What is the next step in management for a patient who is Hepatitis B surface antigen (HBsAg) reactive?

Management of HBsAg Reactive Patient

Immediately order HBV DNA quantification, ALT/AST, complete hepatic function panel (albumin, bilirubin, PT/INR), and HBeAg status to determine disease phase and treatment eligibility. 1, 2

Initial Diagnostic Workup

The presence of HBsAg indicates either acute or chronic HBV infection, with chronicity defined by HBsAg persistence beyond 6 months. 1, 3 Your immediate next steps must stratify disease activity and determine treatment urgency:

Essential Laboratory Tests

• HBV DNA by PCR: This is the single most critical test to distinguish inactive carrier state (HBV DNA <2,000 IU/mL) from active chronic hepatitis B (HBV DNA ≥2,000 IU/mL). 1, 2
• ALT and AST levels: Elevated transaminases indicate hepatic inflammation requiring treatment consideration. 1, 2
• Complete hepatic function panel: Including albumin, bilirubin, alkaline phosphatase, GGT, and prothrombin time to assess synthetic function and identify decompensation. 2
• HBeAg and anti-HBe: Determines if patient has HBeAg-positive or HBeAg-negative chronic hepatitis B. 1, 2
• Complete blood count and creatinine: Baseline assessment before potential antiviral therapy. 2

Mandatory Coinfection Screening

• Anti-HCV, anti-HDV, anti-HIV: Coinfections dramatically alter prognosis and management. 2
• Anti-HAV (IgG): If negative, hepatitis A vaccination is mandatory as coinfection increases mortality 5.6- to 29-fold. 1

Imaging and Fibrosis Assessment

• Abdominal ultrasound: Screen for cirrhosis, portal hypertension, and hepatocellular carcinoma. 4
• Consider non-invasive fibrosis assessment: Liver stiffness measurement (FibroScan) or serum fibrosis markers, particularly if HBV DNA ≥2,000 IU/mL. 1

Disease Classification and Treatment Decisions

If HBV DNA ≥2,000 IU/mL AND Elevated ALT (>ULN)

Initiate antiviral therapy immediately with first-line agents: entecavir 0.5 mg daily OR tenofovir (TDF or TAF). 1, 2 These agents have high barriers to resistance and are strongly preferred over lamivudine, which has resistance rates up to 70% at 5 years. 1

The 2025 guidelines from the American Association for the Study of Liver Diseases represent a major shift from older thresholds (HBV DNA >20,000 IU/mL and ALT >2× ULN), now recommending treatment at lower viral loads and ALT elevations to prevent disease progression. 1

If HBV DNA ≥2,000 IU/mL AND Normal ALT

Consider treatment if any of the following are present: 1

• Age >40 years with family history of HCC
• Evidence of at least moderate fibrosis (liver stiffness ≥9 kPa with normal ALT or ≥12 kPa with any ALT)
• HBeAg-positive patients over age 30 with persistently normal ALT and high HBV DNA

If HBV DNA <2,000 IU/mL AND Normal ALT (Inactive Carrier)

Monitor without immediate treatment, but surveillance is mandatory: 5, 2

• ALT every 3-4 months for the first year, then every 6 months lifelong
• HBV DNA measurement every 6-12 months
• This phase can reactivate to active disease, requiring vigilant monitoring

If Any Cirrhosis is Present

Treat immediately with entecavir or tenofovir regardless of HBV DNA level or ALT, even if HBV DNA is barely detectable. 1 Simultaneously evaluate for liver transplantation if decompensated. 1

Critical Special Circumstances

Planned Immunosuppression or Chemotherapy

This is a common pitfall where HBV reactivation can cause acute liver failure and death. 5

For HBsAg-positive patients receiving any of the following, start antiviral prophylaxis 2-4 weeks before therapy: 5

• High-risk agents (rituximab, anthracyclines, high-dose steroids >20 mg prednisone daily >4 weeks, TNF-α inhibitors like infliximab): Reactivation risk 12-50%
• Moderate-risk agents (most systemic chemotherapy, tyrosine kinase inhibitors, moderate-dose steroids): Reactivation risk 1-10%

Continue prophylaxis through treatment and for at least 12 months after the last dose (extend to 24 months for rituximab). 5

The exception is hormonal therapy alone (without steroids), where close monitoring may suffice. 5

Pregnancy

If pregnant or planning pregnancy with HBV DNA >200,000 IU/mL, start tenofovir DF at 24-32 weeks gestation to prevent mother-to-child transmission. 1 Breastfeeding is not contraindicated. 1

Hepatocellular Carcinoma Surveillance

Initiate ultrasound screening every 6 months immediately if any of the following apply: 1, 2

• Asian men >40 years or Asian women >50 years
• Any patient with cirrhosis
• Family history of HCC
• Age >40 with persistent ALT elevation
• African/African American patients >20 years

This is non-negotiable regardless of treatment status, as HCC risk persists even with viral suppression.

Treatment Monitoring Protocol

For patients on antiviral therapy: 1, 2

• HBV DNA every 3 months until undetectable, then every 6 months
• ALT/AST every 3-6 months
• Renal function every 6 months (tenofovir can cause nephrotoxicity)
• Annual quantitative HBsAg to assess for functional cure (HBsAg loss)
• Continue HCC surveillance as above

Treatment is typically indefinite for HBeAg-negative chronic hepatitis B. 1, 2 Stopping therapy risks severe reactivation and should only be considered in highly selected cases with prolonged viral suppression and close monitoring capability.

Common Pitfalls to Avoid

• Do not use lamivudine as first-line therapy due to high resistance rates. 1
• Do not delay antiviral prophylaxis in patients about to start immunosuppression—this must be initiated 2-4 weeks before chemotherapy/immunosuppression. 5
• Do not assume normal ALT means no treatment needed—patients with significant fibrosis or cirrhosis require treatment regardless of ALT. 1
• Do not stop monitoring inactive carriers—they can reactivate to active disease and require lifelong surveillance. 5, 2
• Do not forget to vaccinate against hepatitis A if seronegative, as coinfection dramatically increases mortality. 1