What does a Hepatitis C (HCV) antibody reactive result indicate?

Hepatitis C Antibody Reactive Result Interpretation

A reactive (positive) Hepatitis C antibody test indicates presumptive HCV infection that requires confirmatory HCV RNA testing to determine if the person has current HCV infection or past infection that has resolved. 1

Understanding HCV Antibody Reactivity

A reactive HCV antibody test can indicate one of three possibilities:

• Current HCV infection
• Past HCV infection that has resolved
• Biologic false positivity for HCV antibody 1

Confirmatory Testing Required

When an HCV antibody test is reactive, the following steps should be taken:

1. HCV RNA testing is essential to determine if active infection is present

   • If HCV RNA is detected: Current HCV infection is confirmed 1
   • If HCV RNA is not detected: No current HCV infection (either resolved past infection or false positive antibody) 1

2. For reactive antibody with undetected HCV RNA:

   • In most cases, no further action is required
   • If distinction between true past infection and false positivity is desired, testing with another HCV antibody assay (such as RIBA) may be performed 1

Interpreting Test Specificity

The specificity of HCV antibody tests is high (>99%), but false positives still occur:

• In low-prevalence populations (<10%), false-positive rates average approximately 35% (range: 15%-60%) 1
• In immunocompromised populations (e.g., hemodialysis patients), false-positive rates average approximately 15% 1

Signal-to-Cutoff (S/CO) Ratio Importance

The S/CO ratio provides valuable information about the likelihood of a true positive result:

• Higher S/CO ratios correlate with higher likelihood of true HCV infection 2
• Results can be classified into levels (low and high, or very low, low, and high) based on S/CO ratio:
  • Very low level: Likely false-positive, no further testing needed
  • Low level: Possible false-positive, immunoblot testing recommended
  • High level: Accurate marker for predicting viremia, HCV RNA testing needed 2

Clinical Implications

If HCV RNA is detected (confirming current infection):

• The patient requires appropriate counseling and linkage to medical care and treatment 1
• Before initiating antiviral therapy, retesting for HCV RNA in a subsequent blood sample is recommended to confirm HCV RNA positivity 1

Special Considerations

1. Recent exposure: If exposure occurred within the past 6 months, HCV RNA testing is recommended even with a non-reactive antibody test, as antibodies may not have developed yet (window period) 3

2. Immunocompromised patients: These individuals may have impaired antibody production and remain persistently anti-HCV negative despite active infection, requiring direct HCV RNA testing 3

3. Antibody persistence: In most immunocompetent patients who clear the virus naturally, HCV antibodies persist for years, though partial or complete seroreversion (loss of antibodies) may occur over time 4

Reporting Requirements

"Acute hepatitis C" and "hepatitis C (past or present)" are nationally notifiable conditions subject to mandated reporting to health departments by clinicians and laboratorians in most jurisdictions 1

Remember that a reactive HCV antibody test alone is not sufficient for diagnosis of current HCV infection, and HCV RNA testing is essential for determining the current infection status.