Hepatitis E.

Synonyms in the broadest sense

Liver inflammation, liver parenchymal inflammation, viral hepatitis, autoimmune hepatitis, toxic hepatitis

definition

Hepatitis E is caused by the hepatitis E virus (HEV). This virus is an RNA virus, which means that it has stored its genetic information as RNA. Hepatitis E can be accompanied by a fever, rash, jaundice (Jaundice), Abdominal pain (especially in the right upper abdomen), nausea, vomiting or diarrhea. It is also possible that with a hepatitis E infection there are no symptoms at all, but the infected person is still contagious to others.

The virus occurs worldwide. In Germany, genotype 3 of the HEV is mainly present. Domestic pigs and wild boars are seen as a so-called reservoir for the virus, whereby the virus can be transmitted through food that is not completely cooked through. The number of annual infections with hepatitis E is also increasing again.

Symptoms of hepatitis E infection

After infection, it takes 15-64 days for the disease to break out (incubation period). The symptoms of hepatitis E do not differ from hepatitis A.
The majority of childhood infections cause no symptoms at all, although HEV infections rarely occur in patients under 20 years of age.
In the so-called prodromal stage, which lasts 2-7 days, flu-like symptoms such as:

• high temperature
  and
• Fatigue,
  also kick
• Nausea,
• Loss of appetite,
• Tension pain in the right upper abdomen
  and
• possibly diarrhea.
  Further symptoms are more acute
• skin rash
  and
• Joint pain, but this does not always occur.

Read more on this topic: Symptoms of hepatitis E.

in the second stage (Duration 4-8 weeks) the virus settles in the liver. In adults there is now one Jaundice (Jaundice). In addition to the discoloration of the white dermis in the eye, and then the entire surface of the body, this liver manifestation manifests itself in a Darkening of urine with simultaneous Discoloration of the chair. The liver is now significantly enlarged and painful. In approx. 10-20% of the cases can also be a Enlargement of the spleen and Swelling of the lymph nodes determine.

At 3% of HEV infected people (up to 20% of pregnant women) develop a so-called fulminant hepatitis E. with three classic symptoms (triad). Jaundice (Jaundice), Coagulation disorder and Disorder of consciousness. Here, the liver damage is so massive that the liver is no longer able to form coagulation factors and break down the blood pigment, which from a certain concentration is then deposited in the skin and discolored it yellow. In the case of fulminant hepatitis E, therefore, it comes to a complete one Liver failure.

In contrast to the other forms of hepatitis, hepatitis E has so far no chronic courses described. The chronic hepatitis is defined as inflammation of the liver that has not healed after six months. Possible consequences of chronic hepatitis are connective tissue remodeling of the liver (Cirrhosis of the liver) and a so-called hepatocellular carcinoma (HCC), i.e. Liver cancer.

What is the typical course of a hepatitis E infection?

In Germany, the disease with the hepatitis E virus often has few or no symptoms. If symptoms occur, these are usually mild and spontaneous healing occurs. Symptoms may affect the gastrointestinal tract and cause discoloration of stools, dark urine, nausea, vomiting, and diarrhea. In contrast to the other inflammations of the liver, jaundice rarely occurs (Jaundice). In rare cases, however, a severe infection with severe symptoms and pronounced liver inflammation can also occur. This is especially the case if the person already has liver disease.

In addition to the typical symptoms of hepatitis, neurological involvement such as meningitis can also occur. Although hepatitis E heals in most cases, it can also become chronic (persistent) in people with weakened immune systems and, in rare cases, lead to liver failure. But even with a weakened immune system, there are often no symptoms.

Duration of illness

The course of symptomatic hepatitis E can be divided into different stages: The prodromal stage with symptoms such as fever, fatigue and tenderness in the right upper abdomen lasts up to a week. The following second stage with jaundice lasts up to eight weeks. Usually, however, the liver values ​​improve after just 14 days. In rare cases, the course can be severe and, in the case of immunocompromised, lead to permanent infection. Hepatitis E should be avoided, especially in pregnant women, as the risk of severe disease is increased and mortality during pregnancy is also more likely.

Diagnosis

The diagnosis of hepatitis E is based on a medical, clinical examination as well as a Antibody detection (Anti-HEV IgM and Anti-HEV IgG) in the blood. Virus detection in stool or in the liquid part of the blood (serum) is based on the direct evidence of the Hepatitis E RNA (Ribonucleic acid), i.e. part of the human genome, through a so-called "Polymerase chain reaction' (PCR) possible. Here, certain sections (sequences) of the DNA are reproduced in a enzyme-dependent manner and thus enable detection of a hepatitis E infection.

If there is an isolated increase in anti-HEV IgM without an increase in anti-HEV IgG values, the presence of HEV RNA is evidence of an acute hepatitis E infection. An increase in the anti-HEV-IgG value (without an increase in anti-HEV-IgM) speaks for an infection that has already passed; with the anti-HEV-IgG value, a hepatitis E infection can be detected even years after an infection.

