in humans exclusively in the tropical regions of Africa and Asia. Genotype 3 and genotype 4 occur in both humans and animals and can be transmitted from animals to humans (zoonotic). In Europe we see genotype 3 viruses virtually exclusively, and very sporadically genotype 4. Hepatitis E virus genotype 3 occurs in the Netherlands in domestic pigs and in wild fauna, primarily wild boar and deer.

Hepatitis E Pathology

In humans, the progression of a hepatitis E virus infection is usually without symptoms. In a small number of humans, HEV may however lead to acute liver inflammation with fever and nausea. In the case of pregnant women, the progression of the disease may be more severe and may cause complications more often. Direct natural infection from patients to others is rare.

Distribution/Transmission of Hepatitis E

Pigs, wild boar, certain deer species, shellfish and humans can become infected with HEV genotype 3. The virus is excreted via faeces and urine; if these end up in (sources for) drinking water, animals and humans drinking this water can also be infected with the virus. Which route is the most important is not yet clear. Wageningen Bioveterinary Research is conducting research into the transmission routes. The liver is the most important target organ for the virus, although high concentrations can also occur in other organs and in the blood. This means that blood transfusion and organ transplants are also possible transmission routes in humans. Proper heating of infected material kills the virus. Contaminated food eaten raw, for example oysters, forms a potential infection route.

Research into the hepatitis E virus is important in order to find out whether incidence, and so the risk to humans, is rising. In addition, it is important to find out whether virulent variants arise and to gain a better understanding of the (most important) transmission routes.

Options for Treatment

The hepatitis E virus can cause liver inflammation in pigs, although evident symptoms resulting from the hepatitis E virus are in fact never found in pigs. For this reason, pigs are in fact never treated for hepatitis E. There is also no vaccine available for preventive treatment. Humans that develop serious hepatitis following infection with HEV can be treated with antiviral medication, but this is not always successful and requires long-term treatment with hospitalisation.

Prevention and Control of Hepatitis E

The hepatitis E virus can also cause a liver infection in mammals, but this is not associated with evident symptoms. The disease is not notifiable. No preventive measures for pigs are taken for this reason. Humans are advised not to drink contaminated water or consume products that have been in contact with the virus. Consumption of inadequately cooked pork (especially liver) or game (especially wild boar or deer) is advised against.

Diagnosis

The hepatitis E virus (HEV) is very difficult to culture. The PCR test is almost always used to show the presence of HEV. The virus (RNA) can readily be shown with the aid of PCR in blood and (liver) tissue samples. Standard procedures have also been developed for the detection of the hepatitis E virus in food and water samples.

For determining antibodies against the hepatitis E virus, various immunoassays, especially ELISAs, are used. Over recent years, these tests have improved radically, but there are still considerable differences in quality. While 4 genotypes of HEV occur in mammals (including humans), we can only one distinguish a single serotype. That is to say that the antibody tests are unable to distinguish between antibodies generated by one of these 4 types. Both the PCR and the antibody tests can be routinely conducted by Wageningen Bioveterinary Research in all the abovementioned samples.