Hepatitis E Virus in immunosuppressed patients in the era of global mobility

Hepatitis E virus (HEV) has emerged as a major, yet under-recognized, public health challenge worldwide, particularly in the context of increasing global mobility and expanding populations of immunosuppressed individuals. Zoonotic HEV, now the leading cause of acute viral hepatitis in Europe, is hindered by markedly heterogeneous surveillance systems, diagnostic strategies, and preventive policies, which limit cross-country comparability obscuring the true disease burden. Underdiagnosis is compounded by the existence of extrahepatic manifestations that escape conventional hepatotropic case definitions. At the same time, chronic HEV infection has gained clinical relevance among immunocompromised hosts, including solid organ transplant recipients, patients with hematologic malignancies, and those receiving biologic or other immunomodulatory therapies. However, the mechanisms driving viral persistence, progression to chronicity, and optimal antiviral management remain incompletely defined. This review synthesizes current epidemiological, clinical, and virological knowledge on HEV in Europe, with a focus on the implications of global migration, and the growing population at risk due to immunosuppression. It highlights key gaps and priority areas, particularly the management of infection in immunocompromised hosts and the development and implementation of targeted vaccination strategies for high-risk groups. In conclusion, integrated cross-disciplinary action is needed in response to this emerging threat.