What labs are recommended for patients with Hepatitis C (HCV)?

Laboratory Testing for Hepatitis C Virus Infection

Initial Diagnostic Testing

All patients being evaluated for HCV infection should first undergo HCV antibody testing with reflex HCV RNA PCR testing using a single blood draw. 1 This two-step reflex approach eliminates the need for return visits and addresses a major barrier in the HCV care continuum. 1

Step 1: HCV Antibody Testing

• Use an FDA-approved anti-HCV antibody assay (enzyme immunoassay or rapid test) 2
• A nonreactive result indicates no HCV antibody detected and no further testing is needed in immunocompetent persons without recent exposure 2
• A reactive result requires immediate reflex to HCV RNA testing 1

Step 2: HCV RNA Testing (Reflex)

• Perform qualitative or quantitative HCV RNA nucleic acid testing (NAT) on the same blood sample if antibody is reactive 2, 1
• Positive HCV RNA = current active infection requiring treatment evaluation 1
• Negative HCV RNA = past resolved infection or false positive antibody 1

Special Testing Scenarios

Recent Exposure (Within 6 Months)

• If initial antibody test is negative but exposure occurred within the past 6 months, perform direct HCV RNA testing or repeat antibody testing ≥6 months after exposure 1
• Antibody production may be delayed 8-9 weeks after exposure 2

Immunocompromised Patients

• Consider direct HCV RNA testing as antibody production may be delayed or inadequate 1
• This includes patients with HIV/AIDS, those on hemodialysis, or receiving immunosuppressive therapy 2

Patients at Risk for Reinfection

• Use HCV RNA testing rather than antibody testing, as antibodies remain positive after prior clearance 1
• Annual HCV RNA testing is recommended for persons who inject drugs and HIV-positive men who have unprotected sex with men 2

Pre-Treatment Laboratory Evaluation

Once active HCV infection is confirmed (positive HCV RNA), obtain the following before initiating therapy:

Baseline Virologic Testing

• Quantitative HCV RNA viral load to establish baseline 2, 1
• HCV genotype determination (though less critical with pangenotypic direct-acting antivirals) 1

Baseline Laboratory Panel

• Complete blood count (CBC) 2
• Comprehensive metabolic panel including creatinine and calculated GFR 2
• Hepatic function panel (ALT, AST, bilirubin, alkaline phosphatase, albumin) 2
• International normalized ratio (INR) 2
• Hepatitis B surface antigen and HIV antibody (due to overlapping risk factors and impact on prognosis) 2

Fibrosis Assessment

• Determine degree of liver fibrosis using non-invasive testing or liver biopsy to assess urgency of treatment 3
• Patients with advanced fibrosis (Metavir F3-F4) require more intensive monitoring 2

Monitoring During Antiviral Therapy

Laboratory Monitoring Schedule

• At week 4 of treatment: CBC, creatinine, calculated GFR, hepatic function panel, and quantitative HCV RNA 2
• Additional monitoring as clinically indicated for drug-related toxicity 2
• Thyroid-stimulating hormone every 12 weeks if interferon-based therapy is used 2

Safety Monitoring for Hepatotoxicity

Discontinue therapy immediately if: 2

• 10-fold increase in ALT at week 4, OR
• Any ALT increase <10-fold at week 4 accompanied by weakness, nausea, vomiting, jaundice, increased bilirubin, alkaline phosphatase, or INR

Efficacy Monitoring

• If HCV RNA is detectable at week 4, repeat testing at week 6 2
• Discontinue treatment if HCV RNA increases >10-fold (>1 log10 IU/mL) at week 6 or thereafter 2

Post-Treatment Testing

Sustained Virologic Response (SVR) Assessment

• Quantitative HCV RNA at 12 weeks after completion of therapy (SVR12) is the primary endpoint 2
• Optional: HCV RNA at end of treatment and/or 24 weeks post-treatment 2
• Undetectable HCV RNA at ≥12 weeks post-treatment = virologic cure (>99% durable) 2

Long-Term Follow-Up After SVR

Patients WITHOUT Advanced Fibrosis (F0-F2)

• No additional HCV-specific follow-up required 2

Patients WITH Advanced Fibrosis or Cirrhosis (F3-F4)

• Hepatocellular carcinoma surveillance with abdominal ultrasound every 6 months indefinitely 2
• Endoscopic surveillance for esophageal varices if cirrhosis is present 2
• Hepatic function panel, CBC, and INR every 6-12 months 2

Testing for Reinfection

• Only perform HCV RNA testing (not antibody) if ongoing risk factors or unexplained hepatic dysfunction 2
• Do not routinely monitor for recurrence in patients on immunosuppressive therapy 2

Common Pitfalls to Avoid

• Never rely solely on antibody testing - this misses the distinction between active and resolved infection 1
• Do not use antibody testing to detect reinfection - antibodies remain positive after clearance; use HCV RNA instead 1
• Ensure reflex RNA testing is implemented - requiring separate visits for confirmatory testing leads to loss to follow-up 1
• Do not use ALT levels to stage disease - ALT fluctuates and does not correlate with fibrosis stage 2
• Remember that immunocompromised patients may have false-negative antibody tests - consider direct RNA testing 1