From the Guidelines
False positive Hepatitis C (HCV) antibody tests can occur due to several factors, including cross-reactivity with other viral infections, autoimmune disorders, immunizations, hypergammaglobulinemia, and laboratory errors, as noted in the 2020 guidelines for hepatitis C testing and management 1.
Causes of False Positives
Some of the key factors that can lead to false positive results include:
- Cross-reactivity with other viral infections, such as Epstein-Barr virus, cytomegalovirus, or other flaviviruses
- Autoimmune disorders like rheumatoid arthritis, systemic lupus erythematosus, and mixed cryoglobulinemia, which can trigger false positives due to the presence of autoantibodies that may bind non-specifically in the test
- Immunizations, particularly influenza vaccines, which can temporarily cause false positive results
- Hypergammaglobulinemia, a condition with elevated immunoglobulin levels, which can interfere with test accuracy
- Laboratory errors during sample handling or processing, which may also contribute to false positives
Populations at Higher Risk
Certain populations have higher false positive rates, including:
- Elderly individuals
- Those from low-prevalence regions, as discussed in the guidelines for laboratory testing and result reporting of antibody to hepatitis C virus 1
Importance of Confirmation Testing
When a positive antibody test occurs, confirmation with an HCV RNA test is essential to determine if active infection is present, as approximately 15-25% of people naturally clear the virus after infection while retaining antibodies 1. This two-step testing approach helps distinguish between past resolved infections and current active infections requiring treatment. According to the 2020 guidelines, HCV-antibody testing with reflex HCV RNA polymerase chain reaction testing is recommended for initial HCV screening 1.
From the Research
Causes of False Positive Hepatitis C Antibody Test
- Autoimmune hepatitis: Studies have shown that patients with autoimmune hepatitis may test positive for Hepatitis C antibodies, even in the absence of viral RNA 2.
- Cross-reaction of an epitope of HCV: This can occur when the immune system mistakes a similar protein for the HCV antibody, leading to a false positive result 2.
- Previous infection with HCV: It is possible that a previous infection with HCV can lead to a false positive result, even if the virus is no longer present 2.
- High IgM levels: Research has found that patients with acute viral hepatitis and high IgM levels are more likely to have false positive antibodies 3.
- Elevated ESR: Elevated erythrocyte sedimentation rate (ESR) has also been associated with false positive antibodies in acute HCV 3.
- Laboratory error: False positive results can also occur due to laboratory error or contamination 4, 5.
Factors that Increase the Risk of False Positive Results
- Use of certain antibody tests: Some antibody tests, such as ELISA-I and ELISA-II, are more prone to false positive results than others, such as RIBA-II 2, 5.
- Lack of confirmatory testing: Failure to perform confirmatory testing, such as HCV-RNA assay, can lead to false positive results being reported as true positives 4, 6.
- Presence of other medical conditions: Certain medical conditions, such as autoimmune disorders, can increase the risk of false positive results 2.