Post-Transplant Hepatitis B Prophylaxis with Entecavir
For post-transplant hepatitis B prophylaxis, entecavir should be used in combination with hepatitis B immunoglobulin (HBIG) for high-risk patients, while entecavir monotherapy can be considered for low-risk patients after an initial course of combination therapy. 1
Liver Transplantation Prophylaxis Regimen
Standard Approach
- The current standard treatment for prevention of HBV recurrence after liver transplantation is a combination of nucleos(t)ide analogues (NAs) and HBIG, which reduces post-transplant HBV reinfection rate to less than 5% 1
- Entecavir is one of the preferred antivirals due to its high potency and low rate of drug resistance 1
Risk-Stratified Approach
- High-risk patients (HBV DNA positive at transplantation, HDV coinfection, or poor adherence to NA therapy) should receive lifelong combination of HBIG and entecavir 1
- Low-risk patients (HBV DNA negative at transplantation) can receive a short course of HBIG followed by entecavir monotherapy 1
- Entecavir has shown excellent efficacy in preventing HBV recurrence with the highest probability (31%) as the best prophylactic option compared to other regimens 2
Duration of Therapy
- For high-risk patients, lifelong prophylaxis with entecavir is recommended 1
- For low-risk patients, after HBIG discontinuation, indefinite entecavir monotherapy is recommended 3, 4
- Studies have shown that maintenance therapy with entecavir after discontinuation of HBIG prophylaxis is safe and effective, with a low rate of serological recurrence 3
Special Considerations
Renal and Bone Health
- In patients with or at risk for renal and/or bone disease, entecavir is preferred over tenofovir DF 1
- Tenofovir AF is an alternative option in post-transplant patients with renal or bone concerns 1
Donor Considerations
- For HBsAg-negative patients receiving anti-HBc-positive liver grafts, prophylactic antiviral therapy with entecavir should be initiated immediately after surgery 1
- The risk of HBV reactivation varies depending on recipient's immunization status against HBV, with rates ranging from 1.4% to 47.8% without prophylaxis 1
Hematopoietic Stem Cell Transplantation (HSCT)
- All HBsAg-positive or HBV DNA-positive HSCT recipients should receive prophylactic entecavir at the time of transplantation 1
- Prophylactic antiviral therapy should be maintained for at least 12 months after HSCT 1
- HBsAg-negative, HBV DNA undetectable, but anti-HBc-positive HSCT recipients should also start prophylactic entecavir at the time of transplantation 1
Monitoring
- Regular monitoring of HBV serum markers (HBsAg, anti-HBs) and HBV DNA levels is essential 4
- Monitor renal function periodically in all patients on long-term entecavir therapy 1
- For patients who discontinue HBIG, more vigilant monitoring for HBV recurrence is recommended during the first year after discontinuation 3
Pitfalls and Caveats
- Lamivudine is associated with a higher risk of viral resistance and should be avoided for long-term prophylaxis 1
- HBV reactivation can occur late (up to 5-7 years) after transplantation, necessitating long-term prophylaxis 1
- Patients who received B-cell depleting agents are at risk for delayed HBV reactivation and require extended prophylaxis 1
- Entecavir has shown superior efficacy compared to lamivudine in preventing HBV reactivation in the setting of immunosuppression 1, 2