Changes of Hepatitis B Immune Status after Allogeneic Hematopoietic Stem Cell Transplantation in HBsAg Negative/Anti-Hbc Positive Patients: A Single Center Observational Study

BACKGROUD:

Low levels or lack of antibodies to the hepatitis B surface antigen (anti-HBsAg, respectively) have been associated with an increased risk of developing an hepatitis B virus (HBV) response in patients with resolved HBV infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Levels of HB core antibodies (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection.

AIMS:

This study aims to determine whether different changes in anti-HBc and anti-HBs levels during allo-HSCT can predict the impact of HBV on the survival of patients who underwent allo-HSCT.

METHODS:

This prospective study enrolled 141 patients who underwent allo-HSCT at the Union Medical College Hospital of Fujian Medical University between 2013 and 2016. The cohort included 65 patients with acute myeloid leukemia, 25 with acute lymphoblastic leukemia, 7 with chronic myeloid leukemia, 15 with aplastic anemia, 5 with lymphoma, and 8 with myelodysplastic syndrome. Based on HBsAg and anti-HBc results, patients were classified as HBsAg-positive (n=16), HBsAg-negative/anti-HBc-positive (n=81), and HBsAg-negative/anti-HBc-negative (n=44). Hepatitis B serological markers (ELISA) and HBV DNA (PCR) were assayed before and every two weeks after HSCT. After transplant, patients received antiviral treatment with a nucleoside analog entecavir given before the transplantation. Antiviral therapy was continued for 1 year after stopping immunosuppressive therapy after transplantation. Death, overall survival (OS), incidence of graft-versus-host disease (GVHD), and drug-induced liver injury were compared among the three groups.

RESULTS:

The three groups were well matched demographically. All patients achieved successful engraftment within one month post-transplant. There was no difference in time to leukocyte and platelet engraftment in the three groups. Comparing OS between the three groups, the two-year OS was 64.3% vs 53.5% vs 52.4%, respectively, with no significant difference (p=0.866). After allo-HSCT, 22/81 (27.1%) subjects in the HBsAg-negative/anti-HBc-positive group exhibited loss of anti-HBc at the median time 6 months (3-21m). The incidence of acute GVHD (46.9 % versus 40 %, P =0.163) was similar in the loss anti-HBc group (n=22) versus no-loss anti-HBc group (n=59). With a median follow-up time of 588 days (range: 46-1582 days), the incidence of liver injury in the two groups was similar (52.2% versus 46.5% p=0.633). The difference in the post-transplantation cumulative survival rates between the groups with loss of anti-HBc (n=22) and no-loss (n=59) was significant (83.3% versus 43.1%, P =0.001).

CONCLUSION:

Loss of anti-HBc early in hematopoietic stem cell transplantation may help predict patient outcome.