What tests should be ordered when a patient tests positive for Hepatitis B surface antigen (HBsAg)?

Initial Tests for Patients with Positive HBsAg

When a patient tests positive for Hepatitis B surface antigen (HBsAg), a comprehensive panel of tests should be ordered including HBeAg/anti-HBe, HBV DNA, complete liver function tests, and screening for coinfections with other viral hepatitis and HIV. 1

Core Initial Evaluation Tests

• Confirmation of HBsAg positivity: A second HBsAg test at a different time point (at least 6 months apart) to confirm chronicity 1
• Complete hepatitis B serologic panel:
  • HBeAg and anti-HBe (to determine replication status and disease phase) 1, 2
  • Anti-HBc total (to differentiate between acute, chronic, or resolved infection) 1
  • Anti-HBs (to assess for partial immunity) 1
• HBV DNA quantification (viral load) to assess level of viral replication 1, 2
• Liver function tests:
  • ALT, AST (to assess liver inflammation) 1
  • Alkaline phosphatase, gamma-glutamyl transpeptidase 1
  • Bilirubin, albumin, prothrombin time (to assess liver synthetic function) 1, 3
• Complete blood count (to assess for thrombocytopenia as a marker of portal hypertension) 1, 2
• Renal function tests: BUN, creatinine (for baseline assessment before potential antiviral therapy) 2

Coinfection Screening

• HIV testing (due to shared transmission routes and impact on management) 1, 2
• Anti-HCV (to rule out HCV coinfection) 1, 2
• Anti-HDV (to rule out hepatitis D coinfection, especially in high-risk patients) 1, 2
• IgG anti-HAV (to assess immunity status to hepatitis A, especially in patients younger than 50 years) 1

Additional Recommended Tests

• Alpha-fetoprotein (AFP) (for HCC screening) 1, 2
• Liver ultrasound (to assess for cirrhosis and exclude focal lesions) 1, 3
• Liver biopsy (optional, to assess degree of necroinflammation and fibrosis when treatment decisions are unclear) 1

Clinical Interpretation of Results

• HBeAg positivity generally indicates high viral replication, while anti-HBe positivity typically indicates lower viral replication 1
• HBeAg-negative, anti-HBe-positive patients with normal ALT and HBV DNA <2,000 IU/mL may be in the inactive carrier state 1
• HBeAg-negative patients with elevated ALT and HBV DNA >2,000 IU/mL likely have HBeAg-negative chronic hepatitis B 1

Common Pitfalls to Avoid

• Relying solely on HBsAg without confirming chronicity: A single positive HBsAg test cannot differentiate between acute and chronic infection; confirmation at 6 months is essential 1
• Missing coinfections: Failure to test for HIV, HCV, and HDV can lead to missed opportunities for appropriate management 1
• Overlooking hepatitis A immunity: Patients with chronic HBV who lack immunity to HAV should receive HAV vaccination due to increased risk of severe disease if coinfected 1
• Incomplete evaluation of liver status: Both biochemical and imaging studies are needed to properly stage liver disease 1, 3

Follow-up Management

• All HBsAg-positive patients should receive education about their condition 1
• Contact tracing and vaccination of susceptible contacts should be initiated 1
• Counseling regarding alcohol abstinence is essential 1
• Patients should be evaluated for treatment eligibility based on HBV DNA levels, ALT levels, and liver disease severity 1, 2

By following this comprehensive testing approach, clinicians can accurately determine the phase of HBV infection, assess liver damage, screen for coinfections, and make appropriate treatment decisions to reduce morbidity and mortality associated with chronic hepatitis B.