Disparities in detection of antibodies against hepatitis E virus in US blood donor samples using commercial assays.

Background: Reported hepatitis E virus (HEV) antibody assay performance characteristics are variable. Using a subset of surplus US blood donation samples, we compared assays for detecting anti-HEV immunoglobulin M (Ig)M and IgG or total anti-HEV antibodies.

Study Design And Methods: Samples from 5040 random blood donations, all HEV-RNA negative, collected primarily in the midwestern United States in 2015 were tested for anti-HEV IgM and IgG or total anti-HEV using assays manufactured by Diagnostic Systems, Wantai, and MP Biomedicals.

Results: Overall, the percentage of detection for anti-HEV IgG and total anti-HEV was 11.4%, and for anti-HEV IgM was 1.8%. Nine samples were reactive for anti-HEV IgM by all assays, giving a recent infection rate of 0.18%. Anti-HEV IgG/total anti-HEV detection rates increased with age. Interassay agreement was higher among the IgG anti-HEV/total anti-HEV assays (84%) than the IgM assays (22%). Regression analyses of signal-to-cutoff ratios from IgG/total antibody assay were heteroskedastic, indicating no constant variance among these assays, suggesting they may detect different epitopes or were affected by waning or less avid antibodies in the US donor population.

Conclusions: Although similar percentages of IgG anti-HEV/total anti-HEV detection were observed across the three commercial assays, each assay detected a unique sample subpopulation and was heteroskedastic when compared pairwise. Discordance was higher among anti-HEV IgM assays, but a recent HEV infection rate of at least 0.18% was estimated based on assay concordance.