Introduction

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV) and is part of the hepatitis family.¹ The hepatitis family is characterised by the inflammation of the liver, and there are five different types of infection: A, B, C, D and E.³ HEV is the most common cause of acute (short-term) viral hepatitis globally.^1,2 Hepatitis E is generally a mild short-term infection that does not require any medical treatment; however, it can be serious in pregnant women and individuals who have a weakened immune system.³ There is no vaccine for hepatitis E.³

Global Prevalence

According to the World Health Organisation (WHO), HEV infection causes approximately 20 million infections and results in over 55,000 deaths annually.^4,5 It is most prevalent in areas where sanitation is poor and access to clean drinking water is limited, such as in Africa and Asia.¹ However, HEV prevalence appears to be increasing in parts of Europe, but declining in the United States. HEV is now the most common cause of acute hepatitis in the United Kingdom.³ The aim of this article is to explain the common symptoms of hepatitis E infection that individuals may experience.

Understanding Hepatitis E

Virus

HEV belongs to the Orthohepevirus genus (group of viruses), part of the Hepeviridae family.⁴ The hepatitis E virus (HEV) is a non-enveloped (does not have an outer fatty layer, making it highly resistant to disinfectants), single-stranded ribonucleic acid (RNA) virus, approximately 27-34 nanometres (nm) in diameter. Scientists have discovered four types of HEV: genotypes 1 to 4.⁴

Genotypes 1 and 2

HEV genotypes 1 and 2 are pathogenic towards humans only (human viruses) and are transmitted through the faecal-oral route, predominantly found in developing countries.⁶ Genotype 1 strains are typically present in India, China, Bangladesh, Nepal, Pakistan, Afghanistan and most countries in sub-Saharan Africa.⁶ Genotype 2 strains are present in Nigeria, Chad, Sudan, Mexico and the Central African Republic.⁶

During outbreaks, the incidence of HEV genotypes 1 and 2 is highest in adolescents and adults (15-40 years of age).⁴ Younger children under age 10 appear to have lower rates of infection.^6,7 HEV prevalence in young children is poorly understood; however, it is suggested that they may consume less contaminated water than adults, reducing their exposure to hepatitis E.⁶

Genotypes 1 and 2 typically cause a self-limited acute infection that does not progress to a chronic infection,⁴ with an overall mortality rate of 1%.⁶ HEV in pregnant women often leads to premature births and infant mortality, with a mortality rate among pregnant women of 30% or greater.^4,6 Transmission of HEV from mother to child has been documented, leading to rare neonatal hepatitis E.^4,12,13 The mechanisms regarding increased HEV severity in pregnant women and its impact on the fetus are not fully understood, but hormonal changes and immune modulation during pregnancy have been suggested to increase the severity of the infection.⁴

Genotypes 3 and 4

HEV genotypes 3 and 4 are zoonotic infections (found and transmitted through animals) and are more common in industrialised, developed and high-income countries such as the United States, Australia and Japan.^4,8 Genotypes 3 and 4 typically affect adults aged 40 years or older and result in clinically silent acute infections in immunocompetent individuals.^4,8 Less than 2% of those infected with HEV genotypes 3 and 4 are symptomatic.^7,8,9

Chronic hepatitis can develop in immunosuppressed individuals, including those who have received organ transplants (kidney, lung, heart, etc.), individuals with human immunodeficiency virus (HIV) and individuals undergoing chemotherapy to treat blood cancers, and as a result may progress to life-threatening liver cirrhosis (permanent damage and scarring of the liver).^8,10 A 2017 study described 93 cases of asymptomatic HEV genotype 3 and 4 infection and determined that male sex and older age were risk factors for symptomatic HEV disease.^8,11

Transmission

HEV is mainly transmitted through the faecal-oral route in the developing world,^1,4 found in the stool of people infected with the virus.² In developing countries, the virus can be spread by people drinking water contaminated by faeces from individuals infected with the virus.² HEV infection usually results in asymptomatic, self-limited infection in approximately 95% of affected immunocompetent individuals.^1,2,4 In the developed world, HEV is typically acquired through zoonotic infection, where people have become ill with hepatitis E after consuming raw or undercooked pork, wild boar meat, venison (deer) or shellfish, resulting in food-borne cases of HEV infection.^1,2,3

