The hepatitis E virus (HEV) is an emergent causative agent of acute hepatitis worldwide, transmitted mainly by the fecal-oral route, which can progress to chronicity in immunosuppressed patients. HEV was first reported in the United States (U.S.) in 1997, but it has been present in the country for an unknown length of time. Despite several studies having examined HEV in the country, neither its prevalence nor its impact is well-understood. Two estimates of HEV seroprevalence from U.S. national studies exposed that HEV infection is not uncommon in the general population, with reported prevalence of 21% and 6% in two periods of time: 1988-1994 and 2009-2016, respectively. In this regard, there appears to be a decline in the seroprevalence over the last 15 years with no concerted interventions directed at the disease. However, it is known that seroprevalence rates may be influenced by the variability of the assay used and by the sampling method with varying number of samples analyzed, studied population, and region of sample origin. Since there is no gold standard technique for HEV antibody detection, it is difficult to perform and accurate determination of the sensitivity or specificity of each test. Interestingly, different analyses of the National Health and Nutrition Examination Survey (NHANES-CDC) have used different HEV tests, raising the question of whether the perceived changes in HEV seroprevalence over time are due to external influences or to test differences.
A recent study led by Dr. Pisano and Dr. Debes provided a meticulous characterization of HEV infection in the United States from 2009 to 2016, examining the prevalence, short-term trends, and potential risk factors for HEV in the U.S. population using data from NHANES-CDC. Additionally, the team examined the differences in HEV seroprevalence from 1988-1994 using 4 different assays, comparing the results with the period 2009-2016 and addressing the agreement between assays.
The estimated HEV seroprevalence between 2009–2016 was 6.1% (95% CI: 5.6%-7.0%) for IgG and 1.02% (0.8%-1.2%) for IgM. Higher HEV IgG prevalence were found in older people, females, non-Hispanic Asians and those born outside of the U.S. They found no significant difference in HEV seroprevalence between different education levels or income groups. Of all other demographic variables addressed, only military status was found to be significant, showing a protective effect.
The in-house immunoassay and the Wantai HEV-IgG ELISA presented the highest sensitivity values in the tested population. The highest specificity values corresponded to the DSI-EIA-ANTI-HEV-IgG assay. The kappa statistical values showed concordances no greater than 0.64 between the assays.
HEV prevalence in their study was similar to previously reported, and a decline in the prevalence was observed through the NHANES assessments (from 1988 to 2016). Non-Hispanic Asians (specific definition by the NHANES data) had a significantly higher average HEV seroprevalence compared to other ethnic groups; the reason for this finding is unclear. Individuals born outside of the U.S. showed a higher HEV seroprevalence, suggesting foreign acquired cases of HEV could be a significant contributor to the overall national seroprevalence in the U.S. Surprisingly, a reduced risk association between military status and HEV infection was noticed. Previous studies indicate otherwise, since military deployment to resource-limited regions has been associated with increased infection risk. It is plausible for a diet-related causation to be considered as protective, as military personnel might adhere to a more restrictive diet. However, this association could be related to chance alone, and should be confirmed by other studies before further speculations.
An issue to be considered for HEV epidemiological analyses, is the wide variability of the tests used to determine seroprevalence rates, which makes comparisons difficult.
Overall, of the evaluated HEV tests during this study, Wantai appeared to have the highest sensitivity, which would make it a potential test for epidemiological studies as previously postulated, and the DS-EIA appeared to have the highest specificity, making it suitable for diagnosis.
In summary, this study shows that the decline in HEV seroprevalence through the NHANES studies (from 1988 to 2016) was real but the wide range of the seroprevalence varied depending on the assay used. The variation in the kits for determination of HEV serology highlights a need to develop a gold standard assay or to standardize existing assays when conducting nationwide seroepidemiologic surveys.
Read the full article (PLoS One. 2022 Aug 5;17(8):e0272809): DOI: 10.1371/journal.pone.0272809
