What is Hepatitis E?
Hepatitis E virus, or HEV, is the most common cause of sudden viral liver inflammation worldwide. However, because its symptoms are quite general and the disease usually resolves on its own, it is often not diagnosed. Hepatitis E virus belongs to the Orthohepevirus group, which is part of the Hepeviridae family. It’s a certain type of virus that doesn’t have an outer coating, and it carries a single-strand of RNA.
The virus is primarily spread by coming into contact with feces, then consuming it by accident. It typically causes a temporary and self-resolving liver inflammation in healthy hosts. However, it can cause long-term liver inflammation in those with weakened immune systems. It has a higher death rate as compared to Hepatitis A, which is also spread in the same way. Pregnant women face a high mortality rate if they get infected with the Hepatitis E virus.
The first time a viral liver inflammation different from Hepatitis A was identified was during a waterborne hepatitis outbreak in late 1970s in Kashmir, India. It was initially named as a distinct type of hepatitis that was not Hepatitis A or B. It was later called Hepatitis E, aligning it with the naming system of other hepatitis viruses.
What Causes Hepatitis E?
The Hepatitis E virus (HEV) is a type of virus which cannot be seen by naked eyes and consists of single-strand RNA. There are four varieties of this virus, named genotypes 1 through 4.
Genotypes 1 and 2 are typically found in humans and are most often spread through contaminated water, especially in developing countries like parts of Africa, Asia, Central America, and the Middle East. This typically happens when the virus ends up in the mouth from fecal matter.
Meanwhile, Genotypes 3 and 4 primarily occur in animals, specifically those that humans eat like pork and deer. These types of the virus are mainly located in developed countries, such as USA, Australia, Japan, and China. People usually get these genotypes by eating the undercooked meat of these animals.
Young adults (aged 15-40) are commonly affected by Genotypes 1 and 2. They generally cause temporary infections that do not lead to chronic disease. However, these infections can be more severe in pregnant women or in people already suffering from chronic liver disease, potentially leading to a life-threatening condition called fulminant liver failure.
Genotypes 3 and 4, on the other hand, are more likely to affect older adults (over 40) and can sometimes result in chronic disease, especially in individuals whose immune systems are weak, including those who have been through organ transplants or sufferers of HIV/AIDS.
Risk Factors and Frequency for Hepatitis E
Hepatitis E virus (HEV), as per the World Health Organization (WHO), is responsible for approximately 20 million new infections each year and over 55,000 deaths. Despite being a global concern, HEV is especially common in underdeveloped countries. The virus is most frequently found in Asia, Africa, the Middle East, and Central America, making it the second leading cause of sporadic hepatitis in North Africa and the Middle East.
In Western countries, most cases of HEV are seen among travelers who have visited areas where the virus is widespread. From 2009 to 2010, it was estimated that around 6% of the US population had HEV. Several factors increase the risk of having HEV antibodies such as getting older, origin outside of the United States, being of Hispanic race, and eating meat more than 10 times a month are all associated with a higher likelihood of HEV seropositivity.
Previously, HEV was thought to only be rampant in developing countries like those in Asia and Africa, but more recent findings suggest that it is also common in affluent countries in Europe. In these countries, the disease is zoonotic, meaning humans often acquire it from pigs.
Signs and Symptoms of Hepatitis E
Hepatitis E virus (HEV) often results in an acute illness similar to other types of acute hepatitis. Most patients may not show symptoms, or they may experience mild symptoms. These can include feeling unwell or unusually tired, loss of appetite, nausea, vomiting, yellowing of the skin and eyes (jaundice), and abdominal pain. When examined by a doctor, patients might look ill and jaundiced; they may also have abdominal tenderness and an enlarged liver.
HEV should be thought of as a possible culprit if a patient with symptoms of acute hepatitis is from or has recently traveled to a country where HEV cases are high. Adults are more commonly affected than children. Pregnant women tend to have more severe symptoms. Generally, HEV is a self-limiting sickness in healthy individuals, meaning it usually resolves on its own. However, in patients with impaired immune systems like transplant recipients, the infection could become chronic and potentially lead to a severe liver disease called cirrhosis.
