I have a reactive hepatitis B surface antigen (HBsAg) result; what does this indicate and what are the next steps in evaluation and management?

Reactive HBsAg: Diagnosis and Management

What a Reactive HBsAg Means

A reactive (positive) hepatitis B surface antigen (HBsAg) indicates active hepatitis B virus infection—either acute or chronic—and requires immediate further evaluation with additional serologic markers and HBV DNA quantification to determine disease phase and guide management. 1

HBsAg is the hallmark serologic marker of HBV infection and is the first marker to appear during acute infection. 2 Persistence of HBsAg for more than 6 months defines chronic HBV infection. 1

Essential Next Steps in Evaluation

Complete the Serologic Panel

You must obtain the following tests immediately to characterize your infection status: 1

• Hepatitis B e antigen (HBeAg) and anti-HBe antibody
• Hepatitis B core antibody (anti-HBc), both IgM and total
• Hepatitis B surface antibody (anti-HBs)
• Quantitative HBV DNA level (viral load)
• Liver enzymes (ALT/AST) 1

Additional Baseline Testing

• Complete blood count, comprehensive metabolic panel 1
• Assessment of liver fibrosis using noninvasive methods (FibroScan, FIB-4, APRI) or liver biopsy if indicated 1
• Hepatitis C, hepatitis D (if HBV DNA >2000 IU/mL), and HIV screening 1
• Alpha-fetoprotein (AFP) and liver imaging if cirrhosis is suspected 1

Determining Your Disease Phase

The combination of these results will classify you into one of several phases, which determines whether you need treatment: 1

Immune-Tolerant Phase (Generally No Treatment)

• HBeAg positive
• HBV DNA typically >1 million IU/mL
• Normal or minimally elevated ALT
• Minimal liver inflammation/fibrosis 1

Immune-Active Phase (Treatment Indicated)

• HBeAg-positive: HBV DNA >20,000 IU/mL with elevated ALT 1
• HBeAg-negative: HBV DNA >2000 IU/mL with elevated ALT 1
• Moderate to severe liver inflammation or any degree of fibrosis 1

Inactive Carrier State (Monitor, Don't Treat)

• HBeAg negative, anti-HBe positive
• HBV DNA <2000 IU/mL
• Persistently normal ALT (requires 1 year of monitoring every 3-4 months to confirm) 1
• Minimal liver inflammation 1

Treatment Indications

You should start antiviral therapy if you meet any of these criteria: 1

• HBV DNA >20,000 IU/mL (HBeAg-positive) or >2000 IU/mL (HBeAg-negative) AND elevated ALT
• Any detectable HBV DNA with evidence of significant fibrosis (≥F2) or cirrhosis
• Evidence of active liver inflammation on biopsy regardless of HBV DNA level
• Family history of hepatocellular carcinoma or cirrhosis 1

Critical Considerations for Immunosuppression

If you are planning to undergo or are currently receiving immunosuppressive therapy, you require immediate antiviral prophylaxis regardless of your HBV DNA level or ALT. 1

High-Risk Immunosuppressive Therapies Requiring Prophylaxis

• B-cell depleting agents (rituximab, ofatumumab, alemtuzumab)
• High-dose corticosteroids
• Anthracyclines (doxorubicin, epirubicin)
• TNF-α inhibitors (infliximab, adalimumab, certolizumab, golimumab) 1

Prophylaxis should begin 2-4 weeks before starting immunosuppression and continue for at least 6-12 months after the last dose (up to 2 years for rituximab). 1

Monitoring Requirements

If You Are an Inactive Carrier

• ALT every 6 months after the first year of confirmation
• HBV DNA periodically (at least annually)
• Closer monitoring if HBV DNA >2000 IU/mL 1

If You Have Chronic Active Hepatitis

• More frequent monitoring based on treatment status and disease severity
• HCC surveillance with ultrasound and AFP every 6 months if cirrhotic or at high risk 1

Transmission Risk and Counseling

You are infectious and can transmit HBV to others through blood, sexual contact, and perinatally. 1

• Household contacts and sexual partners should be tested and vaccinated if susceptible 1
• Practice safe sex and avoid sharing personal items that may have blood contact 1
• Inform healthcare providers of your HBV status before any procedures 1

Common Pitfalls to Avoid

• Do not assume you are an inactive carrier without at least 1 year of monitoring showing persistently normal ALT and low HBV DNA, as HBeAg-negative chronic hepatitis can have fluctuating patterns. 1
• Do not delay antiviral prophylaxis if immunosuppression is planned, even if you appear to be an inactive carrier—reactivation can be severe and life-threatening. 1
• Do not rely on a single ALT or HBV DNA measurement to make treatment decisions in the absence of cirrhosis. 1