Diagnostic performance of hepatitis E virus antigen assay in hepatitis E virus acute infection

The aim of this study was to analyze the sensitivity of hepatitis E virus antigen (HEV-Ag) to determine acute E hepatitis. Ninety-four serum samples resulting anti-HEV IgM by DIA.PRO assay were analyzed with Wantai assay to check for HEV-Ag. Thirty samples were anti-HEV IgM positive and HEV-RNA positive, 19 samples harbored genotype 3, whereas 11 samples were genotype 1. Overall, 16% of anti-HEV IgM samples resulted HEV-Ag positive and 33.3% of HEV-RNA positive were also HEV-Ag positive. Among 64 HEV-RNA negative samples, 5 (7.8%) were HEV-Ag positive. The concordance of HEV-RNA and HEV-Ag was low (Cohen's Kappa=0.36). The Bland-Altman plot revealed a low agreement between HEV-RNA viral load and HEV-Ag, confirmed by a not significant Spearman's correlation coefficient (rho=0.137, p>0.05). Moreover, the HEV-Ag showed 100% specificity. In genotype 3f samples with a viral load >800 cp/ml HEV-Ag was positive in 80% of samples, whereas all patients harboring genotype 3e were HEV-Ag-negative irrespective of HEV-RNA viral load. Among genotype 1, HEV-Ag positivity was observed only in 27.7% patients and in all samples the viremia was >2000 cp/ml. These data suggest that anti-HEV IgM positivity represents the main biological marker of hepatitis E acute infection in clinical real life settings in developed countries.