Hepatitis E Virus What Is It? Risk of Liver Failure & Death 2025

Hepatitis E virus (HEV) infection is a common public health concern in many regions, particularly in countries with inadequate sanitation systems. Transmission primarily occurs through contaminated food and water. While most cases resolve spontaneously, high-risk groups such as pregnant women and individuals with pre-existing liver disease face a significant risk of developing severe complications, including acute liver failure. Understanding the causes, symptoms, diagnostic approaches, treatment options, and preventive measures of hepatitis E is essential for safeguarding one’s health and reducing the risk of infection.

What is Hepatitis E Virus (HEV)?

Hepatitis E Virus (HEV) is an RNA virus that causes acute inflammation of the liver. Transmission primarily occurs through ingestion of contaminated food or water. It is prevalent in countries with poor sanitation and is capable of causing community-wide outbreaks.

HEV was first recognized in the 1980s during outbreaks in India and Central Asia. It was later confirmed as an RNA virus belonging to the Hepeviridae family, which differs from other hepatitis viruses (A, B, C, and D).

Public Health Importance

The World Health Organization (WHO) estimates that more than 20 million HEV infections occur annually, with around 3 million symptomatic cases. The disease is especially concerning in Asia and Africa. In Thailand, studies have reported high prevalence rates among blood donors, underscoring the need for effective monitoring and prevention.

How is Hepatitis E Transmitted?

Transmission through Food and Water

Hepatitis E virus is most commonly transmitted via the fecal-oral route, particularly through contaminated food and water. Areas with poor sanitation are at higher risk, as unboiled water or improperly prepared food can serve as direct sources of infection.

Zoonotic Transmission from Animals

There is strong evidence that HEV can also spread from animals to humans. Pigs, deer, and other livestock serve as reservoirs, and consumption of undercooked meat—especially pork—has been identified as a major risk factor in several countries, including parts of Asia and Europe.

Transmission via Blood Transfusion and Organ Transplantation

Although less common, HEV can also be transmitted through blood transfusion and organ transplantation. This is particularly concerning for immunocompromised patients. Research in Thailand has detected HEV in some blood donors, underscoring the need for screening policies in transfusion medicine.

Symptoms of Hepatitis E Infection

Incubation Period

The incubation period of hepatitis E typically ranges from 2 to 6 weeks after exposure. During this phase, most patients are asymptomatic, which increases the risk of unintentional transmission.

General Symptoms

Once symptoms appear, they are often similar to other viral hepatitis infections and may include:

• Fever and fatigue
• Nausea and vomiting
• Loss of appetite
• Abdominal pain, particularly in the right upper quadrant
• Muscle and joint aches

Hepatic Symptoms

As the virus directly affects the liver, more specific signs of hepatitis may develop:

• Jaundice (yellowing of the skin and eyes)
• Dark-colored urine
• Pale or clay-colored stools
• Enlarged and tender liver upon examination

Severe Manifestations

While most patients recover within weeks without complications, severe disease can occur, especially in pregnant women and immunocompromised individuals. Possible outcomes include:

• Acute liver failure
• Hemorrhagic complications
• Encephalopathy (particularly in immunocompromised patients) These complications can be fatal if not managed appropriately.

Why Are Pregnant Women at Higher Risk from Hepatitis E?

Immunological Changes During Pregnancy

During pregnancy, a woman’s immune system undergoes adaptations to prevent rejection of the fetus. These changes result in reduced immune defense, making pregnant women more vulnerable to severe progression when infected with hepatitis E virus.

Maternal Complications

HEV infection in pregnancy, particularly in the third trimester, is associated with a markedly higher risk of acute liver failure compared to the general population. Maternal mortality rates are significantly elevated, and complications such as hemorrhage and sepsis are more likely to occur.

Fetal and Neonatal Risks

The impact of HEV in pregnancy extends to the unborn child. Infection may lead to miscarriage, premature delivery, or stillbirth. Vertical transmission of the virus from mother to fetus has also been reported, resulting in neonatal hepatitis and increased infant mortality.

How is Hepatitis E Diagnosed?

Serological Tests

Blood tests are commonly used to detect antibodies against HEV:

• Anti-HEV IgM: Indicates acute or recent infection.
• Anti-HEV IgG: Suggests past exposure or immunity from previous infection.

Molecular Detection

The most reliable method is detecting HEV RNA in blood or stool using RT-PCR. This confirms active infection and is particularly important for immunocompromised patients, who may develop chronic infection.

Antigen Detection

Some laboratories also perform HEV antigen tests, which provide faster confirmation. However, this method is not as widely implemented as antibody or RNA testing.

Importance of Screening High-Risk Groups

HEV testing is especially crucial in pregnant women, transplant recipients, and blood donors. Without proper screening, severe complications or silent transmission through transfusion may occur.

How is Hepatitis E Treated?

Supportive Care

Most hepatitis E cases are self-limiting and resolve spontaneously. Treatment is mainly supportive, focusing on adequate rest, hydration, and avoidance of hepatotoxic drugs such as high-dose acetaminophen or medications not recommended by physicians.

