Hepatitis E (HEV)

Testing for HEV infection in immunocompromised patients

Diagnostic HEV markers and disease stages

ALT	normal
anti-HEV IgM	-
anti-HEV IgG	-
HEV RNA	(+)
Symptoms	-

(…) = potentially present

ALT	(elevated)
anti-HEV IgM	(+)
anti-HEV IgG	(+)
HEV RNA	+
Symptoms	(+)

(…) = potentially present

ALT	elevated
anti-HEV IgM	(+)
anti-HEV IgG	(+, rising)
HEV RNA	+
Symptoms	+

(…) = potentially present

ALT	(elevated)
anti-HEV IgM	-
anti-HEV IgG	(+)
HEV RNA	+
Symptoms	(+)

(…) = potentially present

Adapted from:

Abravanel F, et al. Diagnostic and management strategies for chronic hepatitis E infection, Exp Rev Anti-inf Ther. 2023;21:143-148.
Aggarwal R and Goel A. Natural History, Clinical Manifestations, and Pathogenesis of Hepatitis E Virus Genotype 1 and 2 Infections. Cold Spring Harb Perspect Med. 2019;9(7):a032136.
Webb GW and Dalton HR. Hepatitis E: an underestimated emerging threat. Ther Adv Infect Dis. 2019;6:1-18.
Lhomme S, et al. Screening, diagnosis and risks associated with Hepatitis E virus infection. Exp Rev Anti-inf Ther. 2019;17:403-418.
Kamar, N., Izopet, J., Pavio, N. et al. Hepatitis E virus infection. Nat Rev Dis Primers; 2017;3, 17086.

Product	Description	Tests
Elecsys^® Anti-HEV IgM ^a)	Electrochemiluminescence immunoassay (ECLIA) for the qualitative detection of IgM antibodies to the hepatitis E virus (HEV) in human serum and plasma	100
Elecsys^® Anti-HEV IgM ^b)		300
Elecsys^® Anti-HEV IgG ^a)	Electrochemiluminescence immunoassay (ECLIA) for the quantitative determination of IgG antibodies to the hepatitis E virus (HEV) in human serum and plasma	100
Elecsys^® Anti-HEV IgG ^b)		300
cobas^® HEV ^c)	Qualitative in vitro nucleic acid amplification test for the direct detection of HEV RNA (genotypes 1-4) in human plasma	96

a) for use on the cobas^® e 411 analyzer and the cobas^® e 601 / 602 modules;
b) for use on the cobas^® e 402 and cobas^® e 801 analytical units
c) intended for use to screen donor samples for HEV RNA in plasma samples from individual human donors, including donors of whole blood, blood components (red cells, platelets, and plasma), and other living donors; not intended for use as an aid in diagnosis for HEV; for use on the cobas^® 6800/8800 Systems

Adapted from:

Abravanel F, et al. Diagnostic and management strategies for chronic hepatitis E infection, Exp Rev Anti-inf Ther. 2023;21:143-148.
Kar, P, Karna R. A Review of the Diagnosis and Management of Hepatitis E. Curr Treat Options Infect Dis. 2020;12:310–320.
Aslan AT, Balaban HY. Hepatitis E virus: Epidemiology, diagnosis, clinical manifestations, and treatment. World J Gastroenterol. 2020;26:5543-5560.
Public Health England. Public health operational guidelines for hepatitis E. Health protection response to reports of hepatitis E infection. 2019 Guidelines. Internet [updated 2019 Sep; cited 2023 May]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/845090/Public_Health_Operational_Guidelines_for_Hepatitis_E-protection_response.pdf.
Lhomme S, et al. Screening, diagnosis and risks associated with Hepatitis E virus infection. Exp Rev Anti-inf Ther. 2019;17:403-418.
European Association for the Study of the Liver (EASL). Clinical Practice Guidelines on hepatitis E virus infection. J Hepatol 2018;68:1256-1271.
Murali AR, et al. Chronic hepatitis E: A brief review. World J Hepatol. 2015;7:2194-201.

Step 1
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Step 3

Step 1

Perform HEV RNA, anti-HEV IgM, and anti-HEV IgG in parallel

HEV RNA

anti-HEV IgM

anti-HEV IgG

Step 1
Step 2
Step 3

Step 2

Monitor HEV RNA levels for up to 3 months.

HEV RNA remains detectable

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Step 2
Step 3

Step 2

Monitor HEV RNA levels for up to 3 months.

HEV RNA remains detectable

Step 1
Step 2
Step 3

Step 2

Monitor HEV RNA levels for up to 3 months.

HEV RNA remains detectable

Step 1
Step 2
Step 3

Step 2

Monitor HEV RNA levels for up to 3 months.

HEV RNA remains detectable

Step 1
Step 2

Summary

No evidence of HEV infection.

Step 1
Step 2

Summary

Past HEV infection.

