In an adult with chemotherapy‑induced neutropenia who has acute hepatitis B infection, what is the recommended antiviral management (drug choice, dose, duration, monitoring) and how should the neutropenia be treated?

Management of Acute Hepatitis B in a Neutropenic Patient

Immediate Antiviral Management

Start entecavir or tenofovir (TDF/TAF) immediately without waiting for HBV DNA results, as acute hepatitis B in an immunocompromised neutropenic patient represents a severe clinical scenario requiring urgent intervention. 1, 2

Drug Selection and Dosing

• Entecavir or tenofovir are the only acceptable first-line agents due to their high potency and high barrier to resistance in immunocompromised patients 3
• Never use lamivudine in this setting—resistance rates reach 70% over 5 years, and immunosuppressed patients require prolonged therapy 1, 4
• Standard dosing: Entecavir 0.5 mg daily OR tenofovir disoproxil fumarate 300 mg daily OR tenofovir alafenamide 25 mg daily 3

Duration of Antiviral Therapy

The treatment duration differs fundamentally from immunocompetent acute hepatitis B:

• Continue antiviral therapy throughout the entire period of neutropenia and immunosuppression 3, 1
• Extend for minimum 12 months after completion of all chemotherapy (not just after neutrophil recovery) 3
• If rituximab or anti-CD20 therapy was involved, extend to 18 months post-chemotherapy 3, 1
• For stem cell transplant recipients, consider lifelong therapy until HBsAg clearance with anti-HBs seroconversion occurs 3

Management of Neutropenia

Growth Factor Support

• Use filgrastim (G-CSF) for severe neutropenia (ANC <500 cells/μL) to accelerate immune recovery, which is critical for HBV control 5, 6
• G-CSF can be administered safely alongside entecavir or tenofovir without drug interactions 5, 6
• Monitor neutrophil counts 2-3 times weekly during acute phase 6

Infection Prevention

• Implement neutropenic precautions: avoid fresh fruits/vegetables, no live plants in room, strict hand hygiene 5
• Consider prophylactic antibiotics if ANC <500 cells/μL and fever develops 6
• Do not delay HBV antiviral therapy while managing neutropenia—both conditions require simultaneous urgent treatment 1, 2

Monitoring Protocol

Baseline Assessment

• HBV DNA level, HBsAg, anti-HBc, anti-HBs 3, 1
• Complete blood count with differential 5
• Comprehensive metabolic panel including ALT, AST, bilirubin, INR 2, 4
• Check INR immediately—if ≥1.5, this signals severe acute hepatitis requiring liver transplant evaluation 2, 4

Ongoing Surveillance

• Weekly monitoring during acute phase: INR, ALT, AST, bilirubin, complete blood count 2, 4
• HBV DNA every 1-3 months during antiviral therapy 3, 1
• Monthly ALT for first 3 months after stopping antivirals, then every 3 months for 12 months to detect late reactivation 3, 1

Critical Clinical Decision Points

When to Escalate Care

• INR >1.5 = immediate hepatology consultation and transplant evaluation 2, 4
• Persistent jaundice or symptoms >4 weeks = protracted course requiring intensified monitoring 2, 4
• Any signs of hepatic encephalopathy = acute liver failure, transfer to transplant center 3, 2

Distinguishing Acute HBV from Reactivation

This distinction may be difficult but does not change management—both require immediate nucleos(t)ide analogue therapy with entecavir or tenofovir 3, 2

Common Pitfalls to Avoid

• Never adopt a "wait and see" approach citing the 95% spontaneous recovery rate in immunocompetent patients—this does NOT apply to neutropenic/immunosuppressed patients 2, 4
• Do not stop antivirals at 3 months even if HBV DNA becomes undetectable—premature discontinuation causes reactivation in immunosuppressed patients 3
• Do not use interferon in acute hepatitis B or in any patient with neutropenia—it worsens cytopenias and is contraindicated in decompensated liver disease 3, 2
• Do not delay chemotherapy for HBV screening results, but start antivirals immediately once positive serology is identified 3, 1

Coordination of Care

• Involve hepatology or infectious disease specialist experienced in HBV management for all immunocompromised patients with acute hepatitis B 3, 1
• Coordinate with oncology/hematology regarding chemotherapy modifications if severe hepatotoxicity develops 3, 7
• Consider early transplant hepatology consultation if any signs of hepatic decompensation emerge 3, 2