A prospective study of hepatitis B reactivation in patients with prior HBV exposure undergoing hematopoietic stem cell transplantation: reactivation association with graft-versus-host disease

Abstract

BACKGROUND AND AIMS: Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)-negative, antibody to the hepatitis B core antigen (anti-HBc)-positive individuals undergoing hematopoietic stem cell transplantation (HSCT) have not been well described. METHODS: From September 2011 onwards, we recruited treatmentnaive HBsAg-negative, anti-HBc-positive patients with baseline undetectable serum HBVDNA (<10 IU/mL), undergoing either autologous or allogenic HSCT. For allogenic HSCT, only recipients whose donors were HBsAg-negative were recruited. Liver biochemistry, serum HBVDNA, HBsAg and antibody to HBsAg (anti-HBs) were prospectively monitoring every 4 weeks after HSCT up to 2 years. Following guidelines from the European Association for the Study of the Liver, entecavir was started when HBV reactivation, defined as detectable HBVDNA (≥10 IU/mL) was encountered. RESULTS: At the time of writing, among 328 patients undergoing HSCT, 89 (27.3%) were HBsAg-negative, anti-HBc-positive, of whom 67 (75.3%) fulfilled our inclusion criteria and were recruited. The median duration of follow-up was 52 (range 4–104) weeks. The 2-year cumulative HBV reactivation rate, calculated using the Kaplan–Meier method, was 36.8%. Thirteen patients developed reactivation after a median duration of 44 (range 8–100) weeks, of whom 11 patients (84.6%) remained HBsAg-negative at reactivation. Median HBVDNA level at reactivation was 24.8 (range 14.6–428) IU/mL. Patients with acute and/or chronic graft-versus-host-disease (GVHD) had a significantly higher 2-year cumulative rate of HBV reactivation than those without (acute GVHD: 78.8% versus 22.4%, p = 0.006; chronic GVHD: 83.8% versus 23.3%, p < 0.001). Other clinical parameters, including age, anti-HBs status, and donor serology had no association with HBV reactivation (all p > 0.05). Multivariate Cox regression analysis showed that chronic GVHD was the only factor independently associated with reactivation (p = 0.030, hazard ratio 3.9, 95% confidence interval 1.1–13.8). Entecavir treatment successfully controlled HBV reactivation in all cases. CONCLUSIONS: From this interim analysis, a substantial proportion of HBsAg-negative, anti-HBc-positive patients developed HBV reactivation after HSCT, with risk of reactivation significantly higher in patients with chronic GVHD. Periodic HBVDNA monitoring was an effective strategy in preventing HBV-related complications.