Two decades of hepatitis E in solid organ transplantation: A retrospective monocentric analysis

BACKGROUND AND AIMS: The awareness regarding hepatitis E virus (HEV) infection in solid organ transplant (SOT) had increased within the last decades after the reports of chronicity and associated complications. The aim of this study was to describe HEV outcome over a long period in a large cohort of SOT patients. APPROACH RESULTS: This retrospective, single-center study analyzed 6452 SOT patients followed between 2001 and 2024 and systematically screened for HEV in cases of elevated liver enzymes. Since 2016, SOT patients were also screened for HEV at 3- and 12-months post-transplantation. We assessed the incidence, natural history, treatment, and extrahepatic manifestations. HEV infection was diagnosed in 228 patients (3.53%). The incidence was significantly higher in liver-transplant patients compared to others. At 3 months post-HEV documentation, 65.1% developed chronic hepatitis, while 34.9% achieved spontaneous viral clearance. Tacrolimus use was independently associated with chronicity, while mycophenolic acid use was protective. Ribavirin was the main antiviral therapy, achieving a 91.5% sustained virological response rate when treatment was extended until complete serum and stool HEV RNA clearance. A minority of patients required multiple treatment courses or failed therapy, with some developing cirrhosis or dying viremic. Three patients died from decompensate HEV-related cirrhosis. HEV-associated neurological manifestations (2.2%) and glomerular diseases (3.9%) were observed, often resolving with viral clearance. CONCLUSION: HEV infection is frequent in SOT recipients, with significant risks of chronicity and extrahepatic complications. Ribavirin remains the cornerstone of treatment, and individualized duration improves outcomes. Screening for HEV is mandatory in SOT patients with elevated liver enzymes.