Which laboratory tests should be ordered to screen for hepatitis B and hepatitis C in a patient with mildly elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) while on apixaban?

Laboratory Screening for Hepatitis B and C

For screening hepatitis B and C in a patient with mildly elevated ALT/AST, order: HBsAg (hepatitis B surface antigen), anti-HCV (hepatitis C antibody), and if anti-HCV is positive, follow with HCV RNA PCR.

Initial Screening Tests

Hepatitis B Screening

• HBsAg (Hepatitis B surface antigen) - This is the primary screening test for active hepatitis B infection 1, 2
• If HBsAg is positive, proceed to confirmatory testing with:
  • HBeAg/anti-HBe to assess viral replication status 3
  • Quantitative HBV DNA (using real-time PCR assay) to measure viral load 3, 4
  • IgM anti-HBc to distinguish acute from chronic infection 5, 1

Hepatitis C Screening

• Anti-HCV antibody - Initial screening test for hepatitis C exposure 4, 2
• If anti-HCV is positive:
  • HCV RNA by PCR (nucleic acid test) to confirm active infection 6, 1
  • Anti-HCV antibody alone cannot distinguish active from resolved infection

Context for Your Patient on Apixaban

The apixaban drug label notes that transaminase elevations can occur as adverse reactions, though this is uncommon 7. However, do not assume the elevated ALT/AST is from apixaban without excluding viral hepatitis first, as hepatitis B and C are common causes of mildly elevated transaminases 8, 9.

Complete Initial Evaluation Panel

Beyond viral hepatitis screening, the comprehensive workup for mildly elevated transaminases should include 2, 9, 10:

• Complete blood count with platelets
• Hepatic panel: albumin, bilirubin, alkaline phosphatase, prothrombin time
• Metabolic syndrome assessment: fasting glucose/A1C, lipid panel (to evaluate for nonalcoholic fatty liver disease)
• Iron studies: serum iron, total iron-binding capacity, ferritin (to screen for hemochromatosis)
• Anti-HAV IgG if patient is under 50 years old 4

Important Caveats

The ALT/AST elevation pattern matters: Hepatocellular injury (disproportionate ALT/AST elevation compared to alkaline phosphatase) suggests viral hepatitis, fatty liver disease, or drug-induced injury, whereas cholestatic patterns suggest biliary obstruction 8, 10.

Timing is critical: If HBsAg is positive on initial testing, repeat testing after 6 months is necessary to confirm chronic infection (versus transient acute infection) 5, 1. For hepatitis C, anti-HCV can remain positive after spontaneous clearance, which is why HCV RNA confirmation is mandatory 6.

Normal ALT does not exclude significant liver disease: Up to 25-30% of chronic hepatitis B patients with normal ALT can have significant fibrosis on biopsy 11. Recent guidelines suggest lowering ALT treatment thresholds to 35 U/L for men and 25 U/L for women to better identify patients needing treatment 11.