Hepatitis E virus and renal injury: A review of pathogenesis, pathology, and clinical management

Hepatitis E virus (HEV), particularly Orthohepevirus A genotypes 1–4, is a major cause of acute viral hepatitis, with genotypes 3 and 4 also recognized as important zoonotic pathogens and increasingly associated with extrahepatic renal manifestations, which have emerged as a critical clinical challenge. Despite the growing body of case reports, a comprehensive synthesis of the biological mechanisms and standardized management for HEV-related kidney disease is still lacking. Biologically, HEV demonstrates distinct renal tropism, capable of completing its replication cycle within renal tubular epithelial cells and excreting infectious virions via urine. This review systematically explores the relationship between HEV and renal impairment, detailing the diverse renal pathologies ranging from acute kidney injury to immune-complex–mediated glomerulonephritis, such as IgA nephropathy, which manifests with greater frequency and severity in immunocompromised individuals. The underlying mechanisms are multifaceted, primarily involving the deposition of immune complexes containing the HEV open reading frame 2 capsid protein and host antibodies, which activate complement and drive glomerular injury, as well as potential direct cytopathic effects. Consequently, this article summarizes current clinical management, centering on antiviral therapy with ribavirin and the careful modulation of immunosuppressive regimens to provide a theoretical framework for clinicians.