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The pathogen is transmitted via raw meat and contaminated water. The disease is usually asymptomatic.

Hepatitis E is a viral inflammation of the liver. It is caused by the hepatitis E virus, HEV for short. It occurs primarily in Asia and India. In Germany, it is often travel-related.

Epidemiology

Hepatitis E infections are primarily spread in Asia and Africa, but are present worldwide. The HEV virus genotypes, epidemiology and clinical manifestations vary between different regions. While genotypes 1 and 2 have so far only been detected in humans, types 3 and 4 also occur in animals such as domestic pigs and reindeer. In Europe and North America, genotype 3 of hepatitis E is particularly widespread.

It is estimated that around 20 million people worldwide are infected with HEV every year, 3.3 million of whom develop symptomatic hepatitis E. The disease mainly occurs in adulthood, with a plateau between the ages of 40 and 75. Men between the ages of 60 and 69 are particularly frequently affected.

Causes

Hepatitis E is caused by the hepatitis E virus (HEV), a single-stranded RNA virus from the hepevirus family (Hepeviridae). In humans, the four genotypes 1-4 and several subgenotypes are distinguished. Pigs are the main reservoir of HEV, particularly in Switzerland and other industrialized countries, and transmission from animals to humans is common.

Pathogenesis

Hepatitis E virus (HEV) is transmitted either fecal-orally or zoonotically, i.e. it can pass from animals to humans. Fecal-oral transmission usually occurs through contaminated drinking water or food. In Asia and Africa, this is the most common route of infection for genotypes 1 and 2 of HEV.

In industrialized countries, HEV is mainly transmitted through the consumption of raw or undercooked pork, game meat or through the consumption of filtering aquatic organisms. Human-to-human transmission is not known for genotypes 3 and 4. However, HEV1 and HEV2 infections can also be transmitted from person to person through smear infections, for example within families or households. Transmission can also occur via blood, blood products, contaminated medical equipment or transplanted organs with a high viral load, even if this route of infection is rare in Germany due to high safety standards. The duration of the risk of infection of infected persons cannot be precisely determined on the basis of current studies. The virus could be detected in the stool of HEV-infected persons approximately one week before to four weeks after the onset of the first symptoms. In the case of a chronic infection, those affected are probably active excretors and contagious until the virus has been eliminated.

After an HEV infection, it takes between 15 and 64 days for the first symptoms to appear.

The exact pathophysiology of hepatitis E is still unknown. It is assumed that the virus could multiply in the gastrointestinal tract and enter the liver via lymph nodes and blood vessels. There it multiplies in the cytoplasm of the liver cells and from there it can re-enter the bloodstream and bile. As bile is released from the liver into the digestive tract, the virus could return to the intestines and excretions in this way. However, whether this theory is correct cannot be scientifically confirmed at present.

As with other viral hepatitis, the liver-damaging effect of HEV is probably not triggered directly by the virus itself, but as a result of the immune response. Cytotoxic T cells and natural killer cells (NK cells) attack the infected cells and destroy them. It is assumed that this leads to the destruction of liver cells and the development of hepatitis symptoms.

Symptoms

Most hepatitis E (HEV) infections are asymptomatic and self-limiting. The typical symptoms include those of classic hepatitis, including

  • Fever
  • Tiredness and fatigue
  • Loss of appetite or even anorexia
  • nausea and vomiting
  • Upper abdominal pain
  • Itching and rashes
  • Joint pain
  • Jaundice (icterus) with dark urine and light-colored stools
  • A slightly enlarged liver (hepatomegaly)

The symptoms usually last between one and six weeks and cannot be distinguished from other viral hepatitis.

In rare cases, hepatitis E can take a fulminant course and lead to liver failure, especially if pregnant women are affected. Around 20 to 25% of HEV infections are fatal if they occur in the third trimester of pregnancy. Genotype 1 infections in particular carry a high risk.

A further risk of HEV infection is extrahepatic manifestations, which include clinical pictures that bear no symptomatic resemblance to viral hepatitis. These include, for example, Guillain-Barré syndrome, neuralgic amyotrophies, encephalitis, meningoencephalitis and myositis.

In the majority of cases, hepatitis E does not lead to chronicity. Exceptions are immunosuppressed patients, in whom HEV infections can usually be asymptomatic. Nevertheless, like all chronic hepatitis, there is a risk that it can lead to liver cirrhosis.

Diagnostics

The clinical picture of hepatitis E is similar to that of many viral hepatitis. Only a travel history can provide information if necessary. Laboratory diagnostics are therefore of great importance in hepatitis.

Laboratory: The blood test shows significantly elevated transaminases (GOT and GPT) and possibly also an increase in alkaline phosphatase (AP) and gamma-GT. In the case of jaundice, there is also a significantly elevated total bilirubin in the serum and a significantly elevated urobilinogen in the urine.

As similar constellations can also occur with other viral hepatitis, various medications such as paracetamol, fungal toxins, alcohol, storage diseases, alpha-1-antitrypsin deficiency and autoimmune hepatitis, serology is required to confirm the diagnosis of hepatitis E.

In fresh HEV infection or acute hepatitis, the markers anti-HEV-IgM and HEV-RNA are elevated in the blood and stool. Antibodies may already be detectable by ELISA when the first symptoms appear. Due to possible uncertainties in IgM reactions, a positive anti-HEV IgM marker requires an additional confirmatory test that detects HEV RNA using nucleic acid amplification techniques such as PCR. At this point, anti-HEV IgG antibodies may already be detectable in the serum. However, if only anti-HEV-IgG antibodies are detectable and the other two markers are negative, this indicates an earlier infection.

In immunocompromised patients, antibody tests can be falsely negative. For this reason, the pathogen is detected directly in this specific patient group using nucleic acid amplification technology.

Therapy

Most hepatitis E infections are asymptomatic or heal on their own. Drug therapy is not normally necessary if the course is self-limiting. However, those affected should take it easy, stay in bed, drink plenty of fluids and avoid alcohol and liver-toxic medication. Symptoms can be treated symptomatically.

In around 3% of cases, however, hepatitis E takes a severe course. In such cases, antiviral therapy with ribavirin and PEG-interferon-alpha can be considered. The therapy is carried out according to valid protocols. If these measures fail, liver transplantation remains the last option.

Chronic hepatitis E infections also require therapy to eliminate the virus and prevent liver damage that can lead to cirrhosis.

Prognosis of hepatitis E:

What to expect for those affectedIn most cases, hepatitis E heals completely, with a lethality rate of less than 1%. However, pregnant women, especially in the third trimester with genotype 1, have a higher risk of a severe course (lethality of 20-25%). The prognosis is also less favorable with organ transplants and immunosuppression, with a higher probability of chronic courses.

Prophylaxis and prevention of hepatitis E: tips for protection against infection

No vaccination against hepatitis E is available in Germany. The following hygiene measures are important when traveling to regions with genotypes 1 and 2:

  • Boil tap water
  • Use boiled water for ice and chilled drinks
  • Avoid raw or undercooked food (principle: "Peel it, cook it, or forget it!")
  • Pregnant women should avoid endemic areas.

In Switzerland, animal products from pigs and game should be cooked thoroughly (at least 71°C for 20 minutes) and kitchen hygiene should be observed to prevent cross-contamination.