In severe cases, Hepatitis E could turn into fulminant hepatitis, resulting in a fatality rate between 0.5% and 3%. Additionally, patients may also experience other health issues including low platelet count, destruction of red blood cells, blood disorders, inflammation of the thyroid, kidney disease, and neurological conditions like acute transverse myelitis and meningitis caused by bacteria.
- Feeling unwell or unusually tired
- Loss of appetite
- Nausea
- Vomiting
- Jaundice (yellowing of the skin and eyes)
- Abdominal pain
- Abdominal tenderness
- Enlarged liver (sometimes)
Testing for Hepatitis E
When evaluating a patient with possible Hepatitis E virus (HEV), doctors need to be aware of certain factors. For instance, they should consider HEV if the patient has recently traveled, comes from a country where HEV is common, has acute liver inflammation, or is at increased risk for significant health complications like those with existing liver diseases, pregnant women, and people with weakened immune systems.
In the laboratory, a patient with HEV will usually have high levels of certain substances in their blood, such as bilirubin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Diagnosing HEV can be challenging because there is not a standard test. Some commercial tests check for antibodies in the blood that the body makes to fight the virus (anti-HEV IgM and IgG). But those tests can sometimes give a false positive or negative result.
A more accurate diagnosis is possible when the actual virus is detected in the blood or stool using PCR testing (polymerase chain reaction). However, because the virus may not stay in the blood for long, a negative HEV PCR test doesn’t rule out a recent HEV infection. Antibody tests may be more useful in these cases.
But for those with weakened immune systems, antibody tests might not work well. They should instead rely on PCR testing to help confirm a HEV infection. Chronic HEV infections are identified if the HEV RNA can still be detected in the blood or stool six months after the initial infection.
European liver disease guidelines from 2018 suggest using both antibody tests and PCR-based tests to diagnose acute HEV infections. For chronic HEV infections, they recommend PCR-based testing.
Treatment Options for Hepatitis E
When a person is infected with the Hepatitis E virus (HEV), it often clears up on its own and only requires patient comfort care. The body’s natural biochemical response will usually get back to normal anywhere from one to six weeks after the symptoms first start. However, if someone develops a very severe, life-threatening form of liver damage, known as fulminant liver failure, they will require a liver transplant.
The effectiveness of using antiviral medicine, such as ribavirin, for treating acute HEV infection in people with weak immune systems isn’t quite clear. It’s important to note that ribavirin should not be used in pregnant women who are diagnosed with acute HEV infection due to the risk of it causing birth defects.
For people whose immune systems are compromised and who have persistent HEV infection, tweaking the doses or types of medications that are suppressing their immune system and utilizing antiviral drugs (like ribavirin or peginterferon) are commonly suggested strategies.
What else can Hepatitis E be?
When a patient is being diagnosed, there are various conditions that doctors might consider, especially if the symptoms are similar. Some of these potential diseases include:
- Other types of viral hepatitis, like hepatitis A, B, or C
- Cytomegalovirus (CMV)—a common virus that can affect nearly anyone
- Drug or toxic hepatitis—a liver disorder caused by certain drugs or toxins
- Ischemic hepatitis—caused by insufficient blood flow to the liver
- Other diseases prevalent in certain areas, such as leptospirosis, dengue fever, yellow fever, and malaria
The doctor will carefully evaluate the patient’s symptoms to rule out these possibilities and reach an accurate diagnosis.
Possible Complications When Diagnosed with Hepatitis E
Usually, HEV (a type of liver infection) gets better on its own. However, in some patients, the disease may worsen and cause acute, or sudden, complications. These could be acute hepatic failure (extreme liver failure), cholestatic jaundice (a condition where bile flow from the liver is blocked), or chronic HEV infection (long-term liver infection). Certain extra-liver symptoms have been associated with HEV genotype 3. These are mostly related to the nervous system and include conditions such as inflammatory polyradiculopathy (nerve damage due to inflammation), Guillain-Barré syndrome (a rare neurological disorder), peripheral neuropathy (nerve damage in the extremities), encephalitis (brain inflammation), and ataxia (a neurological condition that affects muscle coordination).
Possible Complications of HEV:
- Acute hepatic failure
- Cholestatic jaundice
- Chronic HEV infection
Extra-liver symptoms linked to HEV genotype 3:
- Inflammatory polyradiculopathy
- Guillain-Barré syndrome
- Peripheral neuropathy
- Encephalitis
- Ataxia
