Variability in the performance characteristics of IgG anti‐HEV assays and its impact on reliability of seroprevalence rates of hepatitis E

Abstract

Hepatitis E is a major public health problem in developing countries and is increasingly being recognized as a cause of substantial sporadic viral hepatitis infections in industrialized countries. Variable rates of hepatitis E seroprevalence have been reported from the same geographic regions depending on the assay used. In this study, we evaluated the performance characteristics of four assays which included two commercial assays, Wantai HEV-IgG ELISA kit (Wantai, China), and DS-EIA-ANTI-HEV-G kit (DSI, Italy), one NIH-developed immunoassay (NIH-55 K, Kuniholm et al. [2009] Journal of Infectious Diseases 200:48-56), previously used in several major seroprevalence studies and one in-house Western blot assay (CDC-WB). The limit of detection of IgG anti-HEV is 100 mIU/mL for Wantai assay, 200 mIU/mL for CDC-WB assay, 1000 mIU/mL for DSI assay, and 40 mIU/mL for NIH-55 K assay. Pairwise concordance between the four assays ranged from 56% to 87%. The concordance among all four assays was observed in 52% of the samples, while the concordance among three assays was observed in 37% of the samples. These data show a wide discordance between various IgG anti-HEV assays and warrant a comprehensive evaluation of all the assays using well characterized global serum reference panels.

Seroprevalence and incidence of hepatitis E virus among blood donors: A review

“…Based on several studies performed to estimate HEV seroprevalence, like those conducted in some European countries (Table ), it was noted that 3 different studies performed at almost the same time revealed wide variation in HEV seroprevalence (Table ). Furthermore, studies that were performed on acute hepatitis samples revealed variation in the diagnostic performance characteristics of anti‐HEV IgM commercial assays . In conclusion, as shown in Table , seroprevalence of HEV is not only affected by the sample size and the geographic distribution of HEV, but also by the type of immunoassay used.…”

“…In conclusion, as shown in Table , seroprevalence of HEV is not only affected by the sample size and the geographic distribution of HEV, but also by the type of immunoassay used. Hence, discrepancies in the diagnostic performance characteristics of HEV assays can greatly affect the apparent seroprevalence of HEV …”

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

“…Part of the problem is that clinical assays are validated to determine the status of an analyte in a symptomatic individual and not specifically for epidemiologic studies of healthy populations. This is particularly true of HEV serological assays because the lack of concordance has led to variable findings in asymptomatic populations when commercial assays have been compared . Currently, there are no Food and Drug Administration–approved anti‐HEV or HEV‐RNA assays.…”

Probable transmission of hepatitis E virus (HEV) via transfusion in the United States

“…A study by Kuniholm et al, of 18,695 individuals from the Third National Health and Nutrition Examination Survey (NHANES) that represents the 1988–1994 US population, found an IgG anti‐HEV prevalence of 21% by using an assay that was developed at NIH . Another study, using an ELISA that has been reportedly less analytically sensitive than the Wantai HEV‐IgG ELISA (that we used) and the NIH‐developed assay, determined a decline in IgG anti‐HEV prevalence from that in the 1998–1994 NHANES population (10% weighted, 17% unweighted) to that in the 2005–2006 NHANES population (6%, weighted or unweighted) . Regardless of diminishing IgG anti‐HEV prevalence, which others have recognized, these reports have provided persuasive evidence that HEV infections, which often are subclinical, are common in the United States.…”