• Hepatitis E Virus: Evolution, Clinical Impact, and Advances in Diagnosis, Treatment, and Prevention
  • Fatemeh Ansari,1 Arash Letafati,2,*
    1. Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.
    2. Department of Virology, Faculty of Public Health, Tehran University of Medical Sciences, Tehran, Iran


  • Introduction: Hepatitis E virus (HEV) produces acute viral hepatitis, which creates a worldwide health emergency. The virus exists as a single-stranded positive-sense RNA entity that belongs to the Hepeviridae family. Scientists have discovered eight different genotypes, including genotypes 1 and 2 that affect humans exclusively and genotypes 3, 4, and 7, which spread between humans and animals. Additionally, there are genotypes 5, 6, and 8, which affect animals exclusively. The primary mode of HEV transmission occurs through fecal-oral contamination of water sources. Still, the virus also spreads through eating undercooked meat and from mother to child and through blood contact. The body naturally fights most infections but people with weakened immune systems and pregnant women face dangerous outcomes including prolonged infections and severe liver failure. The review presents an overview of HEV, including its classification system and molecular characteristics and disease spread patterns and infection mechanisms and diagnostic methods and treatment options and prevention measures.
  • Methods: This paper is a narrative review synthesizing findings from epidemiological studies, clinical reports, phylogenetic analyses, and therapeutic trials. It compiles global data on HEV prevalence, transmission, and clinical outcomes, while also analyzing molecular insights such as HEV genome organization, microRNA regulation, and immune response. Evidence from case studies, systematic reviews, and meta-analyses is included to present a comprehensive overview of HEV biology and management. No new experimental or clinical data were generated by the authors.
  • Results: Epidemiology and Transmission: Studies estimate that about 12.5% of people worldwide have anti-HEV IgG antibodies in their blood. The general population experiences death rates between 0.5 and 4 percent but pregnant women face a much higher risk of death reaching 30 percent. Genotypes 1 and 2 cause major outbreaks in developing nations because they spread through water that contains contamination. The developed nations experience sporadic cases of genotypes 3 and 4 because these strains enter the population through infected food that comes from animal sources. Pathogenesis and Clinical Features: HEV usually appears as acute icteric hepatitis. This often follows a brief period of flu-like symptoms. Besides liver disease, HEV can affect other areas of the body. It can lead to neurological issues like Guillain-Barré syndrome and neuralgic amyotrophy. It may also cause kidney problems, irregular heartbeats, and blood-related issues. Pregnant women and people with weakened immune systems are at higher risk for severe outcomes. Immune Response and Molecular Insights: The severity of HEV infection depends more on the host's immune response than on direct damage from the virus. Reduced activity of T-cells and NK-cells helps chronic infections persist. Additionally, HEV produces viral microRNAs (miRNAs) that help control viral replication and adjust the host's defense against the virus. Diagnosis: The best way to confirm acute HEV infection is by detecting HEV RNA in blood or stool samples through PCR. Testing for anti-HEV IgM and IgG antibodies can also help with diagnosis, but these methods are less reliable for patients with weakened immune systems. Treatment and Resistance: Most cases of acute HEV infection only need supportive care. For chronic infections, ribavirin is the most effective treatment, achieving a sustained virological response in about 78% of patients. However, mutations associated with resistance, such as Y1320H and G1634R, can reduce treatment effectiveness. Pegylated interferon-α may help some liver transplant recipients, but it poses risks for those with kidney, heart, or lung transplants. Other medications, like sofosbuvir, favipiravir, vidofludimus calcium, and pyrazofurin, are being studied but have shown limited or inconsistent results. Prevention and Control: Preventive steps are key to reducing HEV spread. Better water sanitation and hygiene are crucial for limiting outbreaks. Vaccination also shows promise, with Hecolin® (licensed in China) proving highly effective. However, access to vaccines worldwide is still limited, and challenges remain due to zoonotic reservoirs and the difficulties of multi-dose vaccination schedules.
  • Conclusion: Hepatitis E remains a global health threat, particularly in regions with poor sanitation and among vulnerable groups such as pregnant women and transplant recipients. While most cases are self-limiting, chronic HEV poses challenges in immunocompromised individuals. Current treatments rely heavily on ribavirin, though resistance is an emerging concern. Preventive strategies, especially sanitation improvements and vaccination, are the most effective long-term solutions. Expanding vaccine availability, developing single-dose regimens, and advancing antiviral drug discovery are critical future directions. Overall, a multidisciplinary approach integrating virology, clinical management, and public health measures is essential to control HEV.
  • Keywords: HEV, Prevalence, Transmission, Pathogenesis, Treatment