A human liver between two palms of a woman on blue and green background. The concept of a healthy liver.

Hepatitis E: causes, symptoms, diagnosis, treatment and transmission

By Cristiano Antonino On May 8, 2023

Hepatitis E is a liver disease caused by HEV that, similar to the aetiological agent of hepatitis A, is mainly transmitted via the faeco-oral route, i.e. through the consumption of water and food contaminated with infected faeces

The hepatitis E virus (HEV) is a capsid-free RNA virus of the family Hepeviridae

To date, four genotypes (1-4) pathogenic to humans of hepatitis E have been identified.

Genotypes 1 and 2 are pathogenic to humans only, whereas genotypes 3 and 4 are detectable in both humans and animals.

Hepatitis E is quite rare in Italy, as it is in other industrialised countries

Instead, it is often present in epidemic or sporadic form in developing areas, where overcrowding and poor hygiene conditions facilitate its spread.

The infection is present in many areas of the world with a greater number of new cases (incidence) in the countries of South East Asia and Latin America.

In Italy, there are relatively few cases reported to the SEIEVA surveillance system of the Istituto Superiore di Sanità (Italian National Institute of Health) (just under 200 in the period 2007-2016), but there is still a lack of knowledge of how the infection is transmitted and of the signs of its presence.

HEV infections generally proceed asymptomatically or present with mild, non-specific symptoms including fatigue, lack of appetite, nausea, vomiting, headache, muscle and joint pain.

If liver inflammation does occur, it is often a self-limiting form that resolves spontaneously without complications.

In some rare cases, hepatitis E may develop fulminantly with acute liver failure.

Pregnant women who have suffered a severe course of the disease are particularly at risk.

Epidemiology of hepatitis E

Hepatitis E is an infectious disease that is widespread throughout the globe.

It is estimated that 1/3 of the world’s population has been exposed to the virus.

It is also estimated that 20 million people become infected with the hepatitis E virus (Hepatitis E) every year, that more than 3 million experience symptoms, and that at least 600,000 HEV-associated deaths occur annually.

The age group most affected by hepatitis E is between 15 and 40 years.

The global distribution of HEV has different epidemiological trends and is evidently related to socio-economic and ecological factors.

In developing countries, hepatitis E occurs in the form of large epidemics spread through the consumption of contaminated water or person-to-person contacts.

In developed countries, on the other hand, where hepatitis E was traditionally considered a travel-associated disease in the past, there has been an increasing number of indigenous cases reported in Europe in recent years.

HEV is currently endemic in the EU, with HEV genotypes known to infect humans (HEV1-4 and HEV7) and animals (HEV3-6).

EU countries mainly report autochthonous HEV3 infections associated with the consumption of meat (especially pork, undercooked or insufficiently cured).

According to the SEIEVA observatory – the Integrated Epidemiological System of Acute Viral Hepatitis coordinated by the Istituto Superiore di Sanità (ISS) – 12 cases of hepatitis E were detected in the first half of 2021 (together with 39 cases of hepatitis A, 34 cases of hepatitis B, 13 cases of hepatitis C).

In addition, the bulletin confirms what has already been observed in recent months, namely that the number of reported cases of viral hepatitis.

Indistinctly for all types, there has been a clear decrease since February 2020 compared to previous years.

The reported decrease tends to be attributed to COVID containment measures.

A decrease in notifications can also be attributed to increased activity within infectious disease departments and prevention departments.

Symptoms

Viral hepatitis E is, in most cases, self-limiting and symptoms regress within a few weeks.

Only in some rare cases does the infection cause severe liver damage.

The infection presents itself with the appearance of complaints very similar to those of hepatitis A.

After an asymptomatic incubation period of 2-9 weeks, abdominal pain, fatigue, nausea, vomiting, fever and general malaise may occur.

Subsequently, jaundice appears.

