Adoptive donor immunity protects against resolved hepatitis B virus reactivation after allogeneic haematopoietic stem cell transplantation in the world's largest retrospective cohort study

Abstract

Summary Reactivation of hepatitis B virus (HBV) by reverse seroconversion (HBV‐RS) after allogeneic haematopoietic stem cell transplantation (allo‐HSCT) can occur in patients with resolved HBV infection (rHBV, defined as negative HBV surface antigen [HBsAg] and positive HBV core antibody), and may cause fatal hepatitis. To explore the risk factors, we retrospectively identified 817 consecutive patients who underwent allo‐HSCT from 2005 to 2016 in this largest single centre cohort from National Taiwan Univerisity Hospital. Transplants using donors or recipients positive for HBsAg or HBV DNA were excluded, leaving 445 rHBV patients for analysis. The 3‐ and 5‐year cumulative incidence of HBV‐RS after allo‐HSCT was 8·7% and 10·5%, respectively, at a median 16 months after allo‐HSCT. All had concurrent HBV reactivation. HBV flares developed in 19% of HBV‐RS cases, but none experienced hepatic failure. Neither did it impact non‐relapse mortality or overall survival. Multivariate analysis revealed that patients with donor lacking hepatitis B surface antibody and extensive chronic graft‐versus‐host disease (cGVHD) have the highest risk for HBV‐RS, with 5‐year incidence of 24·2%. In conclusion, adoptive immunity transfer from the donor seems to have protective effects against HBV‐RS, which may alter future donor selection algorithms, and combined with extensive cGVHD provides a good target for risk‐adaptive HBV prophylaxis.

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

“…In an Italian study group, the risk of HBV reactivation was decreased in the case of an HBV-immune/exposed donor, and the donor immunity was independently associated with a decreased risk of HBV reactivation [14]. In a large retrospective cohort study evaluating 445 allo-HSCT patients with resolved HBV infections, patients with a donor lacking antiHBs was identified as an independent risk factor for HBV reverse seroconversion [35]. These findings imply a mechanism of adaptive immune transfer from the donor and may provide evidence for future donor selection.…”

“…No impact on non-relapse mortality or survival was identified. Patients with a donor lacking antiHBs and the presence of extensive chronic GVHD were identified as independent risk factors for HBV reverse seroconversion, with a 5-year incidence of 24.2% [35]. A close follow-up protocol with periodic serum HBV DNA level monitoring is needed, especially if such patients could not receive antiviral prophylaxis.…”

HBV Reactivation in Patients Undergoing Hematopoietic Stem Cell Transplantation: A Narrative Review

“…Another clinically relevant issue on adaptive immunity in allo-HSCT comes from studies showing that recipient-derived humoral immunity seems to have a protective role against HBVr after allo-HSCT [53]. However, the loss of previous HBV immunity might be inevitable as a result of the loss of the recipient’s immune cells in combination with the prolonged inadequate T-cell-dependent B-cell responses [54].…”

“…CD52 is expressed on most lymphocytes, monocytes, macrophages, and epithelial cells. Several cases of HBVr after alemtuzumab therapy have been reported ([53], and reviewed in [59]).…”

“…Patients undergoing allo-HSCT requiring more intense and prolonged immunosuppression have a higher risk of HBVr than auto-HSCT recipients [65]. Patients with GVHD (acute and/or chronic) are at risk for HBVr since they are further immunocompromised by the routine use of prophylactic cyclosporine and methotrexate or mycophenolate mofetil for the prevention of GVHD [53,60]. When GVHD is diagnosed, treatment with high doses of steroids or antithymocyte globulin or both further suppress the host immunity [58].…”