What labs are needed to work up and rule out hepatitis B and C in a patient?

Laboratory Workup to Rule Out Hepatitis B and C

To screen for hepatitis B and C, order HBsAg and anti-HBc for hepatitis B, and anti-HCV antibody with reflex HCV RNA for hepatitis C. 1, 2

Hepatitis B Screening Panel

Initial Serologic Tests

• Order HBsAg (Hepatitis B surface antigen) as the primary screening test for current HBV infection 1, 2
• Order total anti-HBc (Hepatitis B core antibody) to detect both recent and past infections—this is total antibody, not IgM 1, 2
• Consider anti-HBs (Hepatitis B surface antibody) to determine immunity status from vaccination or prior infection 1, 2

Follow-up Testing if HBsAg is Positive

• Order IgM anti-HBc to distinguish acute from chronic infection—IgM is typically only positive in acute hepatitis B 1, 2
• Order HBeAg and anti-HBe to determine viral replication status 2
• Order quantitative HBV DNA to assess viral load and replication activity 2

Hepatitis C Screening Panel

Initial Serologic Test

• Order anti-HCV antibody as the primary screening test 3, 1
• Reflex to HCV RNA testing (nucleic acid test) if anti-HCV is positive to confirm current infection 3, 1

Interpretation Algorithm

• Anti-HCV positive + HCV RNA positive = current active infection 1
• Anti-HCV positive + HCV RNA negative = either false positive or resolved past infection 3
  • If HCV RNA is negative, repeat testing with a different antibody platform to distinguish false positive from cleared infection 3
  • Consider repeat HCV RNA testing if recent exposure (within 6 months) or clinical suspicion remains high 3

Additional Baseline Laboratory Tests

Once infection is confirmed, assess liver disease severity:

• Liver function tests: ALT, AST, bilirubin, albumin, alkaline phosphatase 3, 2
• Coagulation studies: Prothrombin time/INR 3, 2
• Complete blood count with platelets 3, 2

Coinfection Screening

• Test for HIV in all patients with confirmed HBV or HCV, especially in high-risk populations 3, 2
• Test for HBV in HCV-positive patients (HBsAg and anti-HBc) due to overlapping risk factors and risk of HBV reactivation during HCV treatment 3, 4, 5
• Test for HCV in HBV-positive patients (anti-HCV) 2
• Test for anti-HAV IgG to determine hepatitis A immunity status—vaccinate if negative 3, 2
• Consider anti-HDV testing in patients with injection drug use history or from endemic areas 2

Special Considerations and Common Pitfalls

Window Period and Recent Exposure

• For suspected recent exposure (within 6 months), order HBV DNA or HCV RNA directly as antibodies may not have developed yet 3, 1
• During the acute HBV "window period," both HBsAg and anti-HBs may be negative—IgM anti-HBc will be the only positive marker 2

Immunocompromised Patients

• Consider direct viral testing (HBV DNA or HCV RNA) in immunocompromised patients as antibody production may be impaired 1
• Seroconversion may be delayed or absent in immunosuppressed individuals 3

Occult Infections

• Isolated anti-HBc positivity requires careful interpretation—may indicate occult HBV infection and warrants HBV DNA testing 1, 2
• Relying solely on HBsAg may miss occult HBV infections, particularly in immunosuppressed patients 1

False Positives

• Anti-HCV false positives can occur, especially in low-prevalence populations—always confirm with HCV RNA testing 3, 1
• Testing only for anti-HCV without confirmatory HCV RNA cannot distinguish current infection from resolved past infection 1

HBeAg-Negative Chronic Hepatitis B

• Do not assume low HBV DNA means inactive disease—HBeAg-negative chronic hepatitis B can have lower viral loads but still cause progressive liver damage 2