Test Catalog

Test ID: HEVQU    
Hepatitis E Virus RNA Detection and Quantification by Real-Time RT-PCR, Serum

Useful For Suggests clinical disorders or settings where the test may be helpful

Virologic detection and confirmation of hepatitis E virus (HEV) infection in immunocompromised individuals at risk for or suspected to have acute or chronic hepatitis E


Monitoring HEV RNA levels and determining eradication of chronic HEV infection in immunocompromised individuals

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Hepatitis E virus (HEV) is a causative agent of acute self-limited or fulminant hepatitis. HEV has been responsible for large outbreaks of disease in developing countries, primarily through waterborne transmission. Hepatitis E also can occur in industrialized countries, usually as sporadic cases due to zoonotic infection transmitted by the fecal-oral route. A major natural reservoir of HEV is pigs.


In immunocompetent individuals, hepatitis E is mainly a self-limited infection, frequently non-symptomatic and does not result in chronic infection. However, in otherwise healthy pregnant patients, hepatitis E can be severe resulting in significant morbidity and mortality. In immunocompromised individuals, such as organ transplant recipients, hepatitis E can be chronic with detectable HEV RNA levels in serum and plasma beyond 3 months after infection. HEV-specific IgM antibody is detectable by serologic testing by 4 weeks after infection in immunocompetent individuals, but it may not be detectable until 6 months after infection in immunosuppressed patients.


HEV RNA levels in serum or plasma are usually detectable in all infected individuals by 3 weeks after infection and become undetectable by 7 weeks in immunocompetent individuals. Due to the limitations of HEV serologic testing in immunosuppressed patients, molecular testing (eg, RT-PCR assay) for HEV RNA in serum or plasma is an increasingly important tool in the diagnosis of acute or chronic HEV infection in these patients.


Currently, ribavirin is used as the antiviral agent of choice for organ transplant recipients with chronic HEV, and monitoring of HEV RNA levels in serum or plasma is used to assess response to such antiviral therapy. Significant decreases in HEV viral load or clearance of HEV RNA may be important predictors of virologic response during antiviral therapy.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Interpretation Provides information to assist in interpretation of the test results

The quantification range of this assay is 100 to 5,000,000 IU/mL (2.00 log to 6.70 log IU/mL), with a limit of detection (based on a 95% detection rate) of 11 IU/mL (1.04 log IU/mL).


An "Undetected" result indicates that hepatitis E virus (HEV) RNA is not detected in the serum specimen (see Cautions). Repeat testing in 1 to 2 months is recommended for those at risk of HEV infection. The limit of detection (based on a 95% detection rate) for this assay is 11 IU/mL.


A result of "<100 IU/mL" indicates that the HEV RNA level present in the serum specimen is below 100 IU/mL (2.00 log IU/mL), and the assay cannot accurately quantify the HEV RNA present below this level.


A quantitative value (reported in IU/mL and log IU/mL) indicates the HEV RNA level (ie, viral load) present in the serum specimen.


A result of ">5,000,000 IU/mL" indicates that the HEV RNA level present in the serum specimen is above 5,000,000 IU/mL (6.70 log IU/mL), and this assay cannot accurately quantify the HEV RNA present above this level.


An "Indeterminate" result suggests the presence of an atypical HEV target sequence. Since the HEV RNA sequence is atypical, repeat testing is unlikely to change this result and therefore is not recommended.


An "Equivocal" result indicates that the presence or absence of HEV RNA in the serum specimen could not be determined with certainty due to atypical RT-PCR probe reactivity. Submission of a new specimen for testing is recommended.


An "Inconclusive" result indicates that the presence or absence of HEV RNA in the serum specimen could not be determined with certainty after repeat testing in the laboratory, possibly due to RT-PCR inhibition. Submission of a new specimen for testing is recommended.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This assay is optimized for the detection and quantification of Hepatitis E virus (HEV) genotypes 1 to 4, but due to unexpected mismatches between the RT-PCR primers and unusual or rare HEV target sequences, some serum specimens may yield "Undetected" results despite the presence of HEV RNA. Therefore, results should be interpreted with caution, considering the patient's risk factors for HEV infection, the analytical sensitivity of the assay, and possible source of the infecting HEV strain. Follow-up HEV RNA testing is recommended for patients with initially "Undetected" HEV RNA test results but at high risk for or suspected to have chronic hepatitis E.


In immunocompetent individuals, undetectable HEV RNA results indicate only the absence of HEV RNA in the specimen tested and do not exclude the diagnosis of HEV infection, given the relatively short duration of viremia (3 to 7 weeks after infection) in these individuals. Immunocompetent individuals with HEV infection would be expected to have repeatedly positive HEV-specific antibody test results (anti-HEV IgM and/or anti-HEV IgG).


Due to potential differences in assay performance, serial monitoring of HEV viral load in a given patient should be performed with the same molecular assay.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Aggarwal R: Diagnosis of hepatitis E. Nat Rev Gastroenterol Hepatol 2013;10(1):24-33

2. Kamar N, Rostaing L, Izopet J: Hepatitis E virus infection in immunosuppressed patients: natural history and therapy. Semin Liver Dis 2013;33:62-70

3. Kamar N, Lhome S, Abravanel F, et al: An early viral response predicts the virological response to ribavirin in hepatitis E virus organ transplant patients. Transplantation 2015;99(10):2124-2131

4. Germer JJ, Ankoudinova I, Belousov YS, et al: Hepatitis E virus detection and quantification by an RT-qPCR assay calibrated to the World Health Organization Standard for HEV RNA. J Clin Microbiol 2017; February, doi: 10.1128/JCM.02334-16

Special Instructions Library of PDFs including pertinent information and forms related to the test