What tests for hepatitis E are there?

If symptoms and elevated liver enzymes suggest hepatitis E, this must be proven by means of anti-HEV IgM detection. Normally, these antibodies can already be measured when early symptoms appear and can remain detectable for three to six months. If there are no symptoms, but hepatitis E is suspected, the pathogen should be detected directly from the blood or stool, e.g. done by means of PCR. The detection of HEV-RNA from a stool or blood sample is proof of a fresh HEV infection.

The later anti-HEV-IgG antibodies can often be tested positive even when the symptoms begin, but can also remain positive if the infection has ended and has healed. In immunosuppressed people, specific antibodies are usually only detectable in the blood later. A nucleic acid amplification technique (NAT) such as PCR should therefore always be used in order to enable direct virus detection. The risk of persistent hepatitis E infection is increased in immunosuppressed people.

Change in liver values

On the one hand, liver involvement leads to a significant increase in the so-called transaminases, which can indicate liver cell destruction when increased in the serum. The transferases ALT (alanine aminotransferase) and AST (aspartate aminotransferase) are measured, whereby the quotient of AST and ALT can provide information about the severity of liver cell destruction (De-Ritis quotient). In severe cases, this quotient is over 1.In the case of liver damage, the synthesis of albumin and coagulation factors, for example, can also be reduced and predict acute liver failure.

Read more on the subject at: Increased liver values

Virus and transmission

Hepatitis E is an inflammation of the liver caused by the hepatitis E virus (HEV for short) (hepatitis). HEV is a so-called RNA virus that belongs to the calicivirus family. The genome of the virus is encoded on the RNA. There are 4 different RNA versions (genotypes) of the hepatitis E virus.

As a rule, one becomes infected with the HEV faecal-oral. Faecal-oral means that a carrier of the virus excretes it (faecal) and the virus is now ingested by the newly infected person via the mouth (orally). This happens, for example, as a smear infection in the event of poor hygiene, but also via contaminated drinking water or contaminated food. Since a droplet infection cannot take place from person to person, it is sufficient to carefully boil the tap water in holiday destinations before consumption.
Transmission via blood and body fluids has been observed in rare cases (parenteral transmission). However, this only works in the so-called viremic phase, when the virus is in the blood of an infected person. Animals such as sheep, pigs, monkeys, rats and mice are sometimes considered to be a natural reservoir for this pathogen.

In Asia, Central and North Africa, the Middle East and Mexico, there are some epidemics of hepatitis E, i.e. many new cases that spread in a defined area at the same time. Monsoon times in particular are predestined for such epidemics due to their spread over water.
In Germany the HEV only occurs in isolated cases. While only 51 cases were reported in 2006, half of which were brought in from abroad, in 2009 there were around 100 cases that arose from native virus strains.

After ingestion of the virus, it invades the cells of the body. Here, the virus docks onto the cell with adhesive spikes, similar to small feet, and injects its genetic material into the host cell. The host cell incorporates the foreign DNA (in this case RNA) into its metabolism and now produces the virus proteins. Once the virus parts have been formed within the cell, the newly created virus is put together and leaves the foreign cell, which is destroyed in the process. Viruses do not have their own metabolism and are therefore dependent on infiltrating foreign organisms in order to continue to multiply.

infection

The hepatitis E virus is infected by the faecal-oral route. This means that pathogens with the stool (fecal) excreted, later via the mouth (orally). This transmission from person to person is rather rare, although it is quite possible that an acutely ill person infects other people directly in this way.
Infection occurs much more often indirectly through contaminated water or insufficiently cooked or cooked meat products. A type of hepatitis E virus that occurs in this country (Genotype 3) can be transmitted via wild boar, pigs and deer. The best way to protect yourself against hepatitis E infection is to heat meat products to over 70 ° C. Contact with infected animals should also be avoided.

In addition to pigs, wild boars and deer, monkeys, sheep, mice and rats are also the pathogen reservoirs.

Especially when the hygienic standards are poor, e.g. Hepatitis E is often infected in third world countries, during environmental disasters (e.g. floods or in the monsoons), in war zones or in refugee shelters. In these cases, contaminated drinking water is the main source of transmission. To protect against infection through contaminated drinking water, water should only be consumed from water bottles sealed by the manufacturer.

Also an infection by one Liver transplant (If the donor has hepatitis E disease) is possible.

In very rare cases, infection with hepatitis E can also occur through contaminated blood products and blood transfusions, although this transmission value is rather atypical.

Contagion through coughing, sneezing, kissing etc. (Droplet infection) and sexual intercourse is unknown.

