Hepatitis E virus infection and renal injury in non-immunocompromised host: clinical investigation and rabbit model study

Background: Hepatitis E virus (HEV)-associated renal injury is mainly reported in immunocompromised patients. Here, we investigated HEV-associated renal injury in non-immunocompromised acute hepatitis E (AHE) patients and rabbits. Methods: Thirty-five non-immunocompromised AHE patients were tested for kidney function parameters and HEV markers. HEV3- and HEV4-infected rabbits were tested for alanine aminotransferase, creatinine (Cr) and HEV markers. HEV-associated renal injury and renal HEV replication were analyzed by histopathology and RT-qPCR.Results: Non-immunocompromised AHE patients all showed normal serum Cr, Blood Urea Nitrogen (BUN) and urine acid (UA). However, twenty-five percent of non-immunocompromised AHE patients showed proteinuria. In the rabbit model, HEV replication was observed in kidney tissues. HEV-infected rabbits showed transient elevated Cr level. Renal injury, including focal lymphocytic infiltration and tubular protein casts was observed in rabbits across acute, recovery and chronic phases of HEV infection.Conclusions: Proteinuria is not uncommon in non-immunocompromised AHE patients, indicating that HEV infection affects kidney. We further proved that HEV can cause renal injury in a rabbit model.