Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor

Abstract

The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.

Update on prevention, diagnosis, and treatment of chronic hepatitis B

“…The most commonly studied and recommended duration of prophylactic antiviral therapy is 6‐12 months after discontinuation of anticancer therapy or immunosuppression. Reactivation beyond 12 months has been reported, so further monitoring should be considered, particularly for patients who received anti‐CD20 antibody therapy . Much less is known about the optimal duration of prophylaxis in patients receiving chronic immunosuppression, for example, transplantation and biological therapy …”

“…Reactivation beyond 12 months has been reported, so further monitoring should be considered, particularly for patients who received anti-CD20 antibody therapy. (208)(209)(210) Much less is known about the optimal duration of prophylaxis in patients receiving chronic immunosuppression, for example, transplantation and biological therapy. (182,(211)(212)(213)(214) Guidance Statements for Patients Undergoing Immunosuppressive and Cytotoxic Therapy 1.…”

Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases

“…98,[107][108][109] The antiviral prophylaxis is recommended to be administered 6 to 12 months after discontinuation of immunosuppression, 107 as HBV reactivation beyond 12 months reported, particularly in patients who received rituximab (anti-CD20 antibody). [110][111][112]…”

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

“…LAM may be used safely in this setting although few cases of HBV exacerbation due to LAM resistance have been reported. [210][211][212] Prophylaxis with ETV or TDF or TAF can be also considered in HBsAg-negative, anti-HBc positive patients receiving highly immunosuppressive regimens of extended duration. 213,214 In HBsAg-negative, anti-HBc positive subjects with moderate (\10%) or low (\1%) risk of HBV reactivation, pre-emptive therapy, not prophylaxis, is generally recommended.…”