Antiviral Therapy in Special Cases

Currently, there is no universally approved antiviral therapy for hepatitis E. However, Ribavirin has been used in selected cases, particularly in immunocompromised patients or those with chronic HEV infection, under specialist supervision.

Management of High-Risk Groups

• Pregnant women: Require close hospital monitoring due to a significantly higher risk of acute liver failure and mortality.
• Transplant recipients and immunocompromised patients: May need adjustments of immunosuppressive therapy and regular HEV RNA monitoring.

Prevention of Complications

Another critical aspect of management is preventing complications such as acute liver failure, hemorrhage, or neurological manifestations. This requires multidisciplinary care in specialized medical centers.

Possible Complications of Hepatitis E Infection

Acute Liver Failure

One of the most severe complications of HEV infection is acute liver failure, particularly in pregnant women and individuals with pre-existing chronic liver disease. Without prompt medical intervention, this condition can be fatal.

Chronic Infection

Although hepatitis E typically causes acute disease, immunocompromised patients—such as organ transplant recipients or those receiving immunosuppressive therapy—may develop chronic HEV infection. This can progress to cirrhosis and long-term liver failure.

Extrahepatic Manifestations

Beyond liver involvement, HEV infection has been associated with complications in other systems, including:

• Neurological: Peripheral neuropathy, Guillain-Barré syndrome, encephalitis
• Hematological: Thrombocytopenia, leading to abnormal bleeding
• Renal: HEV-associated glomerulonephritis and other kidney dysfunctions

Long-Term Consequences

Survivors of severe HEV complications may experience long-term impairment of liver function. This places them at risk of developing cirrhosis or hepatocellular carcinoma, necessitating careful long-term medical follow-up.

Differences Among Hepatitis A–E Viruses

Comparison Table of Hepatitis Types

How to Prevent Hepatitis E

Safe Food and Water Practices

• Drink boiled or properly filtered water.
• Avoid consumption of raw or undercooked meat, especially pork, offal, and wild game that may harbor HEV.
• Wash vegetables, fruits, and fresh produce thoroughly before eating.

Personal Hygiene

• Wash hands regularly with soap and clean water, especially before meals and after using the toilet.
• Use clean utensils and avoid cross-contamination in food preparation.

Public Health Measures

• Ensure proper sewage disposal and sanitation systems to minimize contamination in communities.
• Regular monitoring of food and water quality in high-risk areas.
• Screening of blood donors in certain countries to prevent transfusion-related transmission.

Vaccination

A vaccine against hepatitis E (Hecolin) has been developed and licensed in China, but it is not widely available globally, including Thailand. Therefore, the cornerstone of prevention remains safe hygiene practices and proper food and water safety.

Is There a Vaccine for Hepatitis E?

Vaccine Development

The most notable hepatitis E vaccine developed to date is Hecolin (HEV 239 vaccine), a recombinant protein vaccine first produced in China. It was licensed for use in 2011 after demonstrating protective efficacy in clinical trials.

Current Use

Hecolin is currently used in limited regions of China, particularly in areas with high prevalence or outbreaks of HEV. Clinical studies have shown good protective efficacy, but the vaccine has not yet been widely adopted outside China.

Reasons for Limited Global Adoption

• Limited safety and efficacy data in pregnant women and immunocompromised patients.
• The World Health Organization (WHO) has not recommended widespread vaccination, except for outbreak settings or high-risk groups.
• Most countries, including Thailand, do not currently include the vaccine in their public health programs.

Future Prospects

Ongoing research is evaluating long-term safety and broader clinical applications of Hecolin, as well as the development of newer HEV vaccines. With stronger evidence, broader global adoption may be possible in the future.

Hepatitis E Transmission Through Blood Donation

Risk of Transfusion-Transmitted Infection

Although hepatitis E is predominantly transmitted through contaminated food and water, documented cases of transfusion-related transmission have been reported. This risk is heightened in countries without routine screening of blood donations for HEV.

Research Findings in Thailand

Studies in Thailand have detected HEV antibodies and RNA in blood donors, with prevalence rates as high as 29.7%. This figure is significantly higher compared to many regions in Asia and Europe, suggesting that blood transfusion in Thailand may carry a hidden risk of HEV transmission.

Impact on Vulnerable Patients

Transfusion-transmitted HEV is particularly dangerous for:

• Immunocompromised patients, such as organ transplant recipients
• Patients with chronic illnesses, especially liver disease
• Pregnant women requiring blood transfusion

Preventive Measures

Several countries have implemented HEV RNA screening for blood donors as a preventive measure. In Thailand, feasibility studies are still required to determine the cost-effectiveness and practicality of introducing nationwide HEV screening in blood transfusion services.

Hepatitis E in Immunocompromised Patients

Risk of Chronic Infection

While hepatitis E is usually an acute and self-limiting illness in healthy individuals, immunocompromised patients—such as organ transplant recipients or those on long-term immunosuppressive therapy—are at risk of developing chronic HEV infection. In such cases, the virus persists in the body, leading to ongoing liver inflammation.

