Hepatitis E virus: epidemiology, molecular mechanisms, clinical manifestations, and emerging therapeutic strategies

Hepatitis E virus (HEV) is a major global health concern, evolving from a self-limited enteric infection to a complex systemic disease with an expanding burden. This narrative review synthesizes current evidence on HEV virology, epidemiology, zoonotic transmission, and clinical manifestations to inform clinicians, researchers, and policymakers. Despite substantial morbidity among pregnant women and immunosuppressed patients, HEV awareness remains limited, and therapeutic options are constrained. Four genotypes (1–4) show distinct epidemiological patterns; chronic infection occurs primarily in immunocompromised hosts, while extrahepatic manifestations, including neurological and renal complications, are increasingly recognized. Treatment remains limited to ribavirin with variable efficacy and contraindications. The HEV-239 vaccine demonstrates sustained efficacy but requires broader implementation. This review integrates recent advances across virology, clinical practice, and public health, offering a unified framework for understanding HEV as a systemic disease requiring enhanced surveillance, targeted antiviral development, and expanded vaccine deployment within a “One Health” framework.