What is the recommended screening test for Hepatitis C (HCV) infection?

Recommended Screening Test for Hepatitis C Virus (HCV) Infection

HCV-antibody testing with reflex HCV RNA polymerase chain reaction testing is the recommended screening test for hepatitis C infection. 1

Initial Screening Approach

The optimal screening strategy for HCV follows a two-step process:

• Step 1: HCV-antibody testing using an FDA-approved assay (laboratory-based or point-of-care) should be performed as the initial screening test 1
• Step 2: Reflex HCV RNA PCR testing should automatically follow any positive antibody test to confirm active infection 1

This reflex testing approach is crucial as it:

• Requires only a single blood collection 1
• Eliminates the need for a return visit for confirmatory testing 1
• Addresses a major barrier in the HCV care continuum 1

Special Testing Considerations

Different testing approaches may be needed in specific situations:

• Recent exposure (within 6 months): HCV RNA testing or follow-up HCV-antibody testing ≥6 months after exposure is recommended for those with negative antibody tests 1
• Immunocompromised patients: Consider direct HCV RNA testing as antibody production may be delayed or inadequate 1
• Patients at risk for reinfection: HCV RNA testing is recommended since antibody tests will remain positive after prior clearance 1
• Rural or difficult-to-access populations: Dried blood spot collection can be used for sequential antibody and reflex RNA testing, requiring only a fingerstick rather than venipuncture 1

Test Interpretation

Understanding test results is essential for proper patient management:

• Positive antibody + positive RNA: Current (active) HCV infection requiring evaluation for treatment 1
• Positive antibody + negative RNA: Past resolved infection or false positive; patients should be informed they do not have current infection but are not protected from reinfection 1
• Negative antibody: No evidence of current or past infection (unless recent exposure or immunocompromised) 1

Who Should Be Screened

Current guidelines recommend:

• Universal screening: One-time HCV screening for all adults aged 18-79 years 1, 2
• Risk-based screening: One-time testing for persons <18 years with risk factors 1
• Periodic testing: For those with ongoing risk factors, with frequency determined by individual risk assessment 1
• Annual testing: Specifically recommended for people who inject drugs and men with HIV who have unprotected sex with men 1
• Pregnancy: Testing during each pregnancy 2

Additional Testing After Diagnosis

For patients diagnosed with active HCV infection:

• Quantitative HCV RNA testing: Recommended prior to antiviral therapy to establish baseline viral load 1
• HCV genotype testing: May be considered when it would alter treatment recommendations, though becoming less necessary with pangenotypic direct-acting antiviral regimens 1

Common Pitfalls to Avoid

• Relying solely on antibody testing: This can miss active infection or incorrectly classify resolved infections as current 1
• Missing the diagnosis in high-risk groups: Especially in people who inject drugs or immunocompromised patients 1, 3
• Delayed diagnosis: Failure to implement reflex RNA testing leads to patients being lost to follow-up between antibody and confirmatory testing 1
• Overlooking reinfection: Using only antibody testing in previously infected patients will miss reinfection 1

Early diagnosis through appropriate screening is critical as current direct-acting antiviral treatments can achieve >95% cure rates, significantly improving mortality outcomes and quality of life 4.