Interferon‑λ4 gene polymorphisms, circulating interferon λ3, and clinical variables in hemodialysis patients exposed to hepatitis E virus

Introduction Factors associated with hepatitis E virus (HEV) infection are rarely recognized in patients on renal replacement therapy (RRT), and the results of studies are inconsistent.
Objectives We aimed to search for determinants of HEV seroprevalence among polymorphisms of the interferon‑λ4 gene (IFNL4) associated with seroclearance of hepatotropic viruses (IFNL4 rs12979860, rs8099917 near IFNL4), circulating interferon λ3 (IFN‑λ3), and clinical variables of patients treated with hemodialysis (HD) in a HEV‑endemic region.
Patients and methods The study was carried out in 90 HD patients. HEV open reading frame 2 antigen (HEV Ag), immunoglobulin M and G antibodies to HEV (anti‑HEV IgM and anti‑HEV IgG, respectively) and IFN‑λ3 were tested, and IFNL4 polymorphic variants (rs8099917, rs12979860) were genotyped. Survival analysis was conducted concerning anti‑HEV IgG positivity.
Results In the study group, there were 37.8% anti‑HEV IgG‑positive subjects. None was HEV Ag or anti‑HEV IgM positive. HD modalities utilizing high‑flux dialyzers (adjusted odds ratio [OR], 3.586; 95% confidence interval [CI], 1.142–11.263; P = 0.03) as well as major homozygosity in rs8099917 (adjusted OR, 4.933; 95% CI, 1.516–16.054; P = 0.008) and rs12979860 (adjusted OR, 3.537; 95% CI, 1.136–11.014, P = 0.03), but not circulating IFN‑λ3 levels, were positive determinants of anti‑HEV IgG positivity. Liver enzyme activities and C‑reactive protein levels tested as response variables to HEV exposure, as well as survival probability, were not different between patients stratified by anti‑HEV IgG positivity.
Conclusions Among HD patients, IFNL4 polymorphisms and treatment with high‑flux HD are explanatory variables for isolated anti‑HEV IgG positivity indicating spontaneous HEV resolution.