What is the management plan for a patient who is Hepatitis B surface antigen (HBsAg) reactive and anti-Hepatitis B surface antibody (anti-HBs) non-reactive?

Management of HBsAg Reactive, Anti-HBs Non-Reactive Patient

This patient has chronic hepatitis B infection and requires immediate comprehensive evaluation to determine disease activity and treatment eligibility. 1

Immediate Diagnostic Workup Required

Obtain these tests immediately to guide management decisions:

• Quantitative HBV DNA by PCR - This is the single most critical test to distinguish active disease from inactive carrier state and determine treatment eligibility 2, 3, 4
• HBeAg and anti-HBe status - Essential for classifying infection phase (HBeAg-positive vs HBeAg-negative chronic hepatitis B) 1, 4
• Liver enzymes (ALT/AST) - Elevated transaminases indicate hepatic inflammation requiring treatment 1, 2, 4
• Complete metabolic panel - Including albumin, bilirubin, prothrombin time/INR to assess liver synthetic function 4
• Complete blood count - To evaluate for cytopenias suggesting advanced disease 4
• Coinfection screening - Test for anti-HCV, anti-HDV (if injection drug use history), and anti-HIV as these alter management and prognosis 1, 2, 4

Treatment Decision Algorithm

If HBV DNA ≥2,000 IU/mL AND ALT >2× Upper Limit Normal:

• Initiate antiviral therapy immediately with first-line agents: entecavir 0.5 mg daily OR tenofovir (disoproxil fumarate or alafenamide) due to high barrier to resistance 1, 2, 5
• Do not delay treatment for liver biopsy in this scenario 1

If HBV DNA ≥20,000 IU/mL AND ALT elevated (any degree):

• Start treatment immediately regardless of histology 1, 2

If HBV DNA ≥2,000 IU/mL with normal or minimally elevated ALT:

• Assess liver fibrosis using transient elastography (FibroScan) or other non-invasive markers 1, 2
• Treat if liver stiffness ≥9 kPa (with normal ALT) or ≥12 kPa (with ALT <5× ULN) 1, 2
• Treat if age >30 years with persistently elevated HBV DNA, as prolonged immune tolerance increases cirrhosis and HCC risk 2, 3

If cirrhosis is present:

• Treat immediately with any detectable HBV DNA, regardless of ALT levels 1, 4
• Use entecavir 1 mg daily OR tenofovir for decompensated cirrhosis 1, 5

If HBV DNA <2,000 IU/mL with normal ALT (inactive carrier):

• Monitor without immediate treatment - Check HBV DNA and ALT every 3 months for first year, then every 6 months 1, 4

Special Circumstances Requiring Immediate Prophylaxis

If patient is receiving or planning immunosuppressive therapy or chemotherapy:

• All HBsAg-positive patients require prophylactic antiviral therapy regardless of HBV DNA levels 1
• Start antiviral prophylaxis 2-4 weeks before initiating immunosuppression to prevent HBV reactivation, which occurs in 12-50% of untreated patients receiving high-risk agents like rituximab 2, 3, 6
• High-risk immunosuppression (>10% reactivation risk): B-cell depleting agents (rituximab, ofatumumab), anthracyclines, or moderate-to-high dose corticosteroids (≥10 mg prednisone daily for ≥4 weeks) 1
• Continue prophylaxis through treatment and for 12 months after cessation (24 months for rituximab-based regimens) 1

Hepatocellular Carcinoma Surveillance

Initiate ultrasound screening every 6 months immediately for all high-risk patients: 2, 3

• Asian men >40 years or Asian women >50 years 2
• Any patient with cirrhosis 2, 3
• Family history of HCC 2
• Age >40 years with persistent ALT elevation 2
• Continue HCC surveillance indefinitely, even if HBV DNA becomes undetectable on treatment 3

Treatment Monitoring Protocol

For patients initiated on antiviral therapy: 2, 3, 4

• HBV DNA every 3 months until undetectable, then every 6 months 2, 3, 4
• ALT/AST every 3-6 months 2, 3, 4
• Annual quantitative HBsAg testing to assess for potential functional cure (HBsAg loss) 2, 3
• Renal function monitoring if on tenofovir 2

Additional Preventive Measures

• Vaccinate against hepatitis A if anti-HAV negative, as coinfection increases mortality 5.6- to 29-fold 2, 4
• Counsel on complete alcohol abstinence as even limited consumption worsens outcomes 2, 4
• HIV antibody testing should be offered before initiating entecavir therapy 5

Critical Pitfalls to Avoid

• Never use lamivudine as first-line therapy - resistance rates reach 70% at 5 years 2
• Do not treat based solely on HBV DNA or ALT in isolation - both parameters must be considered together with disease phase and fibrosis stage 2, 3
• Do not delay treatment in cirrhotic patients with any detectable HBV DNA 1
• Monitor closely for several months after discontinuing antiviral therapy as severe acute exacerbations can occur 5
• Entecavir is not recommended for HIV/HBV coinfected patients not receiving HAART due to potential HIV resistance development 5

Duration of Therapy

• Long-term, potentially indefinite treatment is typically required for HBeAg-negative chronic hepatitis B 1, 4, 7
• HBsAg loss (functional cure) is the optimal endpoint but is rarely achieved with current therapies 1, 7
• The optimal duration of treatment and relationship to long-term outcomes such as cirrhosis and HCC are unknown 5