Hepatitis B reactivation in HBsAg-negative/HBcAb-positive allogeneic haematopoietic stem cell transplant recipients: risk factors and outcome

Clin Microbiol Infect. 2014 Oct;20(10):O694-701. doi: 10.1111/1469-0691.12611. Epub 2014 Mar 29.

Abstract

HBsAg-negative/HBcAb-positive haematopoietic stem cell transplant (HSCT) recipients are at high risk of hepatitis B virus (HBV) reactivation. Allogeneic HSCT recipients from years 2000 to 2010 were evaluated in order to study the impact of being HBsAg-negative/HBcAb-positive in this population. Overall, 137 of 764 patients (18%) were HBsAg-negative/HBcAb-positive before HSCT. Overall survival, non-relapse mortality (NRM), acute and chronic graft-vs.-host disease were similar in HBcAb-positive and HBcAb-negative patients. Reactivation occurred in 14 patients (10%) within a median of 19 months after HSCT (range 9-77). Cause-specific hazard for reactivation was decreased in the case of an HBV-immune/exposed donor (HRadjusted = 0.12; 95% CI, 0.02-0.96; p 0.045) and increased in patients who received rituximab treatment (HRadjusted = 2.91; 95%CI, 0.77-10.97; p 0.11). Competing risk analyses documented a protective role of an HBV-immune/exposed donor (p 0.041) and an increased probability associated with the length of treatment with cyclosporine (p <0.001) and treatment with rituximab (but not with low-dose rituximab prophylaxis, p <0.001 at each landmark point). No differences in overall survival and NRM were found between patients with and without HBV reactivation. The donor's immunity was independently and consistently associated with a decreased risk of HBV reactivation, while rituximab and cyclosporine treatments increased the probability.

Keywords: Bone marrow transplant; chronic graft-vs.-host disease; cyclosporin; occult HBV; resolved HBV hepatitis; reverse seroconversion; rituximab.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Child
  • Cyclosporine / adverse effects
  • Female
  • Graft vs Host Disease / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hepatitis B Surface Antigens / analysis*
  • Hepatitis B virus / physiology*
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Male
  • Middle Aged
  • Risk Factors
  • Rituximab
  • Survival Analysis
  • Transplant Recipients
  • Transplantation, Homologous
  • Treatment Outcome
  • Virus Activation*
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Hepatitis B Surface Antigens
  • Immunosuppressive Agents
  • Rituximab
  • Cyclosporine