Performance of anti-HEV assays for diagnosing acute hepatitis E in immunocompromised patients

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Abstract

Hepatitis E virus is an emerging concern in immunocompromised patients, who may become chronically infected. This prompted us to assess the performance of two anti-HEV IgG and IgM assays for diagnosing acute HEV infections. The specificities of the assays were estimated by testing samples from 2 to 3 year-old French children and blood donors and their sensitivities by testing 40 immunocompromised patients acutely infected. Both anti-HEV IgM assays were highly specific (99.6% and 100%). The sensitivity of the Adaltis was 87.5%, and that of Wantai was 85%. The specificities of anti-HEV IgG Wantai (97.8%) and Adaltis tests (89.5%, p = 0.1) were similar but the Wantai test was more sensitive (45%) than the Adaltis test (15%, p < 0.001). None of the samples was anti-HEV IgM negative and IgG positive. We conclude that these anti-HEV IgM assays performed well in immunosuppressed subjects with acute hepatitis E and can be used as first line virological tools. Testing for anti-HEV IgG and IgM simultaneously at the acute phase did not improve the diagnostic performance. In contrast, molecular detection of HEV RNA appears essential to exclude an HEV infection in patients who are negative for anti-HEV IgM and to assess the evolution of hepatitis E 3 months thereafter.

Section snippets

Background

The hepatitis E virus (HEV) has been recognized for decades as a major cause of outbreaks associated with faecal contamination of drinking water in developing countries. This pathogen is now also recognized as a major etiologic agent of acute hepatitis in industrialized countries that is transmitted zoonotically [1], [2].

HEV is an RNA virus with a single-stranded, positive sense approximately 7.2 kb genome containing partially overlapping open reading frames (ORFs). ORF1 encodes a nonstructural

Objectives

We have assessed the performance of two commercially available anti-HEV IgM and IgG tests, the Adaltis and the Wantai tests, the main serological assays employed in Europe, for diagnosing acute HEV infections in immunosuppressed patients.

Serum samples

All samples were collected in France. The specificities of the anti-HEV IgM assays were assessed by testing samples from 233 HEV-negative blood donors (HEV RNA negative, anti-HEV IgG negative with the HEV IgG ELISA kit; Wantai). Those of the anti-HEV IgG assays were assessed by testing samples from 180 2–3 year-old children hospitalized for surgery or trauma. The sensitivities of the HEV serological assays were determined using sera collected from 40 HEV immunocompromised patients whose sera

Performance of the anti-HEV IgM tests

Specificity was determined by testing 233 anti-HEV IgG and HEV RNA negative samples. The Wantai ELISA for HEV IgM found that 232 of them were negative (specificity: 99.6%, 95% confidence interval (95%CI): 98.7–100%), while the Adaltis EIAgen HEV IgM kit found that all 233 samples were negative (specificity: 100%, 95%CI: 99.8–100, p = 0.49) (Table 1).

We have assessed the sensitivity of the anti-HEV IgM tests by testing 2 panels of patients. The mean HEV RNA concentrations was 5.6 ± 1.1 log copies/ml

Discussion

We have evaluated the performance of two commercial anti-HEV IgG and IgM assays in immunocompromised patients during the acute phase. Both anti-HEV IgM assays were highly specific and sensitive (87.5% and 85%). The specificities of the anti-HEV IgG assays were similar but they were rather insensitive and did not contribute to the diagnosis of acute hepatitis E.

The presence of anti-HEV IgM is a marker of acute infection. A recent study evaluated the performance of six IgM anti-HEV enzyme

Funding

The National Reference Centre for Hepatitis E is supported by a grant from the French Public Health Authorities.

Competing interests

The authors declared no conflict of interest with respect to this manuscript.

Ethical approval

Not required.

Acknowledgements

We thank Delphine Gregoire and Sylvie Beaubatie for technical support. The English text was checked by Dr. Owen Parkes.

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