Can a patient with a positive Hepatitis B (HBV) core antibody (anti-HBc) but negative Hepatitis B surface antigen (HBsAg) be started on Pre-Exposure Prophylaxis (PrEP)?

PrEP in Patients with Positive Hepatitis B Core Antibody but Negative HBsAg

Patients with positive hepatitis B core antibody (anti-HBc) but negative hepatitis B surface antigen (HBsAg) can safely start PrEP, but should be monitored for potential HBV reactivation during treatment.

Risk Assessment for HBV Reactivation

• Patients who are HBsAg-negative but anti-HBc-positive are considered to have past HBV exposure (resolved infection) 1
• This serologic profile indicates a low risk for HBV reactivation compared to HBsAg-positive patients 1
• The risk of HBV reactivation in anti-HBc-positive/HBsAg-negative individuals is generally <1% in most clinical scenarios 1

Recommendations for PrEP Initiation

• For patients with positive anti-HBc but negative HBsAg, pre-emptive therapy rather than prophylactic antiviral treatment is generally recommended 1
• This approach involves:
  • Baseline testing of HBV DNA levels before starting PrEP 1
  • Regular monitoring of HBsAg and HBV DNA every 1-3 months during PrEP treatment 1
  • Immediate initiation of anti-HBV treatment if HBsAg seroreversion or detectable HBV DNA occurs 1

Monitoring Protocol

• Before starting PrEP:
  • Confirm complete HBV serologic profile (HBsAg, anti-HBc, anti-HBs) 1
  • Test baseline HBV DNA level 1
  • Check liver enzymes (ALT/AST) 2
• During PrEP treatment:
  • Monitor HBsAg, HBV DNA, and ALT every 1-3 months 1
  • Continue monitoring for at least 6-12 months after completion of PrEP if discontinued 1

Special Considerations

• If the patient has additional risk factors for HBV reactivation, such as:
  • Concurrent immunosuppressive therapy 1
  • History of chemotherapy, especially with B-cell depleting agents like rituximab 1
  • Hematologic malignancies 1
• Then prophylactic anti-HBV therapy should be considered before starting PrEP 1

Management of HBV Reactivation

• If HBsAg seroreversion or detectable HBV DNA occurs during monitoring:
  • Immediately start antiviral therapy with high barrier to resistance (entecavir, tenofovir DF, or tenofovir alafenamide) 1
  • Do not delay treatment regardless of ALT levels, as HBsAg seroreversion can lead to severe hepatitis 1
  • Continue anti-HBV treatment for at least 6 months after completion of PrEP 1

Practical Approach

1. Screen all patients for HBsAg, anti-HBc, and anti-HBs before starting PrEP 1
2. For patients with isolated anti-HBc positivity (HBsAg-negative):
   • Test for baseline HBV DNA 1
   • If HBV DNA is undetectable, proceed with PrEP with monitoring 1
   • If HBV DNA is detectable, treat as an HBsAg-positive patient with prophylactic anti-HBV therapy 1
3. Implement regular monitoring schedule (every 1-3 months) for HBsAg, HBV DNA, and liver enzymes 1
4. Be prepared to initiate prompt anti-HBV treatment if reactivation occurs 1

Conclusion

The benefit of PrEP for HIV prevention outweighs the low risk of HBV reactivation in patients with isolated anti-HBc positivity. With appropriate monitoring and readiness to initiate anti-HBV treatment if needed, these patients can safely receive PrEP therapy 1.