Hepatitis C Antibody Screen Patient Source, 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 a 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 transcription-PCR (RT-PCR) or strip recombinant immunoblot assay (RIBA) using recombinant HCV-specific antigens.
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. Loss of HCV antibodies may occur in the year following resolution of infection.
Current screening serologic tests to detect antibodies to HCV include EIA and chemiluminescence immunoassay (CIA). 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 RIBA for HCV antibodies or a nucleic acid test for HCV RNA. Nucleic acid tests provide a very sensitive and specific approach for the direct detection of HCV RNA.
See Recommended Approach to the Diagnosis and Monitoring of Patients with Hepatitis C Virus in Special Instructions.
Detection and diagnosis of chronic hepatitis C virus infection
Screening test (CIA):
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 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).
The quantification range of this test is 43 IU/mL to 69,000,000 IU/mL.
Negative results indicate that HCV RNA is not detected in the serum.
A titer result indicates the presence of HCV infection with active viral replication.
Positive results with the comment of "HCV RNA detected, but less than 43 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 greater than 69,000,000 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 anti-HCV antibody status (assay signal-to-cutoff ratio of > or =3.8 by EIA, or > or =8.0 by chemiluminescence immunoassay [CIA]), 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/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 CIA) in individuals with negative HCV RNA results may be confirmed by RIBA/80181 Hepatitis C Virus Antibody (Anti-HCV) Confirmation, Serum.
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.
This test profile is not useful for detection or diagnosis of acute hepatitis C, 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.
A single negative HCV RNA test result together and 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 of less than 10 years of age 13009 (HCVPS)
-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.
HCV ANTIBODY SCREEN PATIENT SOURCE
Negative (reported as reactive or negative)
HEPATITIS C RT-PCR
Negative for HCV-RNA
If positive, reported as positive for HCV-RNA
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(No. RR-3):1-14
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