Hepatitis E Virus

Introduction

Hepatitis E Virus (HEV) is a major cause of acute viral hepatitis worldwide. It belongs to the Hepeviridae family and primarily spreads through contaminated water or undercooked meat.

While most cases are self-limiting, HEV infection during pregnancy can be extremely dangerous, leading to severe liver failure and high mortality rates. The virus affects millions of people globally each year, particularly in areas with poor sanitation and unsafe water sources.

Key Facts

• Virus Family: Hepeviridae (Genus: Orthohepevirus)
• Structure: Non-enveloped, icosahedral, single-stranded, positive-sense RNA (~7.2 kb)
• Human Genotypes: 1 to 4
• Genotypes 1–2: Spread via fecal–oral route (contaminated water)
• Genotypes 3–4: Zoonotic, transmitted through undercooked pork or wild game
• Incubation Period: 2 to 9 weeks
• High-Risk Groups: Pregnant women, immunocompromised individuals, travelers to endemic regions
• Vaccine: Available in China (HEV  239), not yet globally distributed

Keywords

Hepatitis E Virus (HEV), Fecal–Oral Transmission, Acute Hepatitis, Zoonotic Infection, Pregnancy Complications, Ribavirin, HEV Vaccine, Contaminated Water, Viral Hepatitis, Public Health.

Characteristics of HEV

HEV is a non-enveloped, icosahedral RNA virus with a genome size of about 7.2 kilobases. Its genome encodes several open reading frames (ORFs):

• ORF1: Enzymes for replication
• ORF2: Capsid protein
• ORF3: Helps in virus release from infected cells

The virus replicates within liver cells (hepatocytes) using host machinery and produces new viral particles that are released into the bloodstream and bile, ultimately exiting through feces.

Epidemiology

According to the World Health Organization (WHO), in 2021, there were approximately 19.5 million acute HEV infections globally, leading to about 3,450 deaths.

HEV is endemic in regions with limited access to clean water and sanitation, particularly in:

• South and East Asia
• Sub-Saharan Africa
• Middle East

Genotypes 3 and 4 cause sporadic cases in developed countries such as Europe and North America, mostly through undercooked pork or animal contact.

Pregnant women, especially during the second and third trimesters, face mortality rates up to 25% due to severe complications such as acute liver failure and stillbirths.

Transmission

HEV is transmitted primarily by the fecal–oral route, meaning infection occurs when contaminated food or water is consumed.

• Genotypes 1 & 2: Spread through contaminated drinking water and poor sanitation.
• Genotypes 3 & 4: Zoonotic; transmitted through undercooked pork, game meat, or organ meats.

Other rare transmission routes include:

• Blood transfusion
• Mother-to-child (vertical) transmission
• Organ transplantation in immunosuppressed patients

Maintaining clean water supplies and avoiding raw or undercooked meat are essential preventive steps.

Pathogenesis

HEV primarily targets the liver, causing inflammation and cell death. The virus itself is not highly cytopathic, meaning it doesn’t directly destroy liver cells. Instead, liver injury results from the immune system’s response to the infection.

In pregnant women, hormonal and immune changes increase viral replication and worsen inflammation, leading to fulminant hepatitis.

In immunocompromised patients (such as transplant recipients), HEV can become chronic, leading to long-term liver damage and even cirrhosis.

Immunity and Chronic Infection

Most healthy individuals recover fully from acute HEV and develop lifelong immunity through antibodies (anti-HEV IgG).

However:

• Chronic HEV can develop in immunosuppressed patients (organ transplant recipients, people on chemotherapy, or HIV-positive individuals).
• Reinfection is rare in healthy individuals.
• A recombinant HEV vaccine (HEV  239) based on genotype 1 exists in China, providing strong protection, though it’s not widely available worldwide.

Clinical Features and Symptoms

HEV infection typically appears 2–9 weeks after exposure.

Common symptoms include:

• Fever and fatigue
• Loss of appetite and nausea
• Abdominal discomfort
• Dark urine and pale stools
• Jaundice (yellowing of the eyes and skin)

Most cases last 2–6 weeks and resolve spontaneously.

Severe and Complicated Cases

• Fulminant hepatitis: In about 0.5–3% of cases
• Pregnancy: Mortality may reach 10–25%, especially in the third trimester
• Neurologic complications: Such as Guillain-Barré syndrome and neuropathies (5–10% of cases)
• Chronic infection: Seen only in immunocompromised individuals, leading to progressive liver damage and cirrhosis

HEV During Pregnancy

HEV poses a serious risk to pregnant women:

• Mortality rate may reach 25% in the last trimester.
• Infections can lead to miscarriage, stillbirth, or neonatal death.
• WHO estimates that 2,400–3,000 stillbirths per year are linked to HEV infection in developing countries.

Because ribavirin (the main antiviral option) is contraindicated in pregnancy, management is purely supportive.

Diagnosis

Diagnosis involves serological testing and molecular detection:

1.     Anti-HEV IgM: Appears early during acute infection — a primary diagnostic marker.

2.     Anti-HEV IgG: Indicates past infection or immunity.

3.     HEV RNA PCR: Confirms active infection; useful in immunocompromised patients where antibody response may be weak.

4.     Liver Function Tests: Elevated ALT and AST with mild ALP elevation indicate hepatitis.

Because symptoms mimic other types of hepatitis (A, B, C), specific testing is important for accurate diagnosis.

Treatment

Most cases of HEV require supportive care only:

• Rest, hydration, and nutritional support.
• Avoid alcohol and hepatotoxic drugs.
• Manage complications like coagulopathy or encephalopathy carefully.

Chronic or Severe HEV

• Ribavirin is effective for chronic HEV, especially in immunocompromised patients.
• Ribavirin therapy may last several months, but it is teratogenic and unsafe during pregnancy.
• For transplant patients, reducing immunosuppressive drugs combined with ribavirin can help clear the infection.

No specific antiviral therapy has been universally approved yet.

Prevention

The most effective way to prevent HEV infection is through good sanitation, safe water, and proper food handling.

Preventive Measures:

1.     Drink boiled or treated water, especially in high-risk regions.

2.     Avoid undercooked pork, game meat, and organ meats.

3.     Practice safe hygiene and handwashing.

4.     Screen blood products in endemic areas.

5.     HEV vaccination (HEV  239) — available in China, primarily used for outbreak control.

Currently, there is no global vaccine and no post-exposure prophylaxis available.

Conclusion

Hepatitis E Virus (HEV) is a leading cause of acute viral hepatitis, especially in developing regions with poor sanitation. While most infections resolve naturally, pregnant women and immunocompromised individuals face life-threatening complications.

Improving water quality, hygiene, and food safety are key public health measures. The availability of an HEV vaccine offers hope for prevention, but global access remains limited. Until then, education, sanitation, and early diagnosis are the most effective tools for controlling HEV worldwide.