Introduction

Although the liver is not always given as much attention as the brain and heart, this organ performs critical functions in your body. These include body detoxification, bile and cholesterol production, blood filtration, etc. The fact that the liver is involved in these essential processes implies that any injury or damage to this organ can trigger a cascade of negative consequences. 

However, besides injury, the liver can have a high affinity for viral infections. The viruses that can affect the liver are called hepatitis viruses. There are five different types of hepatitis virus that can damage the liver; (A, B, C, D and E). Hepatitis is a condition characterised by inflammation of the liver and can be caused by viruses, autoimmune diseases and excessive alcohol intake. This article gives a comprehensive overview of the differences in terms of symptoms and transmission between hepatitis E and hepatitis A. 

Definition of hepatitis E and hepatitis A

Hepatitis E is an inflammation of the liver caused by the hepatitis E virus (HEV). HEV is a spherical, non-enveloped, single-stranded RNA virus that is part of the Hepevirus genus and Hepeviridae family.¹ HEV infection was first described in 1980 after the analysis of the blood samples from patients plagued by the acute hepatitis epidemic in India between 1955 and 1956 spread by contaminated water.²  The causative agent was later identified in 1983 and named E due to its enteric and endemic features.² HEV can cause both acute hepatitis and if your immune system is compromised, chronic hepatitis. 

Hepatitis A is a liver condition caused by hepatitis A virus (HAV). HAV is a small, single-stranded RNA virus that is part of the Picornaviridae family and a member of the genus Hepatovirus.³ HAV has 6 genotypes;³ of these infect humans while the remaining 3 infect simians.⁴ The species infected by the 3 genotypes of HAV include bats, hedgehogs, shrews, and rodents. However, a zoonotic reservoir for HAV no longer exists. HAV is the major cause of acute and self-limiting hepatitis in humans worldwide.⁴

Epidemiology of HEV and HAV 

HEV is a common cause of hepatitis in many African countries including Asia. There are 4 researched genotypes of HEV that can cause infection in humans.⁵ Genotypes 1 and 2 affect human beings alone. They can be transmitted via the faecal-oral route and can survive in water. As a result, the places with the highest prevalence of HEV infection are in places that are unsanitary and overcrowded. Thus, HEV is endemic in developing countries with genotype 1 being the most common cause of outbreaks.⁶ HEV genotypes 3 and 4 affect both animals and humans and are commonly seen in developed countries. According to the World Health Organization, there are approximately 20 million infections caused by HEV annually, leading to 3.3 million symptomatic cases and an estimated 44,000 deaths.

The prevalence of HAV infection varies widely in different parts of the world.⁷ This is because it is primarily determined by socioeconomic factors. Thus, the epidemiology of HAV depends on the genotype involved and the geographical area under surveillance. 

One essential fact about HAV infection is the epidemiological shift that occurs in industrialised countries which causes an increase in morbidity and mortality associated with HAV.⁷ This is because since HAV infection confers lifelong immunity, children in poor resource areas with high endemicity don’t have recurrent HAV infection and the spread is contained.⁷ On the contrary, in high-income regions with low endemicity, exposure to HAV infection is rare. Consequently, a small proportion of people have anti-HAV antibodies. Therefore, if HAV is introduced, a significant outbreak ensues particularly in high-risk groups such as homosexual men, drug users and the homeless.⁸

Core differences between hepatitis E and hepatitis A 

Hepatitis E and Hepatitis A cause enterically transmitted infections. Although both are similar in terms of their viral genome, there are differences in the symptoms and route of transmission. 

Differences in symptoms

Hepatitis E: The incubation period from hepatitis E infection to the manifestation of symptoms ranges from 2-8 weeks.⁷ However, the initial symptoms of acute hepatitis E can be unspecific and include the following; 

• Flu-like myalgia
• Arthralgia
• Weakness and vomiting 
• Abdominal pain
• Neurological symptoms such as peripheral neuropathy can also occur¹⁰ 

In developing countries where HEV genotypes 1 and 2 are prevalent, adults are commonly affected with hepatitis E infection. However, other at-risk groups include children below 3 years of age, individuals with pre-existing liver conditions such as cirrhosis and pregnant women.⁷

Hepatitis A: The clinical symptoms occur after an incubation period of 14-28 days which ranges from asymptomatic to severe hepatitis.⁹ These symptoms appear to be more severe with increasing age and young children are usually asymptomatic. The clinical presentation involves 2 phases;

• Prodromal phase: This lasts for 3-10 days and is characterised by malaise, muscle aches and pain⁷
• Icteric phase: This lasts 1-3 weeks and involves a combination of hepatic and cholestatic jaundice which is characterised by anorexia, nausea and fatigue⁷

The appearance of dark urine followed by jaundice and pale stool is the hallmark clinical features of hepatitis A. The severity of disease and mortality usually increases with age for HAV. This implies that age is the major risk factor for hepatitis A.⁷ 

