Hepatitis E virus has, over the past few years, been increasingly recognised as a cause of acute hepatitis in the western world. The first hepatitis E Standard for Microbiology Investigations (SMI) was issued in November 2018 and recommends cascading testing in immunocompetent individuals, with RNA assays clarifying results of antibody assays. We investigated all clinical samples tested for hepatitis E in our regional laboratory between October 2014 and October 2018 (12671 IgM, 10738 IgG and 2290 RNA assays). In 495 cases, samples collected within 24 hours from a patient underwent IgM assays (DS2 platform) and PCR assays (in-house). 7 pairs, corresponding to 5 patients, of 404 pairs with negative or low-positive IgM results, had detectable RNA. 4 of those 5 patients were demonstrably immunocompromised; the final sample came from general practice without further details. 3/5 patients had reactive IgG assays, and one of the two remaining patients had a rise in IgM titre between two successive samples. We conclude that, in our sample population, hepatitis E RNA PCR testing adds minimal diagnostic information in immunocompetent individuals with negative or low-positive IgM results. This finding supports current testing cascade recommendations. We discuss our sample population’s demographics and external validity of findings: in particular, we saw few tests sent by neurologists. Finally, we briefly discuss other IgM/IgG/PCR result scenarios and our findings in relation to current SMI recommendations, and speculate how our findings affect understanding of antibody response and viraemia in hepatitis E infection.

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