Hepatitis E virus infection in kidney transplant recipients: a pilot cross-sectional study of serological markers and allograft function in Northern Serbia.

Background: Hepatitis E virus (HEV) is an emerging cause of chronic hepatitis and extrahepatic disease in solid organ transplant recipients. Data on kidney transplant populations, particularly in endemic regions, remain limited. This pilot study aimed to quantify the prevalence of HEV exposure and active infection in kidney transplant recipients and examine associations between HEV markers and allograft function. Methods: In this single-centre cross-sectional pilot study, 25 adult kidney transplant recipients (mean age 48.9 ± 14.4 years, median 13.0 years post-transplant) with available HEV serology and/or RNA testing were included. Clinical data, liver enzymes, estimated glomerular filtration rate (eGFR, mL/min/1.73 m²), and urinary albumin-to-creatinine ratio were obtained from medical records; allograft function was categorised as better versus worsening based on longitudinal clinical and laboratory trends documented in medical records. HEV exposure and active infection were assessed using anti-HEV IgG and IgM antibodies (Euroimmun ELISA; reactive ≥ 1.1, borderline 0.8-1.1, negative < 0.8) and HEV RNA in serum and stool. Results: Anti-HEV antibodies were present in 19/25 (76%) patients; HEV RNA was detected in 2/25 (8%) patients, with concurrent serum and stool positivity confirmed in both cases. eGFR data were available in 15 patients (60%). IgG serostatus was not associated with eGFR differences, but IgM-positive recipients had significantly lower eGFR (median 35.5 vs 57.5 mL/min/1.73 m²; p = 0.018; Cliff's δ = 0.74) and higher liver enzyme activity. In an exploratory regression model (n = 15), anti-HEV IgM positivity was associated with approximately 29.8 mL/min/1.73 m² lower eGFR (R² = 0.50), though this estimate is hypothesis-generating given the small sample. Anti-HEV IgM was the strongest individual predictor of worsening graft function (OR = 3.00; 95% CI 0.37-24.5). Conclusions: In this endemic setting, kidney transplant recipients showed high HEV seroprevalence and an exploratory association between IgM positivity and impaired allograft function. These hypothesis-generating findings support targeted HEV evaluation-including RNA testing-in kidney transplant recipients with unexplained graft dysfunction or mild transaminase elevation in an endemic South-Eastern European setting. Larger longitudinal studies with kidney biopsies are needed to define the renal impact of HEV and determine whether anti-HEV IgM may serve as a risk-stratification marker.