SAGE IVD recommended including the hepatitis E virus IgM ELISA antibody test category in EDL 4
• as a disease-specific IVD for use in clinical laboratories (EDL 4, Section II.b);
• using an immunoassay format;
• using serum and plasma as specimen types;
• to diagnose acute hepatitis E virus infection.

Hepatitis E is an acute viral hepatitis caused by HEV infection. Most affected people recover. However, a small proportion – generally less than 5% but much higher in pregnant women – develop acute liver failure. Hepatitis E should always be considered in outbreaks of acute jaundice syndrome, which have occurred more recently across sub-Saharan Africa, and particularly in the context of internally displaced person camps. Definitive diagnosis of hepatitis E is challenging, as causes of acute jaundice are many and include yellow fever, hepatitis A and leptospirosis. For countries experiencing outbreaks, the problem of differential diagnosis is exacerbated by lack of access to hepatitis E assays. The HEV IgM ELISA is one of three hepatitis E assays submitted as new additions to EDL 4. ELISA is well established in many laboratories and settings. SAGE IVD members questioned whether all three assays are needed and noted uncertainties about how best to use the laboratory-based and RDT tests for diagnosing HEV infection. One SAGE IVD member noted that RDT and NAT and ELISA are all essential for a laboratory network and how individual countries choose to implement the tests will be decided on the ground. Moreover, WHO is currently updating its guidance, which includes generating a consolidated algorithm for HEV assays. One SAGE IVD member also raised a concern that the evidence submitted is at higher risk of bias owing to the nature of the populations studied. However, it was pointed out that better studies are unlikely to be done in the near future. Literature cited in the discussion: European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection. J Hepatol. 2018;68:1256–71 (https://www.journal- of-hepatology.eu/article/S0168-8278(18)30155-7/fulltext, accessed 14 December 2022).

Hepatitis E infection is a significant global health problem. IgM EIAs for diagnosing HEV infection are included in the WHO guidance (11, 15). The 2018 EASL guidelines also recommend a combination of anti-HEV-IgM and nucleic acid testing for HEV infection (10.1186/S12884-020-03116-2). Evidence to assess clinical utility/effectiveness is insufficient. The diagnostic accuracy estimates presented for this application are probably too optimistic, as case–control designs were used in the studies. If diagnostic accuracy were suboptimal, the value of the test would depend on how it would be used in conjunction with other tests in the diagnostic pathway. More studies are needed that evaluate the test in the intended use population. In the absence of such evidence, other factors may weigh more heavily in eventually deciding to use this test, such as resources required, acceptability and equity.

World Health Organization. (‎2023)‎. The selection and use of essential in vitro diagnostics: report of the fourth meeting of the WHO Strategic Advisory Group of Experts on In Vitro Diagnostics, 2022 (‎including the fourth WHO model list of essential in vitro diagnostics)‎. World Health Organization. https://iris.who.int/handle/10665/373322