Incubation Period and Early Signs

After HEV is ingested (through contaminated water or undercooked meat), it passes through the gastrointestinal mucosa (gut) and into the liver.⁴ The virus enters the liver cells, releases its genetic material (RNA) and replicates itself.⁴

The incubation period (the period of time an individual can have the infection before experiencing any symptoms)¹⁴ following exposure to genotypes 1 to 4 of HEV ranges from 2-10 weeks, with an average period of 5-6 weeks.⁵ An individual infected with HEV can pass the virus in their stool, starting a few days before symptoms appear (if they display symptoms) and continuing for up to 3-4 weeks after the onset of illness.⁵

There are three phases of hepatitis E. Non-specific early (known as the prodromal phase) symptoms of HEV include:^14,16

• Mild fever
• Joint pain
• Oedema (swelling)
• Rash

Common Symptoms of Hepatitis E Infection (HEV)

Common symptoms during the second stage of hepatitis E (preicteric phase) include:^4,15,16

• Tiredness or fatigue
• Dark urine
• Pale or clay-coloured stools
• Abdominal pain
• Diarrhoea
• Cough
• Fever
• Nausea and vomiting
• Loss of appetite (anorexia)
• Itching
• Enlarged liver
• Malaise and weakness, typically accompanied by fever and anorexia
• Joint or muscle pain (myalgia)

If you are experiencing any of the symptoms mentioned, please contact your healthcare provider.

In addition to symptoms exhibited during the early and second stage phases, common symptoms during the third phase (icteric phase) of hepatitis E infection include:^4,15,16

• Jaundice (yellowing of skin and eyes), the most prevalent symptom (observed in two-thirds of cases)⁴
• Enlarged, tender liver (known as hepatomegaly)⁵
• Anorexia, nausea, vomiting and myalgia symptoms may worsen
• Irritated skin lesions may develop

Severity of Symptoms and Diagnosis

Symptoms of HEV typically last 1-6 weeks, and most cases are mild and do not require medical treatment.⁵ In rare cases, hepatitis E can be severe and result in acute liver failure (fulminant hepatitis) and death.⁵ HEV poses a higher risk in certain individuals:^5,20

• Pregnant women, particularly those in the second or third trimester (20-25% mortality rate)
• Individuals with a pre-existing liver condition, as HEV can cause additional damage²⁰
• Individuals who are immunosuppressed due to a medical condition or organ transplant

There is now some scientific evidence that hepatitis E may cause problems in other parts of the body as well as the liver, although these are very rare cases.¹⁷ A link has been discovered between HEV and glomerulonephritis, a kidney condition where the glomeruli (tiny filters inside the kidneys) become damaged.^17,18 Some individuals with HEV can develop a blood condition called thrombocytopenia, when there are not enough platelets (small blood cells that help with blood clotting and wound healing) present in the blood.^17,19 The British Liver Trust also states that HEV has links with neurological conditions such as neuralgic amyotrophy and Guillain-Barré syndrome.¹⁷

Hepatitis E is not clinically distinguishable from other types of viral hepatitis or other diseases that cause jaundice.⁵ However, definitive diagnosis can be confirmed by laboratory tests based on the detection of anti-HEV immunoglobulin M antibodies found in the individual's blood.⁵ Reverse transcriptase polymerase chain reaction (RT-PCR) can also be used to detect HEV RNA in blood and stool samples, although this method requires specialised laboratory facilities.^4,5

Summary

Hepatitis E is a liver disease caused by the hepatitis E virus (HEV), characterised by the inflammation of the liver. HEV is the most common cause of acute viral hepatitis globally and is most prevalent in areas with poor sanitation, such as sub-Saharan Africa and parts of Asia. There are four main types of hepatitis E, called genotypes 1 to 4. Hepatitis E can be transmitted through the faecal-oral route (drinking contaminated water; typically genotypes 1 and 2) or via zoonotic infection (eating undercooked or raw meat; typically genotypes 3 and 4).

Hepatitis E is generally a mild short-term infection that does not require any medical treatment; however, it can be severe in pregnant women and individuals who have a weakened immune system or a pre-existing liver condition. Early symptoms of HEV typically include flu-like symptoms (such as mild fever and joint pain), progressing to common symptoms such as jaundice, abdominal pain, dark urine, fatigue, nausea and loss of appetite. If you are experiencing any symptoms mentioned in this article, it is recommended that you consult your healthcare provider.