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Hepatitis C virus (HCV) is recognized as the cause of most cases of post-transfusion hepatitis and is a significant cause of morbidity and mortality worldwide. In the United States, HCV infection is quite common, with an estimated 3.5 to 4 million chronic HCV carriers.
Laboratory testing for HCV infection usually begins by screening for the presence of HCV antibodies in serum, using an FDA-approved screening test. Specimens that are repeatedly reactive by screening tests should be confirmed with HCV tests with higher specificity, such as direct detection of HCV RNA by reverse transcription-PCR (RT-PCR) or HCV-specific antibody confirmatory tests.
HCV antibodies are usually not detectable during the first 2 months following infection, but they are usually detectable by the late convalescent stage (>6 months after onset) of infection. These antibodies do not neutralize the virus and they do not provide immunity against this viral infection. Decrease in the HCV antibody level in serum may occur after resolution of infection.
Current screening serologic tests to detect antibodies to HCV include EIA and chemiluminescence immunoassay. Despite the value of serologic tests to screen for HCV infection, several limitations of serologic testing exist:
-There may be a long delay (up to 6 months) between exposure to the virus and the development of a detectable HCV antibody
-False-reactive screening test result can occur
-A reactive screening test result does not distinguish between past (resolved) and present HCV infection
-Serologic tests cannot provide information on clinical response to anti-HCV therapy
Reactive screening test results should be followed by a supplemental or confirmatory test, such as nucleic acid test for HCV RNA or HCV antibody confirmatory test. Nucleic acid tests provide a very sensitive and specific approach for the direct detection of HCV RNA.
The following algorithms are available in Special Instructions:
-Testing Algorithm for the Diagnosis of Hepatitis C
Publications: Advances in the Laboratory Diagnosis of Hepatitis C (2002)
Detection and diagnosis of chronic hepatitis C virus infection in symptomatic patients
Reactive hepatitis C virus (HCV) antibody screening results with signal-to-cutoff (S/CO) ratios of <8.0 are not predictive of the true HCV antibody status and additional testing is recommended to confirm anti-HCV status. Reactive results with S/CO ratios of > or =8.0 are highly predictive (> or =95% probability) of the true anti-HCV status, but additional testing is needed to differentiate between past (resolved) and chronic hepatitis C.
A negative screening test result does not exclude the possibility of exposure to or infection with HCV. Negative screening test results in individuals with prior exposure to HCV may be due to low antibody levels that are below the limit of detection of this assay or lack of reactivity to the HCV antigens used in this assay. Patients with acute or recent HCV infections (<3 months from time of exposure) may have false-negative HCV antibody results due to the time needed for seroconversion (average of 8 to 9 weeks). Testing for HCV RNA (HCVQU / Hepatitis C Virus [HCV] RNA Detection and Quantification by Real-Time Reverse Transcription-PCR [RT-PCR], Serum) is recommended for detection of HCV infection in such patients.
The quantification range of this test is 15 to 100,000,000 IU/mL.
Negative results indicate that HCV RNA is not detected in the serum.
A numerical result indicates the presence of HCV infection with active viral replication.
Positive results with the comment of "HCV RNA detected, but <15 IU/mL" indicate that the HCV RNA present is at a level below the quantifiable lower limit of this assay. Follow-up testing by this assay is recommended in 1 to 3 months.
Positive results with the comment of "but >100,000,000 IU/mL" indicate that the level of HCV RNA present is above the quantifiable upper limit of this assay.
A single negative HCV RNA result with positive HCV antibody status (assay signal-to-cutoff ratio of > or =3.8 by EIA, or > or =8.0 by chemiluminescence immunoassay), does not necessarily indicate past or resolved HCV infection. Individuals with such results should be retested for HCV RNA in 1 to 2 months, to distinguish between patients with past or resolved HCV infection and those with chronic HCV infection having episodic HCV replication.
Presence of anti-HCV antibodies (assay signal-to-cutoff ratio of <3.8 by EIA or <8.0 by chemiluminescence immunoassay) in individuals with negative HCV RNA results may be confirmed HCV Antibody Confirmation, Serum.
This test is not offered as a screening or confirmatory test for hepatitis C virus (HCV) blood or human cells/tissue donors.
Indicate if specimens are from autopsy/cadaver or hemolyzed sources so that the proper FDA-licensed assay can be performed.
This test profile is not useful for detection or diagnosis of acute HCV, since HCV antibodies may not be detectable until after 2 months following exposure and HCV RNA testing is not performed on specimens with negative anti-HCV screening test results. Initial testing for HCV RNA (HCVQU / Hepatitis C Virus [HCV] RNA Detection and Quantification by Real-Time Reverse Transcription-PCR [RT-PCR], Serum) is recommended for detection of HCV infection in such patients.
A single negative HCV RNA test result together with a reactive HCV antibody screen result with a S/CO ratio of > or =8.0 do not rule out the possibility of chronic HCV infection. Repeat testing for HCV RNA in 1 to 2 months is recommended in patient at risk for chronic hepatitis C.
Infants born to HCV-infected mothers may have false-reactive HCV antibody test results due to transplacental passage of maternal HCV IgG antibodies. HCV antibody testing is not recommended until at least 18 months of age in these infants.
Performance characteristics have not been established for the following types of serum specimen:
-Individuals <10 years of age
-Grossly icteric (total bilirubin level of >20 mg/dL)
-Grossly lipemic (triolein level of >3,000 mg/dL)
-Grossly hemolyzed (hemoglobin level of >500 mg/dL)
-Presence of particulate matter
See Viral Hepatitis Serologic Profiles in Special Instructions.
1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C. Semin Liver Dis 2000;20(2):159-171
2. Pawlotsky JM: Use and interpretation of virological tests for hepatitis C. Hepatology 2002;36:S65-S73
3. Centers for Disease Control and Prevention: Testing for HCV infection: an update of guidance for clinicians and laboratorians. Morb Mortal Wkly Rep 2013;62(18):362-365
4. American Association for the Study of Liver Diseases / Infectious Diseases Society of America / International Antiviral Society–USA. Recommendations for Testing, Managing, and Treating Hepatitis C. www.hcvguidelines.org. Accessed on January 27, 2015