What are the next steps in managing a patient with a reactive Hepatitis B Surface Antigen (HBsAg) result?

Management of Reactive Hepatitis B Surface Antigen (HBsAg)

A reactive HBsAg result indicates active hepatitis B virus infection and requires immediate completion of a full serologic panel (anti-HBc, HBeAg, anti-HBe), quantitative HBV DNA testing, liver function tests (ALT, AST, bilirubin, albumin), and liver imaging to determine disease activity, replication status, and need for antiviral therapy. 1, 2, 3

Immediate Diagnostic Workup

Complete the following tests without delay:

• Serologic markers: Anti-HBc (total or IgM), HBeAg, anti-HBe to determine infection phase and chronicity 1, 3
• Quantitative HBV DNA: Essential to assess viral replication and guide treatment decisions 1, 2, 4
• Liver function tests: ALT, AST, bilirubin, albumin, prothrombin time to evaluate hepatic injury and synthetic function 3, 5
• Abdominal ultrasound: To assess for cirrhosis, exclude focal liver lesions, and screen for hepatocellular carcinoma 3

If HBsAg persists beyond 6 months, this confirms chronic HBV infection rather than acute infection. 4

Determine Infection Phase and Treatment Candidacy

For HBeAg-Positive Patients:

• Treat if: HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal (ULN) 1
• Consider liver biopsy if: Age >40 years with borderline ALT levels or HBV DNA in the "gray zone" (2,000-20,000 IU/mL), as moderate/severe inflammation or fibrosis warrants treatment 1
• Monitor without treatment if: In immune tolerance phase (high HBV DNA, normal ALT, age <40) unless patient is >40 years old, as persistently high HBV DNA increases risk of cirrhosis and HCC 1

For HBeAg-Negative Patients:

• Treat if: HBV DNA >20,000 IU/mL AND ALT >2× ULN 1
• Consider liver biopsy if: HBV DNA 2,000-20,000 IU/mL with any ALT elevation, particularly if age >40 years 1
• Monitor without treatment if: HBV DNA <2,000 IU/mL with persistently normal ALT (confirmed on 3+ evaluations over time), indicating inactive carrier state 1

Special Clinical Scenarios Requiring Immediate Action

Patients Requiring Immunosuppression or Chemotherapy:

All HBsAg-positive patients must receive prophylactic antiviral therapy before starting cancer chemotherapy, immunosuppressive therapy (including rituximab or anti-TNF agents), or transplantation. 1, 6

• Preferred antivirals: Tenofovir or entecavir (avoid lamivudine due to high resistance rates) 1, 7
• Duration: Continue prophylaxis through treatment and for 12 months after completing immunosuppressive therapy 1
• Monitoring: Check HBV DNA and ALT monthly during therapy and every 3 months for 12 months after stopping 1

Failure to provide prophylaxis can result in severe hepatitis flares, liver failure, and death during or after immunosuppression. 1, 6

Pregnant Women with High Viral Load:

• If HBV DNA >7-8 log IU/mL (>1,000-10,000 IU/mL), consider prophylactic antiviral therapy in the third trimester to prevent perinatal transmission 1
• Safe options include lamivudine, telbivudine, or tenofovir 1

Contact Tracing and Prevention

Identify and test all household contacts, sexual partners, and needle-sharing contacts for HBsAg, anti-HBc, and anti-HBs. 1

• Susceptible contacts (all markers negative): Vaccinate immediately with first dose while awaiting serologic results 1
• Unvaccinated contacts: Complete 3-dose hepatitis B vaccine series 1

Counseling and Transmission Prevention

Inform the patient that HBsAg-positive status means they can transmit HBV to others. 8, 7

• Do not share: Needles, razors, toothbrushes, or any items that may contact blood 1, 8
• Sexual transmission: Use barrier protection; partners should be vaccinated 1
• Blood/organ donation: Patient cannot donate blood, organs, or tissues 1

Ongoing Monitoring for Untreated Patients

If treatment is not initiated, monitor every 3-6 months with:

• ALT and AST: To detect disease flares 1, 3
• HBV DNA: To assess changes in viral replication 1, 4
• HCC surveillance: Ultrasound every 6 months for patients with cirrhosis, family history of HCC, or age >40 years with ongoing inflammation 1

Common Pitfalls to Avoid

• Never assume inactive disease based on a single normal ALT; confirm with serial testing over 3+ evaluations 1
• Do not delay prophylaxis in patients about to start immunosuppression—initiate antivirals before the first dose of chemotherapy or immunosuppressive agents 1
• Avoid lamivudine monoprophylaxis due to high resistance rates; use tenofovir or entecavir instead 1
• Do not overlook occult HBV infection: Even HBsAg-negative, anti-HBc-positive patients can reactivate with immunosuppression and require monitoring or prophylaxis 1, 6