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

Abstract

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: A total of 35 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: The non-immunocompromised AHE patients all showed normal serum Cr, blood urea nitrogen (BUN), and urine acid (UA). However, 25% of non-immunocompromised AHE patients showed proteinuria. In the rabbit model, HEV replication was observed in kidney tissues. The HEV-infected rabbits showed a 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 the kidney. We further proved that HEV can cause renal injury in a rabbit model.