Hepatitis E laboratory tests

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]


Hepatitis E cannot be distinguished from other types of hepatitis based on clinical manifestations alone. Although blood markers of liver injury, such as elevated aminotransferases may be identified, definitive diagnosis of hepatitis E is done by serologic tests. Viral load and antibody titers will vary according to the stage of the infection: during the incubation period, the virus may be detected in blood and in stool; during the clinical manifestation of the disease, ALT and AST are often elevated, the virus may be detected in stool, and anti-HEV IgM and anti-HEV IgG may be detected; during the recovery phase, IgM levels decrease, being detected during 3 to 12 months, while IgG levels may remain detectable throughout many years. Amplification techniques are also useful for detecting HEV infection, viral genotyping, and identifying specific genomic sequences.

Laboratory Findings

Every patient with acute or chronic hepatitis that cannot be explained by other causes, should be tested for hepatitis E.[1] Hepatitis E may be diagnosed by detecting either the HEV nucleic acids, or the antibodies against the virus. Due to the short permanence of the virus in blood and feces, and to the ease of the technique, serologic studies are usually preferred. Unfortunately, the available assays show different specificity and sensitivity, and are only available at certain centers.[2][3] Acute hepatitis E is diagnosed by the detection of anti-HEV IgM against viral antigens, often by enzyme immunoassay.[4]

Throughout the course of infection, serologic markers will vary according to the stage of the disease:[2][3][1]

Laboratory findings
Stage of Infection Findings
Incubation period
Symptom onset
  • Viral clearance
  • Increase of IgG titers (detectable for years to life)
  • Decrease of IgM levels (detectable for 3 to 12 months)
  • HEV detected in stool during the initial period of recovery

The detection of increased levels of anti-HEV IgG may indicate recent HEV infection.[1] Several assays are based on the HEV genotype, therefore, even though the specificity may be high, sensitivity of different tests for the remaining genotypes may be lower.[1]

Immunocompromised patients may have a delayed immune response to HEV, hence delayed seroconversion. For that reason, these patients should be tested for HEV RNA.[5] The RNA of the virus may be detected in blood and stool for several weeks, and if quantified, it may be a marker to evaluate the response to treatment.[1][6]

Enzyme Immunoassays

Enzyme immunoassays are directed to the ORF2 and ORF3 proteins. These tests have low sensitivity and specificity, requiring further improvements.[7]


Amplification techniques are used for the identification of HEV nucleic acids. These techniques also allow:[7]

Amplification techniques may have low sensitivity because when performed, viral load in blood and feces may be low or unidentifiable.[7]


  1. 1.0 1.1 1.2 1.3 1.4 Wedemeyer H, Pischke S, Manns MP (2012). "Pathogenesis and treatment of hepatitis e virus infection". Gastroenterology. 142 (6): 1388–1397.e1. doi:10.1053/j.gastro.2012.02.014. PMID 22537448.
  2. 2.0 2.1 Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
  3. 3.0 3.1 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
  4. Legrand-Abravanel F, Thevenet I, Mansuy JM, Saune K, Vischi F, Peron JM; et al. (2009). "Good performance of immunoglobulin M assays in diagnosing genotype 3 hepatitis E virus infections". Clin Vaccine Immunol. 16 (5): 772–4. doi:10.1128/CVI.00438-08. PMC 2681577. PMID 19321696.
  5. Pischke S, Suneetha PV, Baechlein C, Barg-Hock H, Heim A, Kamar N; et al. (2010). "Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients". Liver Transpl. 16 (1): 74–82. doi:10.1002/lt.21958. PMID 19866448.
  6. Baylis SA, Hanschmann KM, Blümel J, Nübling CM, HEV Collaborative Study Group (2011). "Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance". J Clin Microbiol. 49 (4): 1234–9. doi:10.1128/JCM.02578-10. PMC 3122834. PMID 21307208.
  7. 7.0 7.1 7.2 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.

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