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Step 2

Summary

Recent acute HEV infection.

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Step 2

Summary

No evidence of HEV infection

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Step 2

Summary

Implausible result.

Possible false positive anti-HEV IgM.

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Step 3

Summary

Cleared HEV infection.

Step 1
Step 2
Step 3

Summary

Chronic HEV infection
For management of patients with chronic hepatitis E, refer to clinical practice guidelines.

Step 1
Step 2
Step 3

Summary

Cleared HEV infection.

Step 1
Step 2
Step 3

Summary

Chronic HEV infection
Continue with monthly HEV RNA monitoring.

For management of patients with chronic hepatitis E, refer to clinical practice guidelines.

Step 1
Step 2
Step 3

Summary

Cleared HEV infection.

Step 1
Step 2
Step 3

Summary

Chronic HEV infection
Continue with monthly HEV RNA monitoring.

For management of patients with chronic hepatitis E, refer to clinical practice guidelines.

Step 1
Step 2
Step 3

Summary

Cleared HEV infection.

Step 1
Step 2
Step 3

Summary

Chronic HEV infection
For management of patients with chronic hepatitis E, refer to clinical practice guidelines.

Back

Step

Result

Interpretation

HEV RNA test = ...
anti-HEV IgM test = ...
anti-HEV IgG test = ...

waiting for input

HEV RNA test = positive
anti-HEV IgM test = positive
anti-HEV IgG test = positive

Compatible with HEV infection
Monitor HEV RNA levels for up to 3 months.

HEV RNA test = positive
anti-HEV IgM test = positive
anti-HEV IgG test = negative

Compatible with HEV infection.
Monitor HEV RNA levels for up to 3 months.

HEV RNA test = positive
anti-HEV IgM test = negative
anti-HEV IgG test = positive

Compatible with HEV infection
Monitor HEV RNA levels for up to 3 months.

HEV RNA test = positive
anti-HEV IgM test = negative
anti-HEV IgG test = negative

Compatible with HEV infection
Monitor HEV RNA levels for up to 3 months.

HEV RNA test = negative
anti-HEV IgM test = positive
anti-HEV IgG test = positive

Recent acute HEV infection.

HEV RNA test = negative
anti-HEV IgM test = positive
anti-HEV IgG test = negative

Implausible result.

HEV RNA test = negative
anti-HEV IgM test = negative
anti-HEV IgG test = positive

Past HEV infection

HEV RNA test = negative
anti-HEV IgM test = negative
anti-HEV IgG test = negative

No evidence of HEV infection.

HEV RNA test = ...
anti-HEV IgM test = positive
anti-HEV IgG test = ...

waiting for input

HEV RNA test = ...
anti-HEV IgM test = negative
anti-HEV IgG test = ...

waiting for input

HEV RNA test = ...
anti-HEV IgM test = positive
anti-HEV IgG test = positive

waiting for input

HEV RNA test = ...
anti-HEV IgM test = positive
anti-HEV IgG test = negative

waiting for input

HEV RNA test = ...
anti-HEV IgM test = negative
anti-HEV IgG test = positive

waiting for input

HEV RNA test = ...
anti-HEV IgM test = negative
anti-HEV IgG test = negative

waiting for input

HEV RNA test = positive
anti-HEV IgM test = ...
anti-HEV IgG test = positive

waiting for input

HEV RNA test = positive
anti-HEV IgM test = ...
anti-HEV IgG test = ...

waiting for input

HEV RNA test = negative
anti-HEV IgM test = ...
anti-HEV IgG test = ...

waiting for input

HEV RNA test = negative
anti-HEV IgM test = negative
anti-HEV IgG test = ...

waiting for input

HEV RNA test = positive
anti-HEV IgM test = positive
anti-HEV IgG test = ...

waiting for input

HEV RNA test = ...
anti-HEV IgM test = ...
anti-HEV IgG test = negative

waiting for input

HEV RNA test = ...
anti-HEV IgM test = ...
anti-HEV IgG test = positive

waiting for input

HEV RNA test = negative
anti-HEV IgM test = ...
anti-HEV IgG test = negative

waiting for input

HEV RNA test = negative
anti-HEV IgM test = positive
anti-HEV IgG test = ...

waiting for input

HEV RNA test = positive
anti-HEV IgM test = negative
anti-HEV IgG test = ...

waiting for input

HEV RNA test = positive
anti-HEV IgM test = ...
anti-HEV IgG test = negative

waiting for input

HEV RNA test = negative
anti-HEV IgM test = ...
anti-HEV IgG test = positive

waiting for input

HEV RNA remains detectable = ...

waiting for input

HEV RNA remains detectable = positive

Chronic HEV infection
Continue with monthly HEV RNA monitoring.

HEV RNA remains detectable = negative

Cleared HEV infection.

End of test sequence