Hepatitis B Virus Infection in Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Considering a steady increase in the number of allogeneic hematopoietic stem cell transplantations (allo-HSCT) worldwide and the significant proportion of the world’s population that has been exposed to hepatitis B virus (HBV) infection, HBV reactivation following allo-HSCT remains an important issue for post-transplant morbidity and mortality. Antiviral prophylaxis can reduce HBV replication, severity of HBV-related hepatitis, and mortality; therefore, identification of patients at risk is crucial. It is recommended that all recipients and donors should be screened for active or prior HBV infection, including HBsAg, antiHBc, and antiHBs. Adoptive immunity transfer from the donor seems to have protective effects against HBV reactivation. Antiviral prophylaxis should be initiated in all HBsAg-positive patients. HBsAg-negative, antiHBc-positive patients remain at risk; therefore, antiviral prophylaxis should be considered if baseline serum HBV DNA is detectable. In HBsAg-negative, antiHBc-positive patients without detectable HBV DNA, close monitoring of viral load with an on-demand therapy is necessary. Entecavir or tenofovir rather than lamivudine are more appropriate for the emergence of lamivudine resistance. The treatment duration remains unclear, with 6- to 12-month therapy after cessation of immunosuppressive therapy commonly recommended. Here we review the updated evidence and recent recommendations regarding HBV reactivation in patients undergoing allo-HSCT for individualized therapy.

KASL clinical practice guidelines for management of chronic hepatitis B

“…In another retrospective study with median follow-up of 21 months, hepatitis B reactivation occurred in four of 96 patients who received prophylactic antiviral therapy for 7 months and in 8 of 219 patients who did not receive prophylactic antiviral therapy [ 408 , 409 ]. According to observational studies, in HBsAg-negative and anti-HBc-positive allogeneic HSCT recipients, the 5-year cumulative incidence of hepatitis B reactivation is frequent (10.5–43.0%), so it is reasonable to commence prophylactic antiviral agents [ 410 ]. Various global guidelines recommend maintaining prophylactic antiviral treatment until 6–18 months after completion of HSCT; however, there is no unified consensus [ 144 , 151 , 368 , 411 - 413 ].…”

“…Various global guidelines recommend maintaining prophylactic antiviral treatment until 6–18 months after completion of HSCT; however, there is no unified consensus [ 144 , 151 , 368 , 411 - 413 ]. According to a recent study, hepatitis B reactivation was continuously reported up to 5–7 years after HSCT [ 410 , 414 ]. Therefore, it might be safe to maintain prophylactic antiviral therapy for a long time after the completion of HSCT, and further studies on the timing of discontinuation of prophylactic antiviral therapy are needed.…”

Chronic Hepatitis B Infection: New Approaches towards Cure

“…The need for LAI treatments for chronic diseases has continued to grow due to improved safety, tolerability, and efficacy. LAI treatment may be considered for preventing HBV reactivations in patients undergoing immunosuppressive therapies or even hepatitis C treatment since HBV rebounds have been reported in these settings (especially in HBsAg+ but also in HBsAg-neg/anti-HBc+ individuals) [ 104 , 105 , 106 ]. The use of ultra-long-acting antivirals for the prevention of certain viral illnesses, halting either contagions or reactivations under immunosuppression would fill an immediate need in providing protection when classic vaccines do not exist, responses are suboptimal, escape mutants emerge or immunity wanes [ 107 ].…”

An ultralong-acting tenofovir ProTide nanoformulation achieves monthslong HBV suppression

“…ULA formulations can also serve to improve patient compliance, as was observed for people living with HIV ( 17 ). Similarly, maternal-fetal transmission would be reduced by ULA formulations ( 18 ), along with transmission and reactivation for patients on immunosuppressive therapy ( 19 ).…”