Background Hepatitis E virus (HEV) infection in immunocompromised patients such as solid organ transplant recipients may bear a high risk of becoming a chronic infection with progression to liver cirrhosis. So far, data onHEVinfection in pediatric renal transplant recipients are limited. Methods This single-center cohort study investigated period prevalence, morbidity, and treatment of HEV infection in 90 pediatric renal allograft recipients aged 9.9 +/- 5.6 years at transplantation (58.9% males). HEV serology was determined by enzyme-linked immunosorbent assay and immunoblot, HEV replication by quantitative nucleic acid testing. Results Twelve of 90 (13.3%) patients were HEV seropositive, and 4/90 (4.4%) recipients showed active HEVreplication (103108 copies/mL, corresponding to 0.5 x 103 and 0.5 x 108 WHO IU/mL) in serum and stool. In all patients with HEV replication, genotype 3 was identified by partial sequencing of HEV ORF1 and ORF2 and phylogenetic analysis. All patients with HEV replication developed chronic infection associated with moderately elevated liver enzymes. HEVreplication was unresponsive to reduction of immunosuppression, whereas ribavirin monotherapy (mean dosage 9.7 +/- 3.6 mg/kg per day over 85 +/- 11 days) was associated with sustained viral clearance and normalization of liver enzymes in all patients. Ribavirin therapy was associated with reversible, hyporegenerative anemia. Conclusions Given an HEV seroprevalence of 13.3% in pediatric renal transplant recipients and an HEV viremia of 4.4%, HEV infection should be considered in patients with otherwise unexplained elevation of liver enzymes. HEV infection does not necessarily respond to reduction of immunosuppressive therapy, but can be effectively and safely treated with ribavirin.