What is a Hepatitis C (HCV) panel?

What is a Hepatitis C Panel?

A hepatitis C panel is a two-step diagnostic testing sequence that begins with HCV antibody testing followed by reflex HCV RNA testing to distinguish between current active infection, past resolved infection, and false-positive results. 1, 2, 3

Components of the Hepatitis C Panel

Step 1: HCV Antibody Testing

• Anti-HCV antibody testing is the first-line diagnostic test using either enzyme immunoassay (EIA) in the laboratory or rapid diagnostic tests (RDTs) at point-of-care 4
• The antibody test detects exposure to HCV but cannot distinguish between active infection, resolved infection, or false-positive results 4, 2
• Anti-HCV antibodies are detectable in the vast majority of patients with HCV infection, though results may be negative in early acute hepatitis C (within first 6 months) and in profoundly immunosuppressed patients 4
• Third-generation anti-HCV tests contain antigens from the HCV core, nonstructural 3, nonstructural 4, and nonstructural 5 genes, providing improved sensitivity 5

Step 2: HCV RNA Testing (Reflex Testing)

• If anti-HCV antibodies are detected, HCV RNA must be determined by a sensitive molecular method with a lower limit of detection <15 IU/ml 4
• HCV RNA testing is the definitive method to confirm current active infection versus past resolved infection 4, 2
• The most efficient approach uses reflex testing where the same blood sample collected for antibody testing is automatically tested for HCV RNA if the antibody result is positive 2, 3
• Quantitative HCV RNA assays using polymerase chain reaction (PCR) or branched-chain DNA technology detect viral load, with optimal sensitivity of <100 copies per milliliter 5

Interpretation of Results

Anti-HCV Positive + HCV RNA Detected

• Indicates current chronic HCV infection requiring treatment evaluation 1, 2
• Following spontaneous or treatment-induced viral clearance, anti-HCV antibodies persist in the absence of HCV RNA but may decline over time 4

Anti-HCV Positive + HCV RNA Not Detected

• Indicates either past resolved infection or false-positive antibody result 2, 3
• To differentiate between these possibilities, testing with a second different HCV antibody assay can be considered 4, 2
• Patients should be informed they do not have current infection but are not protected from reinfection 3

Anti-HCV Negative

• No evidence of current or past HCV infection 2, 3
• Exception: In cases of suspected acute hepatitis C (within 6 months of exposure) or immunocompromised patients, HCV RNA testing should be part of the initial evaluation even with negative antibody results 4, 3

Additional Testing Components

HCV Genotype Testing

• Determines which of the six major HCV genotypes (1-6) is present 4
• Historically important for treatment selection, though becoming less necessary with pangenotypic direct-acting antiviral regimens 3
• HCV genotype determination may be considered when it would alter treatment recommendations 3

Quantitative Viral Load

• Quantitative HCV RNA testing is recommended prior to initiating antiviral therapy to establish baseline viral load 1, 3
• Used to monitor treatment response and confirm sustained virological response (SVR) at 12 weeks after treatment completion 4, 6

Special Testing Scenarios

Recent Exposure (Within 6 Months)

• Direct HCV RNA testing or follow-up HCV antibody testing ≥6 months after exposure is recommended for those with initial negative antibody tests 4, 2, 3
• HCV RNA can be detected during the acute phase although brief interludes of undetectable HCV RNA may occur 4

Immunocompromised Patients

• HCV RNA testing should be considered even with negative antibody results, as antibody production may be delayed or absent 2, 3
• Anti-HCV antibodies may be undetectable in profoundly immunosuppressed patients despite active infection 4

Risk of Reinfection

• For patients at risk for reinfection after previous clearance, HCV RNA testing is recommended since antibody tests will remain positive 2, 3
• This applies to people who inject drugs or others with ongoing risk factors 3

Common Pitfalls to Avoid

• Relying solely on antibody testing without confirmatory HCV RNA testing leads to misdiagnosis of active versus resolved infection 2, 3
• Missing the diagnosis in immunocompromised patients who may not mount adequate antibody responses requires direct RNA testing 4, 3
• Failing to implement reflex RNA testing results in patients being lost to follow-up between antibody and confirmatory testing 3
• Not recognizing that positive antibody with negative RNA indicates past resolved infection, not current infection requiring treatment 2
• Overlooking reinfection by using only antibody testing in previously infected patients will miss new active infections 3