Is the Hepatitis B (HBV) vaccine recommended for a patient on steroids and planned systemic therapy, and what precautions should be taken?

Hepatitis B Vaccination During Steroids and Planned Systemic Therapy

Administer the hepatitis B vaccine immediately to all HBsAg-negative patients before starting immunosuppressive therapy, as vaccination is safe and effective even during steroid use, though response rates may be reduced with high-dose steroids (≥20 mg prednisone daily for ≥2 weeks) or B-cell depleting agents.

Immediate Screening Requirements

Before initiating any systemic therapy, all patients must undergo hepatitis B screening 1, 2:

• HBsAg (hepatitis B surface antigen) - determines active infection 1, 2
• Anti-HBc (hepatitis B core antibody) - indicates prior exposure 1
• Anti-HBs (hepatitis B surface antibody) - confirms immunity 2, 3
• HBV DNA by PCR if HBsAg-negative but anti-HBc-positive to detect occult infection 1, 3

Vaccination Strategy Based on Serologic Status

If HBsAg-Negative and Anti-HBs-Negative (No Immunity)

Vaccinate immediately before starting immunosuppression 1:

• Use recombinant hepatitis B vaccine administered intramuscularly in the deltoid muscle (not gluteal, which has significantly lower response rates) 1, 4, 5
• Standard 3-dose schedule: 0,1, and 6 months 1
• For immunocompromised patients or those on hemodialysis: use higher doses (40 μg for Engerix-B or Recombivax HB) 1
• Alternative 2-dose schedule with Heplisav-B (20 μg at 0 and 1 month) is approved for adults ≥18 years 1

If HBsAg-Positive (Active Chronic Infection)

Do NOT vaccinate - initiate antiviral prophylaxis instead 1, 2, 6:

• Start entecavir or tenofovir (high barrier to resistance agents) 2-4 weeks before beginning immunosuppressive therapy 1, 3
• Continue prophylaxis throughout treatment and for 12 months after completion (extend to 24 months for rituximab) 1, 3
• This prevents hepatitis B reactivation, which carries a 12-50% risk with high-risk immunosuppressive agents 1, 3

If Anti-HBc-Positive but HBsAg-Negative (Resolved Infection)

Prophylactic antiviral therapy is preferred over vaccination for patients receiving high-risk immunosuppression 1, 3:

• High-risk agents include: rituximab, anthracyclines, high-dose steroids (≥20 mg prednisone daily for ≥2 weeks), anti-TNF agents 1
• Use entecavir or tenofovir starting before immunosuppression 1, 3
• If anti-HBs is present at high levels (>100 IU/L), may consider monitoring HBV DNA monthly instead of prophylaxis 3

Impact of Immunosuppression on Vaccine Response

Steroids

• Low-dose steroids (<10 mg/day prednisone or <0.5-2.0 mg/kg/day in children): vaccination is safe with good serological responses 1
• High-dose steroids (≥20 mg/day prednisone for ≥2 weeks): significantly reduced antibody responses to vaccination 1
• Critical pitfall: A fatal case report demonstrates that steroids can reactivate hepatitis B in carriers, causing fulminant liver failure 7

Disease-Modifying Antirheumatic Drugs (DMARDs)

• Methotrexate: vaccination is safe; response rates are adequate at doses ≤20 mg/week 1
• Azathioprine/6-MP: vaccination is safe at standard doses 1

Biologic Agents

• Anti-TNF agents (infliximab, adalimumab, etanercept): vaccination is safe; most patients achieve protective antibody levels, though geometric mean concentrations may be lower 1
• Rituximab (B-cell depleting): markedly blunted immune response when vaccine given within 6 months of treatment 1
• Tocilizumab, ustekinumab: vaccination appears safe without disease flares 1

Post-Vaccination Monitoring

Measure anti-HBs antibody levels 1-2 months after completing the vaccine series in the following high-risk groups 1:

• Patients on high-dose steroids (≥20 mg prednisone daily for ≥2 weeks) 1
• Patients receiving rituximab or other B-cell depleting agents 1
• Patients on anti-TNF therapy (can be considered) 1
• Hemodialysis patients 1, 8

Response Criteria and Management

• Protective response: anti-HBs ≥10 IU/L 1, 8
• Non-responders (anti-HBs <10 IU/L): revaccinate with a second 3-dose series 1
• Consider booster doses if antibody levels fall below 10 IU/L, particularly in patients with ongoing immunosuppression 1

Optimal Timing Strategy

The best approach is to vaccinate BEFORE starting immunosuppression whenever possible 1:

1. Ideally: Complete the entire 3-dose series before initiating immunosuppressive therapy 1
2. If urgent therapy needed: Give at least the first dose before starting treatment, then complete the series during therapy 1
3. For rituximab specifically: Vaccinate at least 2-4 weeks before the first dose, as response is severely impaired if given within 6 months after rituximab 1

Critical Pitfalls to Avoid

• Never delay vaccination waiting for "optimal" immune status - vaccinate immediately even if response may be suboptimal, as some protection is better than none 1, 9
• Never use gluteal injection site - this results in significantly lower seroconversion rates (78% vs 97% for deltoid) 4, 5
• Never assume immunity without testing in patients who will receive immunosuppression 1
• Never use lamivudine for prophylaxis due to high resistance rates (70% at 5 years) 1, 6
• Do not withhold vaccination based on low CD4 count or high viral load in HIV patients - vaccine response occurs at all CD4 levels, and HIV viral load is a better predictor than CD4 count 9

Additional Preventive Measures

• Vaccinate against hepatitis A if anti-HAV negative, as coinfection increases mortality 5.6- to 29-fold 1, 2, 3
• Counsel on alcohol abstinence to prevent additional liver injury 3
• Screen household and sexual contacts for hepatitis B and vaccinate if seronegative 1