Outcomes of cessation of the administration of nucleos(t)ide analogues on HBV reactivation after allogeneic hematopoietic stem cell transplantation: A nationwide retrospective study

Monitoring of HBV-DNA and HBV-DNA-guided preemptive therapy using nucleos(t)ide analogues (NAs) are recommended for preventing the development of hepatitis due to HBV reactivation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in recipients with resolved HBV infection. However, little is known about the appropriate duration of NA treatment and the outcomes of NAs cessation on recurrence of HBV reactivation. To clarify the consequences of NAs cessation in recipients with resolved HBV infection who experienced HBV reactivation following allo-HSCT. We retrospectively reviewed the clinical records of recipients with resolved HBV infection (HBsAg-negative, anti-HBc-positive) before allo-HSCT who had been diagnosed as having HBV reactivation (HBsAg-positive and/or HBV-DNA detectable) after allo-HSCT during the period from January 2010 to December 2020. A total of 72 patients from 16 institutes were registered (median age of the patients, 60 years; age range, 27-73 years; 42 males and 30 females). Initial HBV reactivation was observed on day 10 to day 3034 (median, 513 days) after allo-HSCT. Anti-HBs were lost in more than 80% of the patients at the time of HBV reactivation. All 72 patients received preemptive NAs and no fatal HBV reactivation-related hepatitis was observed. There was continuous detection of HBV-DNA without hepatitis in 5 patients during the follow-up period. Administration of NAs was discontinued in 24 (33%) of 72 patients by each physician's decision. Second HBV reactivation occurred in 11 (46%) of the 24 patients in whom administration of NAs was discontinued. Duration of NA treatment were not significantly different between patients with or without second HBV reactivation. The frequency of further HBV reactivation tended to be lower in patients with anti-HBs titer of more than 10 mIU/mL at the time of NA cessation. Multiple reactivation of HBV after NA discontinuation was common in patients with HBV reactivation who received allo-HSCT despite the long duration of NA. Careful monitoring of HBV-DNA is important even after the discontinuation of NA in the case with HBV reactivation after allo-HSCT because multiple reactivations could occur. Active immunization by HB vaccine might be effective for suppressing further HBV reactivation after cessation of NAs.