What is the recommended treatment for a patient with a negative Hepatitis C Virus (HCV) RNA Quant result but positive status for hepatitis C?

Management of HCV Antibody-Positive, HCV RNA-Negative Patient

This patient most likely has either a false-positive HCV antibody test or has spontaneously cleared a prior HCV infection, and the critical next step is to perform repeat HCV antibody testing using a different assay platform to distinguish between these two scenarios. 1

Immediate Diagnostic Algorithm

Step 1: Repeat HCV Antibody Testing on Alternative Platform

• Perform confirmatory anti-HCV testing using a different antibody assay platform (not the same test that gave the initial positive result) 1
• This supplemental antibody testing is essential to eliminate false-positive results and confirm whether anti-HCV truly indicates past or current infection 2

Step 2: Interpret Results Based on Confirmatory Testing

If the alternative antibody assay is NEGATIVE:

• The initial test was a false-positive 1
• No HCV infection is present—the patient does not have and never had hepatitis C 1
• No further HCV evaluation is needed unless new risk exposures occur 1
• Reassure the patient they are not infected with HCV 1

If the alternative antibody assay is POSITIVE:

• This confirms the patient had HCV infection that has spontaneously cleared 1
• Approximately 15-45% of HCV infections clear spontaneously (higher rates in younger patients: 40-45% if infected as children/young adults; 15-25% if infected at older ages) 1
• The patient does not have active HCV infection and does not require antiviral treatment 1
• No follow-up HCV testing is needed 1

Special Circumstances Requiring Additional HCV RNA Testing

Even with confirmed positive antibodies and negative HCV RNA, repeat HCV RNA testing should be considered in these specific situations 1:

• Recent exposure within the past 6 months (may be in early acute infection window) 1
• Clinical evidence of ongoing liver disease (elevated ALT, signs of hepatic inflammation) 2, 1
• Immunocompromised patients (HIV coinfection, transplant recipients, immunosuppressive therapy) 2, 1
• Concerns about specimen handling or storage that may have degraded HCV RNA 1

The rationale is that HCV RNA can be intermittently positive in some patients with chronic infection, and a single negative result does not definitively exclude active infection without additional clinical context 2, 1

Critical Pitfalls to Avoid

Do Not Assume Single Negative HCV RNA Rules Out Infection

• Without confirmatory antibody testing on an alternative platform, you cannot distinguish between false-positive antibody results and true cleared infection 1
• The absence of HCV RNA in a person with anti-HCV-positive result based on EIA testing alone cannot differentiate between resolved infection and a false-positive anti-HCV test 2

Do Not Miss Early Acute Infection

• If exposure occurred within 4-6 weeks, the patient may be in the window period where antibodies are not yet detectable but HCV RNA would be positive 2
• In suspected acute hepatitis C, HCV RNA testing should be part of the initial evaluation even if anti-HCV is negative 2

Do Not Order Unnecessary Repeat Testing

• Once cleared infection is confirmed (positive antibody on two different platforms, negative HCV RNA), no further HCV testing is indicated 1
• Patients with confirmed cleared infections do not need ongoing monitoring unless new risk exposures occur 1

Clinical Context Matters

If Patient Has Risk Factors or Symptoms

• Evaluate for other causes of liver disease if ALT is elevated 2
• Test for other hepatotropic viruses (HBV) and HIV 2
• Assess alcohol consumption and metabolic risk factors 2

If Patient Is Immunosuppressed

• Lower threshold for repeat HCV RNA testing, as these patients may have delayed antibody responses or intermittent viremia 2, 1
• Consider testing HCV RNA 4-6 weeks after exposure for early diagnosis 2

Summary of Management Pathway

1. Repeat anti-HCV on different platform → If negative: false-positive, no infection 1
2. If repeat anti-HCV positive → Cleared infection, no treatment needed 1
3. Consider repeat HCV RNA only if: recent exposure, liver disease, immunosuppressed, or specimen concerns 1
4. Do not treat patients with negative HCV RNA (unless special circumstances warrant repeat testing that becomes positive) 1