What are the next tests for a patient with a positive Hepatitis B surface antigen (HBsAg) result?

Next Steps After Positive HBsAg

Complete the hepatitis B serologic panel immediately with anti-HBc (total and IgM), anti-HBs, HBeAg, and anti-HBe to determine whether this represents acute versus chronic infection and the phase of disease. 1, 2

Initial Serologic Workup

• Order anti-HBc IgM to distinguish acute infection (IgM positive) from chronic infection (IgM negative or low-level positive) 1
• Measure anti-HBs to identify the rare scenario of resolving infection where HBsAg may still be transiently positive 1, 3
• Test HBeAg and anti-HBe to determine viral replication status, as HBeAg positivity indicates high-level replication while anti-HBe positivity suggests lower replication 1, 2
• Confirm HBsAg positivity at a second time point (ideally 6 months later) to establish chronicity, as chronic hepatitis B is defined by HBsAg persistence beyond 6 months 1

Virologic Assessment

• Obtain quantitative HBV DNA using a sensitive real-time PCR assay to assess viral replication level, which is critical for treatment decisions 1, 2
  • Levels ≥2,000 IU/mL in HBeAg-negative patients or ≥20,000 IU/mL in HBeAg-positive patients indicate active disease requiring treatment consideration 2
  • HBV DNA helps distinguish inactive carriers (DNA <2,000 IU/mL) from those with active hepatitis 1

Biochemical and Liver Function Tests

• Measure ALT and AST to assess hepatocellular injury and disease activity 1, 4
• Check liver synthetic function with albumin, bilirubin, and prothrombin time/INR to identify any hepatic decompensation 4
• Obtain complete blood count to screen for thrombocytopenia or other cytopenias suggesting cirrhosis 1

Mandatory Coinfection Screening

• Test for HIV in all HBsAg-positive patients, as HIV/HBV coinfection accelerates liver disease and fundamentally changes treatment approach 1, 2
• Screen for hepatitis C with anti-HCV antibody, as coinfection significantly worsens prognosis 2, 5
• Check anti-HDV (hepatitis D antibody) if available, as HDV superinfection causes more severe liver disease 2
• Test for anti-HAV IgG to determine if hepatitis A vaccination is needed, since acute HAV in chronic HBV patients increases mortality 5.6- to 29-fold 1, 3

Imaging and Fibrosis Assessment

• Perform abdominal ultrasound to assess liver echotexture, exclude focal lesions, and screen for signs of cirrhosis (nodular surface, splenomegaly, portal hypertension) 4
• Consider non-invasive fibrosis assessment with FibroScan or serum fibrosis markers if available, though liver biopsy remains the gold standard when safely feasible 1
• Initiate HCC surveillance with ultrasound and AFP every 6 months if cirrhosis is present or suspected 2

Clinical History Priorities

• Document risk factors including country of origin (endemic areas), family history of HBV or HCC, injection drug use, sexual exposures, and prior blood transfusions 1
• Assess alcohol consumption as abstinence is mandatory in chronic HBV to prevent accelerated fibrosis 1
• Review medication history for immunosuppressive therapy or chemotherapy, as HBV reactivation risk is substantial, particularly with anti-CD20 agents like rituximab 1
• Evaluate for symptoms of decompensation (ascites, encephalopathy, variceal bleeding) or constitutional symptoms 1

Common Pitfalls to Avoid

• Do not assume isolated HBsAg positivity means chronic infection without confirming persistence beyond 6 months, as acute infection also presents with positive HBsAg 1
• Do not rely on HBV DNA alone for diagnosis of chronic infection, as levels fluctuate and are not reliable markers of chronicity 1
• Do not skip HIV testing even in patients without obvious risk factors, as this is a mandatory screening test that changes management 1, 2
• Beware of the "window period" in acute infection where HBsAg may be negative but IgM anti-HBc is positive 3, 2
• Remember that false-negative HBsAg can occur in chronic liver disease, so if clinical suspicion is high, proceed with HBV DNA testing 1

Monitoring Schedule After Initial Workup

• Repeat ALT every 3-6 months even in patients not requiring immediate treatment, as disease activity fluctuates 2
• Recheck HBeAg/anti-HBe if initially HBeAg-positive to detect seroconversion, which indicates favorable disease transition 2
• Monitor HBV DNA periodically to detect changes in viral replication status that may warrant treatment initiation 2