From the Guidelines
A person with a positive Hepatitis C Virus Antibody (HCV AB) test and a negative Hepatitis C Virus Ribonucleic Acid (HCV RNA) test has likely cleared the Hepatitis C virus, as the presence of HCV antibodies indicates past exposure, while the absence of HCV RNA suggests the virus is no longer actively replicating in their body.
Key Points
- The combination of HCV AB positive and HCV RNA negative results indicates that the individual has been exposed to the virus at some point, but the virus is no longer detectable in their body 1.
- This outcome can occur either spontaneously, without treatment, or as a result of successful antiviral therapy.
- According to the American Association for the Study of Liver Diseases-Infectious Diseases Society of America recommendations, persons with a positive HCV-antibody test and negative HCV RNA results should be informed that they do not have evidence of current (active) HCV infection, but are not protected from reinfection 1.
- Quantitative HCV-RNA testing is recommended prior to initiation of antiviral therapy to document the baseline level of viremia (i.e., baseline viral load) 1.
- HCV genotype testing may be considered for those in whom it may alter treatment recommendations, such as persons with a prior HCV treatment failure 1.
- If the distinction between true positivity and biologic false positivity for HCV antibody is desired, testing with another HCV antibody assay can be undertaken, as a false positive typically does not occur with two different assays 1.
From the Research
Interpretation of HCV AB and HCV RNA Test Results
- A positive Hepatitis C Virus Antibody (HCV AB) test indicates that the individual has been exposed to the Hepatitis C virus at some point in their lives, as the test detects the presence of antibodies against the virus in the blood 2.
- A negative Hepatitis C Virus Ribonucleic Acid (HCV RNA) test, on the other hand, suggests that the virus is not currently active in the individual's blood, as this test detects the genetic material of the virus 2, 3.
Possible Scenarios
- One possible scenario is that the individual has been infected with Hepatitis C in the past, but has since cleared the virus, resulting in a positive HCV AB test and a negative HCV RNA test 3, 4.
- Another possibility is that the individual has a false-positive HCV AB test result, which can occur in populations with low HCV prevalence, as seen in the National Health and Nutrition Examination Study (NHANES) 2007-2012 4.
- It is also possible that the virus is present in the individual's peripheral blood mononuclear cells (PBMC), but not in their plasma, resulting in a negative HCV RNA test, as detected in some HCV-seropositive subjects without viremia 3.
Clinical Implications
- In any case, a positive HCV AB test should be followed by an HCV RNA test to confirm whether the individual has a current infection, as recommended by studies 2, 4.
- If the HCV RNA test is negative, further testing and evaluation may be necessary to determine the individual's infection status and to rule out other possible causes of the positive HCV AB test result.