Should a patient with a reactive Hepatitis C Virus (HCV) Antibody (AB) test result be retested to confirm the diagnosis?

Should This Patient Be Retested for Hepatitis C?

Yes, this patient with a reactive HCV antibody test absolutely must undergo HCV RNA testing to determine if they have active infection versus past resolved infection. A positive antibody test alone cannot distinguish between current infection requiring treatment and past cleared infection. 1

Why Retesting is Mandatory

The reactive HCV antibody result indicates either:

• Active chronic infection (antibody positive + HCV RNA positive) - requires treatment evaluation 1
• Past resolved infection (antibody positive + HCV RNA negative) - no treatment needed 1
• Rarely, a false positive antibody test 2

Anti-HCV antibodies persist for years or even a lifetime after viral clearance, whether spontaneous or treatment-induced, making them useless for determining current infection status. 1 Only HCV RNA testing can definitively establish if active viral replication is occurring. 1

The Required Testing Algorithm

Immediate Next Step

• Order HCV RNA testing by a sensitive molecular method (lower limit of detection <15 IU/ml preferred, though <50 IU/ml is acceptable) 1
• Alternatively, HCV core antigen testing can be used if RNA testing is unavailable, though it is less sensitive 1

If HCV RNA is Positive

• This confirms active chronic HCV infection requiring medical evaluation and treatment 2, 3
• Proceed with quantitative HCV RNA, genotype testing, liver function assessment, and fibrosis staging 2, 3
• The goal of direct-acting antiviral therapy is viral eradication to prevent cirrhosis, hepatocellular carcinoma, and death 1, 3

If HCV RNA is Negative

This patient requires repeat HCV RNA testing 12-24 weeks later to confirm definitive viral clearance, particularly given their history of previous hepatitis treatment. 1 This is critical because:

• Brief periods of undetectable HCV RNA can occur even in active infection 1
• If this represents recently acquired infection, spontaneous clearance typically occurs within 4-6 months 1
• The 3-month retest window ensures you're not missing intermittent viremia 1

Critical Context for Previously Treated Patients

Since this patient was "previously treated for hepatitis," several scenarios require consideration:

If they achieved sustained virological response (SVR) from prior treatment:

• Anti-HCV antibodies remain positive indefinitely in most cases 1
• HCV RNA testing is the only way to detect reinfection in someone with ongoing risk factors 1, 2
• Reinfection rates range from 1-8% annually in high-risk populations (people who inject drugs, men who have sex with men) 4

If treatment status is unclear or they had prior treatment failure:

• HCV RNA testing immediately clarifies whether active infection persists 2, 3
• Modern direct-acting antivirals achieve >95% cure rates even in previously difficult-to-treat patients 3

Common Pitfalls to Avoid

• Never assume a positive antibody test alone means active infection - this leads to unnecessary treatment consideration in patients who have already cleared the virus 2, 3
• Never assume a single negative HCV RNA test in an antibody-positive patient represents definitive clearance - always retest at 12-24 weeks to confirm 1
• Don't confuse this scenario with acute hepatitis C screening - in suspected acute infection, both antibody and RNA should be tested simultaneously since antibodies may not yet be detectable 1

Bottom Line

The reactive HCV antibody test is only the first step in diagnosis - it triggers a mandatory reflex to HCV RNA testing. 1, 2 Without RNA confirmation, you cannot determine if this patient needs life-saving antiviral therapy or simply reassurance about past resolved infection. The distinction has profound implications for morbidity (preventing cirrhosis), mortality (preventing hepatocellular carcinoma and liver-related death), and quality of life (avoiding unnecessary treatment or missing needed treatment). 1, 3