What is the next step after a positive Hepatitis C (HCV) antibody test?

Next Steps After a Positive Hepatitis C Antibody Test

After a positive Hepatitis C (HCV) antibody test, the next step should be HCV RNA testing by nucleic acid testing (NAT) to determine if active infection is present. 1

Testing Algorithm

1. Initial positive HCV antibody test

   • A reactive HCV antibody result indicates one of three possibilities:
     • Current HCV infection
     • Past HCV infection that has resolved
     • False positive result

2. Reflex to HCV RNA testing

   • This is the critical next step to determine active infection
   • Can be performed on the same blood sample (reflex testing) or require a new sample
   • HCV RNA is a marker for viremia and is only detected in currently infected persons 1

3. Interpretation of HCV RNA results:

   • If HCV RNA is detected:

     • Confirms current active HCV infection
     • Patient should receive appropriate counseling
     • Link patient to medical care and treatment 1

   • If HCV RNA is not detected:

     • Indicates either resolved past infection or false positive antibody
     • In most cases, no further action is required
     • Consider supplemental antibody testing if distinction between true positivity and false positivity is desired 1

Special Considerations

• Recent exposure (within past 6 months):

  • Consider HCV RNA testing even with negative antibody results
  • HCV RNA can be detected as early as 1-2 weeks after exposure, while antibodies may take 5-6 weeks or longer to develop 2

• Immunocompromised patients:

  • May have delayed seroconversion or persistently negative antibody tests despite infection
  • Consider HCV RNA testing if clinical suspicion exists 1

• Indeterminate antibody results:

  • May indicate recent infection in the process of seroconversion
  • Collect another sample for repeat anti-HCV testing (>1 month later) or perform HCV RNA testing 1

Follow-up Management

For patients with confirmed active HCV infection (HCV RNA positive):

1. Initial evaluation:

   • Complete blood count, liver function tests, assessment for advanced fibrosis
   • Counsel on alcohol abstinence to prevent liver disease progression 3
   • Vaccinate against hepatitis A and B if not immune 3

2. Linkage to care:

   • Refer for evaluation for antiviral therapy
   • Direct-acting antiviral (DAA) therapy is the standard of care 3
   • Treatment selection based on HCV genotype, presence of cirrhosis, prior treatment history

3. Prevention counseling:

   • Discuss modes of transmission and prevention of reinfection
   • Avoid sharing needles and personal care items that may have blood on them 3

Common Pitfalls to Avoid

1. Misinterpreting a positive antibody test as active infection

   • Up to 25% of adults who acquire HCV infection spontaneously clear the virus 1
   • Only HCV RNA testing can confirm current infection

2. Missing intermittent viremia

   • Intermittent HCV RNA positivity can occur in chronic infection
   • If clinical suspicion is high despite negative HCV RNA, consider repeat testing 1

3. Inadequate follow-up for patients with advanced fibrosis

   • Patients with advanced fibrosis or cirrhosis require continued surveillance for hepatocellular carcinoma even after achieving cure 3

4. Relying solely on signal-to-cutoff ratios

   • While some laboratories use signal-to-cutoff ratios to predict true positivity, HCV RNA testing remains the definitive next step for all positive antibody results 4

By following this evidence-based algorithm, clinicians can accurately diagnose active HCV infection, appropriately counsel patients, and link them to necessary care and treatment to prevent complications including cirrhosis, hepatocellular carcinoma, and death.