What laboratory tests should I order to screen for hepatitis B (HBV) and hepatitis C (HCV) in a patient with an unknown history of hepatitis?

Laboratory Testing for Hepatitis B and C Screening

For patients with unknown history of hepatitis, the recommended screening tests include HBsAg, anti-HBc, and anti-HCV, followed by confirmatory testing with HBV DNA and HCV RNA when initial tests are positive.

Hepatitis B Screening Algorithm

Initial Testing

• Order Hepatitis B surface antigen (HBsAg) as the primary screening test for current HBV infection 1
• Order total (not IgM) anti-HBc (Hepatitis B core antibody) to detect both recent and past infections 1
• Consider testing for anti-HBs (Hepatitis B surface antibody) to determine immunity status 1

Interpretation of HBV Screening Results

• HBsAg positive: Indicates current acute or chronic HBV infection 1
  • Follow up with HBeAg, anti-HBe, and HBV DNA quantification to determine replication status 1
  • Test for IgM anti-HBc to distinguish between acute and chronic infection (IgM anti-HBc is usually only detected in acute hepatitis B) 1
• HBsAg negative, anti-HBc positive, anti-HBs positive: Indicates past HBV infection with recovery 1
• HBsAg negative, anti-HBc positive, anti-HBs negative: May indicate:
  • "Window period" of acute infection (if IgM anti-HBc positive) 1
  • Past infection with waning anti-HBs 1
  • Occult HBV infection (consider HBV DNA testing) 1
• HBsAg negative, anti-HBc negative, anti-HBs positive: Indicates immunity from vaccination 1

Hepatitis C Screening Algorithm

Initial Testing

• Order anti-HCV antibody test as the primary screening test 1
  • Either laboratory-based enzyme immunoassay or rapid antibody test can be used 1

Follow-up Testing

• If anti-HCV is positive, reflexively test for HCV RNA using nucleic acid testing (NAT) to confirm current infection 1
  • Ideally, use the same blood sample for reflex testing to avoid additional venipuncture 1

Interpretation of HCV Screening Results

• Anti-HCV negative: No HCV antibody detected, indicates no infection (unless recent exposure) 1
• Anti-HCV positive, HCV RNA positive: Indicates current HCV infection 1
• Anti-HCV positive, HCV RNA negative: Indicates either:
  • Past, resolved HCV infection 1
  • False positive anti-HCV result (consider supplemental antibody testing with a different assay) 1

Special Considerations

• For suspected recent exposure to HBV or HCV (within past 6 months), nucleic acid testing (HBV DNA or HCV RNA) is recommended as antibodies may not have developed 1
• For immunocompromised patients, consider direct viral testing (HBV DNA or HCV RNA) as antibody production may be impaired 1
• Consider testing for coinfections, as HBV-HCV coinfection significantly increases the risk of hepatocellular carcinoma compared to monoinfection 2
• Liver function tests (ALT, AST, bilirubin, albumin, prothrombin time) should be ordered to assess liver disease severity 1

Common Pitfalls to Avoid

• Relying solely on HBsAg for HBV screening may miss occult HBV infections, especially in HIV-positive patients 1
• Testing only for anti-HCV without confirmatory HCV RNA testing cannot distinguish between current infection and resolved past infection 1
• Isolated anti-HBc positivity requires careful interpretation and may need HBV DNA testing to rule out occult infection 1
• False positive anti-HCV results can occur, especially in low-prevalence populations, necessitating confirmatory testing 1

Remember that patients with positive results will need appropriate counseling about their infection status, risk of transmission, and potential need for treatment evaluation 1.