Differences in transmission

Hepatitis E: Different from HAV, HEV infection can be zoonotic. This means that transmission can occur through the consumption of undercooked infected meat.¹² The consumption of infected retail pork products is the primary vector for human transmission. Other foods implicated in HEV isolation include shellfish, fruits and vegetables.¹¹ Hepatitis E can also be transmitted via blood transfusion, solid organ transplant and vertically from mother to child.¹² However, the major route of transmission is water contaminated with faeces.⁷ 

Hepatitis A: The main route of transmission of HAV is via the faecal-oral route in developing countries and amongst high-risk groups. In developed countries, person-to-person transmission is common, unlike hepatitis E. The high-risk group include homosexual men, people who engage in oral-anal sexual contact, drug users, travellers to endemic countries and people with chronic liver disease.¹²

Two key distinguishing features between hepatitis E and hepatitis A are the fact that infection with HEV does not confer lifelong immunity while HAV infection typically confers lifelong immunity.⁷ Also, HEV has a high mortality rate in pregnant women in the third trimester which can develop into fulminant hepatic failure.¹³ This, however, is not seen in HAV infections.¹³

Management and prevention of hepatitis E and hepatitis A

Hepatitis E infection usually resolves spontaneously, hence supportive treatment is required. Immunosuppression is the major risk factor that can lead to the development of chronic HEV infection.⁷ Therefore, the first approach in treating chronic hepatitis E is to reduce immunosuppression, then commence treatment with ribavirin or pegylated alpha interferon if the infection persists.⁷ Ribavirin is contraindicated in pregnancy due to increased risk of foetal loss and teratogenicity.⁷ 

In developing countries with HEV genotypes 1 and 2 are endemic, prevention strategies include improving sanitation facilities and having access to safe drinking water.⁷ Since HEV can exist in zoonotic hosts, adequate cooking of animal products is the primary preventive measure of transmission. Individuals who work in animal surroundings should observe proper hygiene practices.¹¹ 

There is no specific treatment regimen for hepatitis A. Management of HAV infection involves adequate fluid intake, rest and monitoring of immunocompromised patients at risk of developing complications. The spread of HAV can be contained by observing good hygiene practices, sanitation and post-exposure prophylaxis which provides short-term immunity. However, there are effective and safe vaccines for hepatitis A and a combined vaccine for HAV and hepatitis B which have been approved.⁷

Diagnosis of hepatitis E and hepatitis A

The diagnosis of hepatitis E depends on the clinical presentation and elimination of other causes of hepatitis, particularly hepatitis A and hepatitis B. It involves the detection of IgM and IgG anti-HEV antibodies in the serum by ELISA and the identification of HEV RNA by PCR in serum or stool samples. Specifically, IgM anti-HEV antibodies are detected in the first few months after infection with HEV, while IgG anti-HEV antibodies are seen in either recent or remote exposure.⁷ 

Similarly, the diagnosis of hepatitis A depends on the identification of IgM anti-HAV. this is typically present in the serum for 3-6 months from the onset of symptoms.¹⁴ However, positive detection of IgG anti-HAV in the absence of IgM anti-HAV is indicative of past exposure to HAV and subsequent life-long immunity to the virus.¹⁴ 

FAQs

What are the complications of hepatitis E and hepatitis A?

In rare cases, hepatitis E can be chronic and lead to fulminant hepatitis. Particularly, pregnant women in their third trimester with hepatitis E have a higher risk of acute liver failure and mortality. Hepatitis A can be severe in individuals older than 50 years of age or with an underlying liver condition. In these cases, it may lead to liver failure if not managed. 

Can hepatitis E and hepatitis A occur together?

Co-infection with HEV and HAV can occur with a high mortality rate due to increased risk of acute liver failure both in children and adults. 

Can hepatitis E be resolved completely? 

Hepatitis E is usually self-limiting and proper management techniques outlined above are adequate for patients to make a full recovery. Long-term liver problems rarely occur unless the person has an underlying liver condition or is immunocompromised. 

Summary

• Hepatitis E and hepatitis A are enteric conditions caused by HEV and HAV respectively with strong affiliation for the liver. It can cause inflammation and lead to acute or chronic hepatitis. 
• HEV has a wide variety of zoonotic hosts where transmission can occur via the consumption of contaminated or undercooked meat. The major route of transmission is water contaminated with faeces.
• HAV only infects humans and occasionally, non-human primates and can be transmitted mainly via the faecal-oral route. 
• The symptoms associated with hepatitis E and hepatitis A infection are somewhat similar. However, the incubation period of HEV is longer than that of HAV. 
• Preventive measure of hepatitis E and hepatitis A involves implementing good hygiene practices before and after dealing with farm products and having access to clean drinking water.