What are the usual tests ordered for screening hepatitis C (HCV) infection?

Hepatitis C Screening Tests

The usual screening for hepatitis C infection begins with an HCV antibody test, followed by reflex HCV RNA testing if the antibody is reactive. 1

Initial Screening Test

Begin with HCV antibody testing using an FDA-approved assay (either laboratory-based enzyme immunoassay or rapid test like OraQuick HCV Rapid Antibody Test). 2

• A nonreactive (negative) HCV antibody result indicates no HCV antibody detected and requires no further testing in most cases 2
• A reactive (positive) HCV antibody result indicates one of three possibilities: current infection, past resolved infection, or false positivity 2

Special Consideration for Recent Exposure

• If recent HCV exposure within the past 6 months is suspected, proceed directly to HCV RNA testing even if antibody is negative, as antibodies may not yet have developed 2, 1
• For immunocompromised patients, consider HCV RNA testing regardless of antibody status, as antibody response may be impaired 2, 1

Confirmatory Testing

All reactive HCV antibody results must be followed by HCV RNA testing using nucleic acid testing (NAT) to confirm current infection. 2, 1

• HCV RNA detected = current active infection requiring treatment 2, 1
• HCV RNA not detected = either past resolved infection or false-positive antibody result 2, 1

Optimal Testing Workflow

The most efficient approach uses reflex testing from a single blood draw: 1

• Option 1: The same venipuncture blood sample used for HCV antibody testing is automatically reflexed to HCV RNA testing if antibody is reactive 2
• Option 2: Collect two tubes at initial venipuncture—one for antibody testing and one held for HCV RNA testing if needed 2

Alternative Confirmatory Marker

HCV core antigen can be used as a surrogate marker for HCV RNA when molecular testing is unavailable or unaffordable, though it is slightly less sensitive than HCV RNA assays. 2

Common Pitfalls to Avoid

• Never rely solely on HCV antibody testing without confirmatory HCV RNA—a positive antibody alone cannot distinguish current from past infection 1
• Do not assume positive antibody equals active infection—approximately 15-45% of persons with reactive antibodies have spontaneously cleared the virus and are HCV RNA negative 1
• Do not miss acute infection in high-risk exposures—antibodies may take 6-12 weeks to develop, so direct HCV RNA testing is needed if recent exposure is suspected 2, 1
• For persons previously treated or with spontaneous clearance, antibodies remain positive indefinitely, so only HCV RNA testing can detect reinfection 1

Summary Algorithm

1. Order HCV antibody test (laboratory EIA or rapid test) 2
2. If nonreactive: No further testing unless recent exposure suspected 2
3. If reactive: Automatically proceed to HCV RNA testing 2, 1
4. If HCV RNA positive: Current infection—link to care and treatment 2, 1
5. If HCV RNA negative: Past resolved infection or false positive—no treatment needed 2, 1