Serologic Markers for Hepatitis E Infection Diagnosis

laboratory assistant analyzing a blood sample
The persistence of hepatitis E virus (HEV) markers after acute self-limited hepatitis E was assessed and according to the data published in Journal of Viral Hepatitis, the serologic test HEV-Ag performed best overall.

The persistence of hepatitis E virus (HEV) markers after acute self-limited hepatitis E was assessed and according to the data published in Journal of Viral Hepatitis, the serologic HEV-Ag test performed best overall. It had a positive predictive value of 100% and diagnostic accuracy of 57%, however, anti-HEV immunoglobulin (Ig) M had unexpectedly long persistence.

To investigate the persistence of HEV markers investigators carried out HEV serologic tests (IgM by Mikrogen and Wantai and HEV-antigen [Ag]) and HEV RNA in 2 cohorts. One included patients with prior acute hepatitis E (alanine transaminase >10-times the upper limit of normal plus positive IgM ± HEV RNA) currently self-limiting, and the other comprised of 50 blood donors with positive HEV RNA. A cohort of 25 patients with a history of HEV were retested between 2 and 4 years post-acute infection.

During a median follow-up of 34 months, all of the 25 patients who had a prior case of acute hepatitis E demonstrated undetectable HEV RNA. Anti-HEV IgM did remain detectable though in 56% by Mikrogen, 24% by Wantai and none for HEV-Ag. Within the second year, anti-HEV IgM was positive in 80% to 100% of patients, and 17% to 42% over 3 years later, by Wantai and Mikrogen respectively. In the cohort of HEV RNA positive donors 25% tested positive for either IgM by Mikrogen or Wantai, 18% for both and 36% for HEV-Ag. Also, when HEV RNA was higher, HEV-Ag positivity was more likely (14% if <2.2 log IU/mL; 64% if RNA ≥ 3.7 log IU/mL).

The investigators highlighted that overall, the test with the best performance was HEV-Ag, a positive predictive value of 100% and negative predictive value of 44%, resulting in a diagnostic accuracy value of 57%. This accuracy is higher than the 42% and 31% obtained with the Wantai and Mikrogen anti-HEV IgM assays, respectively.

Investigators noted several study limitations including, diagnosis of acute hepatitis E being based on IgM positivity, with not all cases testing for HEV RNA. They also noted that a limited number of patients were included in the study. The main advantage, though, was that all patients with acute hepatitis E met the classic criteria for acute hepatitis with transaminases levels > 10-fold of the upper limit of normal and the minimum criterion for acute hepatitis E diagnosis according to the European Centre for Disease Prevention and Control.

The results provided, “previously unreported information on the long duration of anti HEV IgM assays after self-limited acute hepatitis E.” Investigators concluded that in self-limited acute hepatitis E, the persistence of anti-HEV IgM differed depending on the assay used. Comparisons of patients with transient HEV RNA blood donors and self-limited HEV infection found that HEV-Ag showed better performance than the anti-HEV IgM assay, as it had a positive predictive value of 100%. Therefore, according to the investigators, “it can be considered a useful tool for diagnosing acute HEV infection in settings where HEV RNA is not available.”

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Riveiro-Barciela M, Rando-Segura A, Barreira-Díaz A, et al. Unexpected long-lasting anti-HEV IgM positivity: Is HEV antigen a better serological marker for hepatitis E infection diagnosis? [published online February 27 2020]. J Viral Hepat. doi:10.1111/jvh.13285