What is HCV (Hepatitis C Virus) ab (antibody)?

What is HCV Antibody (Anti-HCV)?

HCV antibody (anti-HCV) is a serologic marker that indicates exposure to hepatitis C virus, detected through screening immunoassays, but a positive result requires confirmatory testing with HCV RNA to distinguish between current infection, past resolved infection, or false-positive results. 1

Definition and Clinical Significance

• Anti-HCV represents antibodies produced by the immune system in response to hepatitis C virus infection, first becoming detectable approximately 6-10 weeks after the onset of clinical illness 1
• The presence of anti-HCV alone does NOT confirm active infection—it only indicates that exposure to HCV has occurred at some point 1
• Anti-HCV antibodies persist indefinitely in most patients, even after spontaneous or treatment-induced viral clearance, making them unsuitable as sole markers of active disease 1

Testing Algorithm and Interpretation

• Initial screening uses enzyme immunoassays (EIA) or rapid diagnostic tests (RDTs) to detect anti-HCV in serum, plasma, fingerstick whole blood, or oral fluid 1
• All positive anti-HCV screening results must be followed by HCV RNA testing (nucleic acid amplification test) to confirm active viral replication and current infection 1
• The CDC recommends reflex HCV RNA testing on the same blood sample used for antibody screening to improve linkage to care and reduce loss to follow-up 1

Critical Distinctions Based on Test Results

Anti-HCV positive + HCV RNA positive:

• Confirms current, active HCV infection requiring treatment evaluation 1
• Indicates ongoing viral replication and potential for transmission 2, 3

Anti-HCV positive + HCV RNA negative:

• May represent past resolved infection (15-45% of cases, depending on age at infection) 1
• Could indicate false-positive antibody result, particularly in low-prevalence populations where false-positive rates average 15% 1
• Requires supplemental testing with recombinant immunoblot assay (RIBA) or repeat HCV RNA testing after 3 months to clarify status 1

Anti-HCV negative:

• Generally indicates no HCV infection 1
• Exception: False-negatives occur during the acute infection window period (first 6-10 weeks), in immunocompromised patients (who may have delayed seroconversion up to 6 months), and rarely in chronic infection 1

Common Clinical Pitfalls

• Do not assume anti-HCV positivity alone confirms active infection requiring treatment—HCV RNA must be detected 3, 4
• In populations with low HCV prevalence (<10%), false-positive anti-HCV results are common, making confirmatory testing essential to avoid unnecessary psychological harm and medical interventions 1
• Immunocompromised patients (including those on hemodialysis, HIV-positive individuals, or transplant recipients) may remain anti-HCV negative despite active infection, requiring direct HCV RNA or core antigen testing 1, 5
• Intermittent viremia can occur in chronic HCV infection, so a single negative HCV RNA result does not definitively exclude active disease 1

Signal-to-Cutoff (S/CO) Ratios

• Modern anti-HCV assays generate S/CO ratios that predict the likelihood of true-positive results 1
• High S/CO ratios strongly correlate with active viremia and reduce the need for supplemental antibody testing before proceeding to HCV RNA confirmation 1, 6
• Very low S/CO ratios typically represent false-positive results and do not require further testing 6

Alternative Testing: HCV Core Antigen

• HCV core antigen is a surrogate marker of viral replication that can replace HCV RNA testing when molecular assays are unavailable or unaffordable 1
• Core antigen assays are less sensitive than HCV RNA (detection threshold equivalent to 500-3,000 IU/mL), causing delayed detection in acute infection and potential false-negatives in low-level viremia 1, 5
• Core antigen testing is particularly useful for screening at-risk populations, immunocompromised hosts, and hemodialysis patients where antibody responses may be unreliable 5