What is a hepatitis C titer?

What is a Hepatitis C Titer?

A hepatitis C titer refers to the quantitative measurement of HCV RNA (viral load) in the bloodstream, expressed in international units per milliliter (IU/mL), which indicates the amount of actively replicating virus present in a patient's blood. 1

Understanding HCV Titer vs. Antibody Testing

The term "titer" in hepatitis C can refer to two distinct measurements, and it's critical to distinguish between them:

HCV RNA Viral Load (The True "Titer")

• Quantitative nucleic acid tests (NATs) measure the actual amount of virus circulating in the blood, reported as IU/mL. 1
• Modern quantitative HCV RNA assays using real-time PCR or transcription-mediated amplification have a lower detection limit of 12-15 IU/mL and an upper limit of 7-8 log IU/mL. 1
• This viral load measurement is critical for monitoring treatment effectiveness, but it does NOT correlate with disease severity or stage of liver fibrosis. 1

Anti-HCV Antibody Levels

• Anti-HCV antibody tests can also produce a semi-quantitative result, often reported as a signal-to-cutoff (S/CO) ratio. 1
• However, antibody levels are NOT used for clinical decision-making regarding disease activity or treatment. 1
• Antibodies persist indefinitely after infection, whether the infection is chronic or has resolved, making them unsuitable for determining current infection status. 1

Clinical Significance of Viral Load

What Viral Load Does Tell You

• Viral load is essential for confirming active infection in anti-HCV positive patients. 1
• It serves as a baseline measurement before treatment initiation. 1
• Quantitative HCV RNA is the definitive marker for treatment response and cure (sustained virological response = undetectable HCV RNA 12 weeks post-treatment). 2

What Viral Load Does NOT Tell You

• Viral load does not predict disease severity, degree of liver inflammation, or stage of fibrosis. 1
• Higher viral loads do not necessarily mean worse liver disease. 1
• Liver enzyme levels (ALT) also fluctuate independently of viral load and don't reliably correlate with disease stage. 1

Diagnostic Algorithm

When ordering HCV testing, follow this sequence: 1

1. First-line test: Anti-HCV antibody (highly sensitive and specific screening test). 1

2. If anti-HCV positive → Reflex to quantitative HCV RNA testing (ideally automatic to avoid loss to follow-up). 1

3. Interpretation:

   • Anti-HCV positive + HCV RNA detected = Active chronic infection requiring treatment. 1
   • Anti-HCV positive + HCV RNA not detected = Past resolved infection or false positive antibody. 3
   • Anti-HCV negative + high clinical suspicion (recent exposure, immunocompromised) = Consider direct HCV RNA testing. 1

Common Pitfalls to Avoid

• Don't use viral load to stage liver disease – use noninvasive fibrosis markers or liver biopsy instead. 1
• Don't assume negative antibodies rule out infection in immunocompromised patients (HIV, hemodialysis, transplant recipients) – they may have delayed or absent seroconversion. 1
• Don't confuse antibody positivity with active infection – always confirm with HCV RNA testing. 1
• Don't order genotyping routinely – with modern pangenotypic direct-acting antivirals, genotyping is only needed for treatment-experienced patients with prior treatment failure. 1

Special Considerations

• In acute hepatitis C, HCV RNA becomes detectable as early as 1-2 weeks after infection, while antibodies appear at 8-9 weeks on average. 1
• For patients with anti-HCV positive but HCV RNA negative results, repeat RNA testing in 3 months if ongoing risk factors exist or recent exposure is suspected. 1
• HCV core antigen can serve as a surrogate marker for viral replication when RNA testing is unavailable, though it's less sensitive (detection threshold ~500-3000 IU/mL). 1