Performance of Hepatitis E Virus (HEV)-antibody tests: a comparative analysis based on samples from individuals with direct contact to domestic pigs or wild boar in Germany

In Europe, Hepatitis E virus (HEV) genotype 3 causes most human infections, and domestic pigs and wild boar represent the main reservoirs. Contact to these animals represents one source of human infection. However, interpretation of studies is challenged in the absence of a serological gold standard. Hence, this study compared results of different HEV immunoassays. Plasma samples from 139 individuals who had professional contact to pigs (veterinarians, meat inspectors, slaughterhouse workers; n = 114) or hunted regularly (n = 25) were tested with assays specific for HEV IgG, HEV IgM, HEV IgA, and total HEV immunoglobulin as well as for viral RNA. Furthermore, overall HEV IgG was defined (i.e., two of three IgG assays reveal the same result) to compare serological findings. Borderline results were always quoted as positive. For IgG, apparent prevalence was higher in Wantai (48.2%) compared to Euroimmun (11.5%) and Mikrogen assays (17.3%) (p = 0.0001). The overall IgG prevalence was estimated to be 18.7%. For total Ig, Wantai (40.3%) also yielded higher prevalence than Euroimmun (15.8%) (p = 0.0001). The HEV IgM prevalence ranged from 0% (Euroimmun) to 4.3% (Mikrogen). Four percent of individuals tested IgA positive, whilst none harboured HEV RNA. Our results support previous studies that the higher IgG prevalence estimated with the Wantai assay result from a higher sensitivity of this test. However, further studies are needed to verify specificity given the challenge of defining true negative samples. The high percentage of individuals with HEV IgG observed in this study underlines that direct contact to pigs represents a risk factor for HEV infection.