Most of the hepatitis E infections that occur in the western world are recorded as travel sicknesses, which mainly affect the sick people. of trips to the above Bring risk areas.

How contagious is hepatitis E?

How contagious hepatitis E is is not yet fully understood. The duration of infection is between one week before and four weeks after the first symptoms appear. The virus is excreted in the stool. The hepatitis E virus can then be transmitted by smear infection if the hygiene is inadequate. If the virus becomes permanently infected, it must be assumed that the virus can also be transmitted to other people and the environment during this time. Fecal-oral transmission from human to human is rare, however.

Is it possible to get infected from person to person?

In Germany, the hepatitis E virus is mainly transmitted through undercooked foods such as wild boar or domestic pigs. The HEV genotype 3, which occurs mainly in Germany, is only very, very rarely transmitted from person to person via smear infection. The virus has a fecal-oral effect (i.e. pathogens excreted in the stool are absorbed through the mouth). Hepatitis E viruses (HEV-1 and -2) acquired while traveling are more likely to be transmitted through human contact. These are countries with a low standard of hygiene, whereby people with hepatitis E can also be infected through contaminated water or other food. This also includes seafood such as mussels.

Therapy and prophylaxis

After the diagnosis has been made by talking to the patient (anamnesis), physical examination and evaluation of the blood count (antibodies of the IgM and IgG type against HEV can be detected in the blood serum), symptomatic therapy begins.
Since acute hepatitis E takes time to heal, only the symptoms can be combated and general measures can be taken to protect the liver. This includes, for example, avoiding alcohol and liver-damaging medication, if possible. Physical rest (bed rest) is essential. For nausea, diarrhea and pain, liver-friendly medication is given.

98% of all acute HEV infections heal completely. Only about 2-3% take the brilliant course described above. In pregnant women it is 20%.
A hepatitis E vaccine has now been successfully tested. Vaccination is an active immunization, which means that the body is stimulated to produce antibodies against the virus. Three vaccinations after zero, one and six months are required for approx. 90% protection. Since infections only occur very rarely in our latitudes, vaccination is not mandatory. There is currently no passive immunization for hepatitis E. In passive immunization, the patient is injected directly with effective antibodies against the HEV after a possible infection. Although these are broken down again by the body, they bridge the time that the organism needs to produce antibodies itself as part of an active immunization.
Adequate food and drinking water hygiene is required when traveling to HEV-prone countries. Water from the tap must be boiled for a sufficiently long time. Since pigs and sheep can be natural reservoirs for HEV, their meat should not be consumed raw in endangered regions. It is also advisable to carry out hygienic hand disinfection after contact with infected people as a preventive measure.

vaccination

There is currently no approved vaccine against hepatitis E in Germany, but a vaccine against hepatitis E has been approved in China since 2012.
However, this vaccine is probably only effective against the hepatitis E viruses there (Genotype 1) and not against the European hepatitis E virus types (Genotype 3). Since the vaccine has already shown success in China, there will certainly be a vaccination against the hepatitis E viruses common in this country in the next few years, if there are sufficient studies.
Until then, the only prevention (prophylaxis) against infection with hepatitis E is to cook meat products and offal (especially from pigs and wild animals) at temperatures of at least 70 ° C. Uncooked fruit and vegetables should also only be eaten cooked or peeled in areas with a higher risk of infection with hepatitis E, and water should only be drunk from sealed bottles.

Complication in pregnancy

Infections with hepatitis E are more frequently associated with complications and severe courses in pregnancy than in non-pregnant women. An infection during pregnancy can be life-threatening for the pregnant woman, especially in the last trimester of pregnancy there is an increased mortality rate of up to 20%. Also the likelihood of an acute one Liver failure is increased during pregnancy. However, the prediction (prognosis) in pregnant women with acute liver failure is no worse than in non-pregnant women.

As with non-pregnant people, however, pregnant women can also experience uncomplicated, typical symptoms such as nausea, fever and Jaundice (Jaundice) or a completely symptom-free course of the disease.

Due to the more often complicated processes, pregnant women should pay more attention to good hygiene measures, avoid traveling to risk areas (Southeast Asia, Central Asia, the Middle East, South America, especially Mexico, Africa) and consume meat only sufficiently cooked.

incubation period

The time between infection with the hepatitis E virus and the onset of the first symptoms of the disease (nausea, Vomit, flu-like symptoms, fever, Yellowing of the skin and eyes (Jaundice), dark urine, discolored stool) is on average between 30 and 40 days. Earlier appearance of the initial symptoms and a longer incubation period are quite possible.

Does hepatitis E have to be reported?

According to the Infection Protection Act (IfSG), hepatitis E must be reported even if it is suspected. Thus, of course, the confirmed hepatitis E infection (direct or indirect evidence) and death from the disease must be reported by name to the health department. The report must be submitted to the health department no later than 24 hours after the suspicion or discovery.