How it manifests itself

Other typical but not exclusive symptoms of HEV infection are:

anorexia, understood here as decreased appetite or lack of appetite. It is manifested by a lack of the normal feeling of hunger when in need of food. Many diseases can manifest with anorexia. In addition to hepatitis, these include oesophagitis, gastritis, peptic ulcer, gastric carcinoma, appendicitis and Crohn’s disease.
increase in transaminases, a class of enzymes responsible for transferring the amino group (-NH2) from one amino acid to another molecule that lacks it (called an α-keto acid). This ‘exchange’ of amino groups is essential for metabolism, as it enables excess amino acids to be disposed of by mutating them into molecules that can easily be used for energy or into other amino acids that the body needs. The most important transaminases are alanine aminotransferase (ALT or GPT) and aspartate aminotransferase (GOT or AST). Transaminases are present in various tissues, but are mainly located in the liver and, to a lesser extent, in the heart, muscles and skeleton. Therefore, any cause causing damage to these tissues also generates the release of transaminases into the blood, with an increase in their plasma concentration.
Extremely high blood transaminase values (more than 10 times the normal value) may indicate acute necrosis of liver cells, damage due to acute viral or drug-induced hepatitis (or toxins), rejection in the case of transplantation, metabolic hepatopathies, ischaemic damage or a liver attack. Modest increases (value between 5 and 10 times the normal range) are found in chronic viral hepatitis, alcoholic hepatitis, hepatic steatosis, Wilson’s disease and biliary obstruction. Slight increases (value above 1 but below 5 times normal) occur in cases of liver cirrhosis, non-alcoholic steatosis (fatty liver) and cholestatic disorders. There are also extra-hepatic causes of increased transaminases that are not detected here.
chills
muscle pain
headaches.

If contracted during pregnancy, hepatitis E has a particularly serious course and can develop into the fulminant form (approx. 10-20% of cases).

Transmission of hepatitis E

As mentioned above, the most common route of infection is oro-fecal transmission through consumption of contaminated water or food (in endemic areas with poor hygiene conditions).

Indeed, the hepatitis E virus (HEV), originating from the faeces of infected people or animals, can survive in an active form and contaminate water used for food or agriculture.

Furthermore, the virus is present in the meat of animals (pigs, wild boar) that have not been treated or not properly cooked.

Hepatitis E is mainly transmitted by ingesting water, fruit and vegetables contaminated with faecal material from infected persons.

It is mainly spread in overpopulated areas where there is inadequate sewage management.

The preparation of meals by HEV-infected persons may spread the infection within the household or community.

To a much less significant extent, transmission of the infection may occur

zoonotic, i.e. due to consumption of inadequately cooked pork
maternal-fetal, although this has only been detected in a small number of cases.

Contagion and symptoms of hepatitis E

In order to avoid contagion, some simple rules should be observed when visiting developing countries, such as

rinse vegetables and fruit thoroughly, taking care to peel the latter before consumption
consume meat and fish (especially shellfish) only after generous cooking.
boil water taken from the tap or common springs for at least 5-10 minutes; bottled water, on the other hand, can be consumed with more peace of mind, provided it is opened visibly. Attention should also be paid to ice cubes – which should never be consumed directly or added to drinks – and to water used for brushing one’s teeth: it too should be safe, hence bottled. Finally, when bathing in rivers and seas, care should be taken that no water enters the mouth.

The above measures should always be accompanied by common rules of personal hygiene, such as thorough and frequent hand washing, especially after going to the toilet and before touching food.

Finally, items such as toothbrushes, cutlery, glasses and towels should be for personal use only.

In addition to humans, the HEV virus also affects some animals, including pigs and deer.

Episodes of infection transmission have been observed after the consumption of raw meat from wild boar and deer; however, the real danger of this possible route of infection remains to be clarified.

In any case, the consumption of pork is strongly recommended only after adequate cooking (a measure that is also useful in preventing other diseases, such as toxoplasmosis).

Diagnosis and treatment of the virus

The clinical picture of Hepatitis E undoubtedly overlaps with other forms of hepatitis.

For this reason, several laboratory tests are necessary, the combination of which is capable of returning a correct diagnosis.

In addition to the PCR determination of viral RNA in blood or faeces (a method suggested for the early stages of infection), the serological determination of IgA/IgG/IgM class antibodies directed against the hepatitis E virus is the most important means available to confirm HEV infection.

Specifically, IgM class antibodies indicate an ongoing infection, whereas IgG class antibodies may be present in the acute phase or months or years after recovery.

The symptoms caused by hepatitis E, as seen, generally last a few weeks and tend to diminish over time until they disappear.

Treatment simply consists of adequate rest and a specific diet of light, fat-free foods until complete recovery.

In more severe cases, the use of anti-viral drugs such as ribavirin has been tried with some success.

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