Hepatitis C Antibody Screen, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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 (anti-HCV) in serum, using an FDA-approved anti-HCV screening test. Specimens that are repeatedly reactive by screening tests should be confirmed by more HCV-specific tests, such as direct detection of HCV RNA by reverse transcriptase-PCR (RT-PCR) or strip recombinant immunoblot assay (RIBA) using recombinant HCV-specific antigens.
HCV antibodies are usually not detected during the first 2 months following infection and are almost always 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. Loss of HCV antibodies may occur several years following resolution of infection.
Current screening serologic tests to detect HCV antibodies 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 detectable HCV antibodies.
-False-reactive screening test results can occur.
-A reactive screening test result does not distinguish between past (resolved) and chronic 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 RIBA for HCV antibodies or nucleic acid tests for HCV RNA. 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:
-Viral Hepatitis Serologic Profiles
-Testing Algorithm for the Diagnosis of Hepatitis C
Screening for past (resolved) or chronic hepatitis C
Reactive hepatitis C virus (HCV) antibody screening results with signal-to-cutoff (S/CO) ratios of <8.0 are not predicative 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.
To confirm results of HCV antibody screening test and to guide further management of patients, specimens should be tested by 1 of the following supplemental tests:
-HCVQU Hepatitis C Virus (HCV) RNA Detection and Quantification by Real-Time Reverse Transcription-PCR (RT-PCR), Serum for patients with known risk factors for HCV infection. Presence of HCV RNA in a given specimen indicates acute or chronic hepatitis C.
-RIBA/80181 Hepatitis C Virus Antibody Confirmation by Recombinant Immunoblot Assay (RIBA), Serum for patients with minimal or no risk factors for HCV infection. A positive RIBA result confirms the presence of HCV IgG antibodies, but it does not 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 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 test 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not offered as hepatitis C virus (HCV) screening or confirmatory testing for organ, blood, or human cell/tissue donors.
Indicate if specimens are from autopsy/cadaver or hemolyzed sources so that the proper FDA-licensed assay can be performed.
HCV serologic tests are not useful for detection of early or acute HCV infection, and they are not useful for differentiating between past (resolved) and chronic hepatitis C. 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 acute HCV infection.
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 of <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
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 depends on clinical setting.
See Viral Hepatitis Serologic Profiles in Special Instructions.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Carithers RL, Marquardt A, Gretch DR: Diagnostic testing for hepatitis C. Semin Liver Dis 2000;20(2):159-171
2. Alter MJ, Kuhnert WL, Finelli L: Centers for Disease Control and Prevention: guidelines for laboratory testing and result reporting of antibody to hepatitis C virus. MMWR Morb Mortal Wkly Rep 2003;52(RR-3):1-13
3. Germer JJ, Zein NN: Advances in the molecular diagnosis of hepatitis C and their clinical implications. Mayo Clin Proc 2001;76(9):911-920
4. Pawlotsky JM: Use and interpretation of virological tests for hepatitis C. Hepatology 2002;36:S65-S73