What is the next step for a patient with a reactive anti-hepatitis B (anti-HBc) core antibody but negative hepatitis B surface antigen (HBsAg) who wants to start Pre-Exposure Prophylaxis (PREP)?

Management of Patient with Reactive Anti-HBc, Negative HBsAg Seeking PrEP

For a patient with reactive anti-hepatitis B core antibody (anti-HBc) but negative hepatitis B surface antigen (HBsAg) who wants to start PrEP, the next step is to test for HBV DNA and anti-HBs levels, then monitor HBsAg, ALT, and HBV DNA every 1-3 months during PrEP therapy without delaying PrEP initiation.

Initial Assessment

• All patients should undergo comprehensive HBV screening with three tests before starting PrEP: HBsAg, anti-HBc (total or IgG), and anti-HBs 1
• The patient's current status (HBsAg-negative, anti-HBc-positive) indicates resolved or occult HBV infection 1
• Baseline HBV DNA testing is essential to determine viral replication status 1

Risk Assessment

• PrEP medications (tenofovir disoproxil fumarate/emtricitabine or tenofovir alafenamide/emtricitabine) have anti-HBV activity and generally pose low risk for HBV reactivation 1
• HBsAg-negative/anti-HBc-positive patients are at lower risk for HBV reactivation compared to HBsAg-positive patients 1
• The presence of anti-HBs provides additional protection against reactivation (4.3% reactivation rate with anti-HBs vs. 14% without) 1, 2

Management Algorithm

1. Baseline Testing:

   • Check HBV DNA level 1
   • Confirm anti-HBs status if not already done 1, 2
   • Assess baseline liver function tests (ALT/AST) 1

2. PrEP Initiation:

   • PrEP can be initiated without delay while awaiting test results 1
   • PrEP medications containing tenofovir have dual activity against HIV and HBV 1

3. Monitoring Plan:

   • Monitor HBsAg, ALT, and HBV DNA every 1-3 months during therapy 1
   • Continue monitoring for at least 6 months after any interruption of PrEP 1

Special Considerations

• If HBV DNA is positive, consult with a hepatologist for possible antiviral treatment 1
• If anti-HBs is negative, the patient is at higher risk for reactivation (14% vs 5% with anti-HBs) and requires closer monitoring 2, 3
• Caution is needed if PrEP is discontinued, as this could potentially lead to HBV reactivation in patients with occult infection 1

Pitfalls to Avoid

• Do not delay PrEP initiation while waiting for HBV test results 1
• Do not rely solely on anti-HBs status to determine management, as reactivation can still occur in anti-HBs positive patients 1, 2
• Avoid using lamivudine for HBV treatment if needed, due to high resistance rates; prefer entecavir or tenofovir 1
• Be aware that HBV reactivation can occur even years after exposure to immunosuppressive therapy 1

Follow-up

• Educate patient about signs and symptoms of hepatitis flare 1
• Ensure continuity of PrEP to prevent both HIV acquisition and potential HBV reactivation 1
• Consider hepatology consultation if there are abnormal liver function tests or detectable HBV DNA 1