Maad Rayan Publishing Company Biomedical Research Bulletin 2980-9924 3 3 2025 09 29 Hepatitis E Virus: Understanding Transmission, Zoonotic Impacts, and Global Health Challenges 146 148 10.34172/biomedrb.9089 EN Amir Mohammad Naghshe Javaheri https://orcid.org/0009-0003-1754-2156 Mohammadreza Ghorani https://orcid.org/0000-0001-7066-0344 Mahdiye Shirafkan Ali Mosayyebzadeh Hannaneh Besharat Damirchi REVIEW 10.34172/biomedrb.9089 2025 07 28 2025 09 03 The hepatitis E virus (HEV) is a global health issue, particularly in regions where it is endemic, accounting for over half of all acute viral hepatitis cases. HEV is zoonotic, with animals such as swine, rabbits, deer, and rodents serving as reservoirs. This virus is primarily transmitted via the fecal-oral route through contaminated water and food, leading to outbreaks in areas with poor sanitation. Human-to-human transmission is rare, but other routes, including blood transfusions and vertical transmission from mother to fetus, are increasingly recognized, contributing to high stillbirth rates in developing countries. Moreover, HEV infections vary from asymptomatic to severe, potentially resulting in fatal fulminant hepatic failure. Immunocompromised individuals, such as organ transplant recipients, are at heightened risk of persistent infections that can progress to cirrhosis. Diagnosis relies on molecular methods (PCR) and serological assays (ELISA) for detecting HEV RNA and identifying anti-HEV antibodies, respectively. Birds, rabbits, and bats serve as reservoirs. Human HEV cases are mainly linked to genotypes 3 and 4, with primary reservoirs being domestic swine, wild boar, and deer. In addition, transmission can occur through direct animal contact, environmental contamination, organ transplants, and blood transfusions. Preventive measures focus on improving sanitation in developing regions while avoiding raw or undercooked animal products in developed countries. Studies demonstrate varying HEV seroprevalence among animals across different regions, highlighting the importance of understanding specific risk factors for transmission. Overall, HEV is a serious global health threat, with effective control and prevention requiring sustained research, improved sanitation, and comprehensive surveillance efforts.