Impact on Liver Health

Chronic HEV infection in immunocompromised individuals can rapidly progress to cirrhosis or chronic liver failure within a few years. This outcome is notably different from the usual course of acute, self-limiting disease in the general population.

Management and Monitoring

Caring for this group requires close medical supervision, including:

• Repeated testing for HEV RNA to monitor viral persistence
• Adjustment or reduction of immunosuppressive medications when clinically feasible
• Consideration of Ribavirin therapy, which has shown efficacy in some cases but must be prescribed under specialist care

Hepatitis E Situation in Thailand

Prevalence of Infection

Studies in Thailand have revealed that certain populations—particularly in rural areas with limited sanitation—show notable exposure to hepatitis E virus (HEV). Research also reports a higher-than-expected prevalence of HEV antibodies among blood donors, indicating silent circulation of the virus within communities.

Risk Factors in Thailand

• Consumption of undercooked or raw food, such as pork liver salad (“larb” or “koi muu”), which may be contaminated with HEV
• Inadequate wastewater treatment systems in some regions, leading to contamination of water sources
• Occupational risk among pig farmers and those in direct contact with livestock
  Public Health Challenges

Although most HEV infections in Thailand are mild and self-limiting, severe cases can occur—especially in pregnant women and individuals with chronic conditions. Current surveillance faces challenges, as HEV infections often present with non-specific symptoms and not all hospitals routinely perform HEV RNA testing.

Prevention and Public Health Approaches

Individual-Level Prevention

• Avoid consumption of raw or undercooked food, especially pork liver and other high-risk dishes
• Drink only boiled or properly filtered water
• Maintain personal hygiene practices, such as handwashing before meals and after using the toilet

Community-Level Prevention

• Improve wastewater treatment and sanitation systems in vulnerable areas
• Promote food safety campaigns to encourage the consumption of well-cooked meals, particularly in rural and high-risk regions
• Expand HEV screening among blood donors to minimize transfusion-related transmission

Vaccine Development

A hepatitis E vaccine (HEV 239 vaccine) has been developed and licensed in some countries, such as China. However, it has not yet been widely adopted globally and is not currently available in Thailand.

Public Health Recommendations

The World Health Organization (WHO) highlights the importance of HEV surveillance, particularly among high-risk groups like pregnant women, and emphasizes the role of improved sanitation infrastructure as the cornerstone of prevention.

Research and Scientific Advances in Hepatitis E

Vaccine Development

• The HEV 239 vaccine has been developed and licensed in countries like China, demonstrating high efficacy in preventing HEV infection.
• Efforts are underway to evaluate the feasibility of expanding its availability worldwide, though regulatory and accessibility barriers remain.

Diagnostic Innovations

• Real-time PCR technology has significantly improved the accuracy and speed of detecting HEV RNA.
• Ongoing studies aim to develop rapid and easy-to-use diagnostic kits suitable for rural and resource-limited settings.

Pathogenesis and Immunology

• Researchers are investigating interactions between HEV and the immune system, focusing on T-cell responses and cytokine activity.
• Genetic factors linked to an increased risk of acute liver failure in specific populations, such as pregnant women, are being explored.

Emerging Therapeutic Options

• Antiviral drugs like ribavirin have shown promising outcomes in chronic HEV cases, particularly among immunocompromised patients.
• Novel agents targeting HEV directly are under development, aiming to provide safer and more effective treatment alternatives.

Frequently Asked Questions (FAQ) about Hepatitis E

How is hepatitis E transmitted?

HEV spreads primarily through contaminated food, water, and contact with fecal matter containing the virus.

What are the symptoms of hepatitis E?

Common symptoms include fever, fatigue, muscle aches, nausea, vomiting, and jaundice (yellowing of the skin and eyes).

How severe is hepatitis E infection?

Most cases resolve spontaneously, but pregnant women and individuals with chronic liver disease are at high risk of acute liver failure, which can be life-threatening.

Can hepatitis E be treated?

There is no specific antiviral treatment for acute HEV. Supportive care is usually provided, but ribavirin has been used in chronic infections among certain patients.

Is there a vaccine for hepatitis E?

Yes, the HEV 239 vaccine has been developed and approved in certain countries, though it is not yet widely available worldwide.

How does hepatitis E differ from other types of viral hepatitis?

It is mainly transmitted via contaminated food and water, and carries higher risks for pregnant women compared to other hepatitis viruses.

Conclusion

Hepatitis E is often overlooked but poses a serious health risk, especially for vulnerable populations. Although most infections resolve without specific treatment, prevention remains the most effective strategy. Ensuring access to safe food and clean water, along with strict hygiene practices, plays a crucial role in controlling the spread of HEV. While a vaccine exists in some countries, it is not widely available, making awareness and prevention key factors in reducing hepatitis E infection rates worldwide.

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