Can a patient with a positive Hepatitis A (hepatitis A virus) Immunoglobulin G (IgG) start immunosuppressive therapy?

Immunosuppressive Therapy in Patients with Positive Hepatitis A IgG

A patient with a positive hepatitis A IgG can safely start immunosuppressive therapy as hepatitis A IgG indicates past infection with immunity and does not pose a risk for reactivation during immunosuppression. However, screening for hepatitis B virus (HBV) infection is essential before starting any immunosuppressive therapy.

Understanding Hepatitis A IgG Positivity

• Positive hepatitis A IgG indicates previous infection with hepatitis A virus (HAV) or successful vaccination
• Unlike HBV, hepatitis A does not establish chronic infection or latency in the body
• HAV does not integrate into the host genome and cannot reactivate during immunosuppression
• Hepatitis A IgG provides long-term immunity against future HAV infection 1

Required Screening Before Immunosuppressive Therapy

Before initiating immunosuppressive therapy, comprehensive screening for hepatitis B is mandatory:

• All patients should be tested for HBsAg, anti-HBc IgG, and anti-HBs 2
• This screening is critical as HBV reactivation can occur in both:
  • HBsAg-positive patients (chronic HBV infection)
  • HBsAg-negative/anti-HBc-positive patients (resolved or occult HBV infection)

Risk Assessment for HBV Reactivation

The risk of HBV reactivation depends on:

1. Serological status:

   • High risk: HBsAg-positive patients
   • Moderate risk: HBsAg-negative/anti-HBc-positive patients receiving certain therapies
   • Low risk: HBsAg-negative/anti-HBc-positive patients on low-risk therapies

2. Type of immunosuppressive therapy:

   • High risk (>10%): B-cell depleting agents (rituximab), high-dose corticosteroids (>20mg prednisone daily for ≥4 weeks), anthracyclines, potent TNF-α inhibitors
   • Moderate risk (1-10%): Systemic chemotherapy, less potent TNF-α inhibitors, cytokine inhibitors
   • Low risk (<1%): Traditional immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate), low-dose corticosteroids (<10mg prednisone daily) 2

Management Recommendations

For HBsAg-positive patients:

• Prophylactic antiviral therapy is mandatory regardless of HBV DNA level 2
• Use high-barrier-to-resistance antivirals (entecavir, tenofovir) 2, 3
• Start antivirals 2-4 weeks before immunosuppression when possible 2
• Continue for at least 6-12 months after stopping immunosuppression 2

For HBsAg-negative/anti-HBc-positive patients:

• For high-risk immunosuppressive therapy: Prophylactic antiviral therapy recommended 2
• For moderate-risk therapy: Consider prophylaxis or close monitoring (HBsAg and HBV DNA every 1-3 months) 2
• For low-risk therapy: Monitoring without prophylaxis is generally sufficient 2

Antiviral Selection:

• Preferred agents: Entecavir or tenofovir (high genetic barrier to resistance) 3
• Avoid lamivudine for long-term prophylaxis due to high resistance rates 2

Common Pitfalls to Avoid

1. Failing to screen for HBV before immunosuppression: This is the most critical error and can lead to potentially fatal HBV reactivation 4, 5

2. Confusing hepatitis A immunity with hepatitis B immunity: These are distinct viruses with different implications for immunosuppression

3. Using lamivudine for long-term prophylaxis: High resistance rates (20% at 1 year, 30% at 2 years) make this a poor choice for extended use 2

4. Discontinuing prophylaxis too early: Antiviral therapy should continue for at least 6-12 months after stopping immunosuppression (up to 18-24 months after rituximab) 2

5. Neglecting monitoring: Even with prophylaxis, regular monitoring of liver function and viral markers is essential 2

In conclusion, while hepatitis A IgG positivity does not pose a risk for reactivation during immunosuppression, comprehensive screening for HBV is mandatory before starting immunosuppressive therapy to prevent potentially fatal HBV reactivation.