From the Guidelines
False positive results for hepatitis C virus antibody (HCV ab) testing can occur due to several factors, and when suspected, confirmation with an HCV RNA test is essential to distinguish between true and false positive antibody results. The causes of false positive HCV antibody results include cross-reactivity with other infections, autoimmune disorders, hypergammaglobulinemia, recent vaccinations, and laboratory errors. Some populations are at higher risk of false positives, such as pregnant women, elderly individuals, and those with renal disease on hemodialysis. According to the most recent guidelines 1, if testing is desired to distinguish between true positivity and biologic false positivity for HCV antibody, then testing may be done with a second HCV antibody assay approved by FDA for diagnosis of HCV infection that is different from the assay used for initial antibody testing. Key points to consider in the diagnosis of HCV infection include:
- The use of nucleic acid amplification tests (NAATs) for HCV RNA detection, which can be performed qualitatively or quantitatively 1
- The importance of confirmatory testing for HCV RNA in patients with positive HCV antibody screening test results 1
- The need to consider the clinical context and patient population when interpreting HCV antibody test results, as false positives may be more common in low-prevalence settings 1. In clinical practice, confirmation with an HCV RNA test is crucial to determine the presence of active HCV infection and to distinguish between true and false positive antibody results.
From the Research
Causes of False Positive HCV Antibody Results
- False-positive HCV antibody results can occur due to various factors, including the type of assay used 2, 3, 4
- The use of first-generation enzyme-linked immunosorbent assay (ELISA) tests can lead to false-positive results, especially in patients with autoimmune hepatitis 2
- Cross-reaction of an epitope of HCV can also cause false-positive results 2
- Very low levels of HCV antibodies can predict false-positive results, and a signal-to-cutoff (S/CO) ratio of less than 4.5 can be used to identify false-positive results 4
- Anti-influenzal vaccination can induce false-positive ELISA reactions for HCV in some individuals, especially in older adults 5
Factors Influencing False Positive Results
- The prevalence of HCV infection in the population being tested can affect the frequency of false-positive results, with lower prevalence populations having a higher likelihood of false-positive results 3
- The type of confirmatory test used, such as recombinant immunoblot assay (RIBA) or HCV RNA testing, can also impact the accuracy of results 2, 3, 4
- The presence of other viral markers, such as hepatitis B virus (HBV) infection, can also influence the interpretation of HCV antibody results 6
Implications of False Positive Results
- False-positive HCV antibody results can lead to unnecessary further testing and treatment, as well as significant morbidity and mortality associated with chronic HCV infection 3
- It is essential to confirm HCV antibody results using supplemental testing, such as RIBA or HCV RNA testing, to avoid false-positive results and ensure accurate diagnosis and treatment 2, 3, 4