Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients

Abstract

Background: Hepatitis E virus (HEV) genotype 3 is recognised as an emerging pathogen in industrialised countries. The currently commercially available HEV-specific enzyme linked immunosorbent assays (ELISAs) are primarily designed for the detection of antibodies against genotypes 1 (Burma) and 2 (Mexico) and may not sensitively detect HEV genotypes 3 or 4.

Objectives: This study aimed to evaluate the analytical and clinical performances of eight commercially available HEV serum antibody immunoglobulin M (IgM)- and immunoglobulin G (IgG)-specific ELISAs for genotype 1 and 3 HEV infections in a clinical setting and to study the antibody responses against HEV of immunocompromised versus immunocompetent patient groups.

Study design: Analytical performance and diagnostic sensitivity and specificity were assessed using well-defined reference samples and samples from patients with polymerase chain reaction (PCR)-confirmed HEV infection (n=88) and a specificity panel (n=98).

Results: Limiting dilutions indicated that the highest analytical sensitivity in head-to-head comparison was measured for the Mikrogen_new IgG assay. Taking the serum working dilutions of each assay into account, the Wantai IgG assay was the most sensitive assay. Receiver operator curve (ROC) analysis showed area under the curve (AUC) values of 0.943, 0.964, 0.969, 0.971, 0.974 and 0.994 for the DSI, Mikrogen_old, MP Diagnostics, Mikrogen_new, Wantai and DiaPro anti-HEV IgM assays, respectively. The highest specificity of currently available assays was found for the IgM Wantai assay (>99%). If anti-HEV IgM and IgG results from each supplier were combined, DSI and Wantai assays were able to detect the highest number of (passed) HEV infections.

Conclusions: Our study showed that current commercial HEV ELISAs could be used to diagnose HEV genotype 3 infection adequately in a clinical setting.

Keywords: AUC; CMV; Diagnostics; EBV; ELISA; Epstein–Barr virus; HAV; HBV; HCV; HEV; Hepatitis E virus; Immune response; Immunocompromised; LIMS; OD; ORF; RNA; ROC; RT-PCR; S/N; Transplantation; WHO; World Health Organization; area under the curve; cytomegalovirus; enzyme linked immunosorbent assay; hepatitis A virus; hepatitis B virus; hepatitis C virus; hepatitis E virus; laboratory information management system; open reading frame; optical density; receiver operator curve; reverse transcriptase polymerase chain reaction; ribonucleic acid; signal to noise.