Blood Tests for Hepatitis B and C Screening
Hepatitis B Screening Tests
For hepatitis B screening, order three specific serologic tests: Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc) total or IgG, and Hepatitis B surface antibody (anti-HBs). 1 This triple-test approach is recommended by the American Association for the Study of Liver Diseases and aligns with CDC universal screening guidance for all adults aged 18 years and older. 2
Initial Screening Panel
- HBsAg - detects active infection (both acute and chronic) 1
- Anti-HBc (total or IgG) - identifies current or past exposure to hepatitis B 1
- Anti-HBs - indicates immunity from vaccination or resolved infection 1
Follow-Up Testing Based on Initial Results
If HBsAg and/or anti-HBc are positive, proceed with HBV-DNA viral load testing to assess active viral replication. 2 This reflex testing approach is reasonable and efficient for risk stratification, particularly for patients who will undergo immunosuppressive therapy. 2
Interpretation of Results
| Test Results | Clinical Interpretation |
|---|---|
| HBsAg+, anti-HBc+, anti-HBs- | Active chronic HBV infection [1] |
| HBsAg-, anti-HBc+, anti-HBs+ | Resolved HBV infection [1] |
| HBsAg-, anti-HBc+, anti-HBs- | Isolated core antibody (possible occult HBV) [1] |
| HBsAg-, anti-HBc-, anti-HBs+ | Immunity from vaccination [1] |
| HBsAg-, anti-HBc-, anti-HBs- | Susceptible to HBV infection [1] |
Hepatitis C Screening Tests
For hepatitis C screening, order HCV-antibody testing with reflex HCV RNA PCR testing using a single blood draw. 1, 3, 4 This two-step reflex approach is the gold standard recommended by the American Association for the Study of Liver Diseases and eliminates the need for return visits, addressing a major barrier in the HCV care continuum. 3
Initial Screening Strategy
- Step 1: HCV-antibody testing using an FDA-approved enzyme immunoassay or rapid test 3, 4
- Step 2: Automatic reflex to quantitative HCV RNA PCR if antibody is positive 3, 4
This reflex testing requires only a single blood collection and provides definitive diagnosis of active infection without requiring patient return for confirmatory testing. 3
Test Interpretation
- Positive antibody + Positive RNA = Current active HCV infection requiring treatment evaluation 3, 4
- Positive antibody + Negative RNA = Past resolved infection or false positive; patient does not have current infection but is not protected from reinfection 3
- Negative antibody = No evidence of current or past infection (unless recent exposure or immunocompromised) 3
Special Testing Scenarios
For patients with recent exposure (within 6 months) and negative antibody test, order direct HCV RNA testing or repeat antibody testing ≥6 months after exposure, as antibody production may be delayed 8-9 weeks. 3, 4
For immunocompromised patients, consider direct HCV RNA testing rather than antibody testing, as antibody production may be delayed or inadequate. 3, 4
For patients at risk for reinfection (e.g., people who inject drugs), use HCV RNA testing rather than antibody testing, since antibodies remain positive after prior clearance. 3, 4
Who Should Be Screened
Universal one-time screening is recommended for all adults aged 18 years and older for both hepatitis B and C. 1 For hepatitis C specifically, the American Association for the Study of Liver Diseases recommends universal screening for adults aged 18-79 years. 2, 3
Annual testing is specifically recommended for people who inject drugs and men with HIV who have unprotected sex with men. 3
Pre-Treatment Testing for HCV (If Positive)
Before initiating HCV antiviral therapy, obtain:
- Quantitative HCV RNA viral load to establish baseline 3, 4
- HCV genotype (though less critical with pangenotypic direct-acting antivirals) 3, 4
- Complete blood count, comprehensive metabolic panel, hepatic function panel, and INR 4
- HBsAg and anti-HBc - mandatory before starting HCV treatment, as HBV reactivation has been reported in HCV/HBV coinfected patients receiving direct-acting antivirals, with some cases resulting in fulminant hepatitis, hepatic failure, and death 5, 6
Critical Pitfalls to Avoid
Do not order IgM anti-HBc for routine screening - only order when acute hepatitis B is specifically suspected. 1
Do not rely solely on HBsAg for comprehensive HBV screening - you will miss resolved infections and isolated core antibody patterns. 1
Never rely solely on HCV antibody testing without reflex RNA - this misses the critical distinction between active and resolved infection and is the most common screening error. 3, 4
Do not use antibody testing to detect HCV reinfection - antibodies remain positive after clearance; always use HCV RNA instead. 3, 4
Do not skip HBV testing before initiating HCV treatment - HBV reactivation during HCV direct-acting antiviral therapy can be fatal. 5, 6