What are the next steps for a patient with a positive Hepatitis C Virus (HCV) antibody test and an undetectable HCV RNA level?

Management of a Patient with Positive HCV Antibody and Undetectable HCV RNA

The patient with positive HCV antibody and undetectable HCV RNA (<15 IU/ml) has spontaneously cleared the HCV infection and does not require HCV treatment, but should undergo fibrosis assessment to determine if there is residual liver damage requiring monitoring.

Interpretation of Test Results

When evaluating a patient with positive HCV antibody (anti-HCV) and undetectable HCV RNA (<15 IU/ml), the following interpretation applies:

• This pattern indicates one of the following scenarios 1:

  • Spontaneous clearance of past HCV infection (most likely)
  • False positive antibody test (less likely)

• HCV antibodies persist after viral clearance but may decline and eventually disappear in some individuals over time 1

• Undetectable HCV RNA (<15 IU/ml) confirms the absence of active viral replication 1

Next Steps in Management

1. Confirm Test Results

• Verify that the HCV RNA test used had adequate sensitivity (lower limit of detection <15 IU/ml) 1

• Consider repeating HCV RNA testing in 3 months to confirm sustained absence of viremia, especially if:

  • Recent exposure to HCV is suspected (within past 6 months)
  • Patient has clinical evidence of liver disease
  • There are concerns about specimen handling or storage 1

2. Differentiate Between Resolved Infection and False Positive

If there is uncertainty about whether this represents cleared infection versus false positive antibody:

• Consider testing with a different HCV antibody assay platform 1
  • If second antibody test is positive → confirms past, resolved infection
  • If second antibody test is negative → suggests initial false positive result

3. Assess for Liver Damage

• Proceed with the Fibrotest/Actitest as planned to assess for residual liver damage 1

• Additional baseline laboratory testing should include 1:

  • Complete hepatic function panel (bilirubin, ALT, AST, albumin)
  • Platelet count
  • Prothrombin time

4. Evaluate for Other Causes of Liver Disease

• Screen for other potential causes of liver disease if liver enzymes remain elevated despite HCV clearance 1

• Consider testing for other viral hepatitis (HBV, HAV) and metabolic causes of liver disease 1

Follow-up Recommendations

For Patients with No or Minimal Fibrosis

• No specific HCV-related follow-up is required if fibrosis assessment shows no or minimal liver damage 1

• Counsel on risk reduction strategies to prevent reinfection if patient has ongoing risk factors 1

For Patients with Advanced Fibrosis or Cirrhosis

• Continue surveillance for hepatocellular carcinoma (HCC) despite viral clearance 1

• Monitor for complications of cirrhosis if present 1

Risk of Reinfection

• Patients with ongoing risk factors (e.g., injection drug use, high-risk sexual practices) should be counseled about risk reduction 1

• Consider annual HCV RNA testing for those with ongoing risk behaviors 1, 2

Common Pitfalls to Avoid

1. Misinterpreting the results: A positive antibody with negative RNA does not indicate current infection requiring treatment 1

2. Failing to assess liver damage: Even with cleared infection, the patient may have residual liver fibrosis requiring monitoring 1

3. Overlooking reinfection risk: Patients who spontaneously cleared HCV can become reinfected if exposed again 1, 2

4. Missing intermittent viremia: Although rare, some patients may have intermittent detectable HCV RNA, which is why confirmation testing is sometimes recommended 1

5. Assuming normal liver enzymes mean no liver damage: Fibrosis assessment is important regardless of liver enzyme levels 1