Masamichi Kimura1, Koji Nishikawa1, Hisashi Sakamaki2, Masashi Mizokami3, Kiminori Kimura1. 1. Division of Hepatology. 2. Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan. 3. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Abstract
AIM: Patients with resolved hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although antiviral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated by immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB). Peripheral HBV-specific CD8+ T cells were analyzed for total numbers by flow cytometry and tetramer staining, as was intracellular γ-interferon (IFN-γ) production and CD107a expression in response to HBV peptides. Interleukin-10 (IL-10)-expressing CD19+ B-cell count and serum inflammatory cytokine levels were also analyzed. RESULTS: Serum HBV DNA was detectable in HSCT-treated patients with HBV reactivation at 12 months compared with other groups, indicating insufficient ETV efficacy against HBV. The HBV-specific CD8+ T-cell counts in HSCT-treated patients with HBV reactivation were significantly lower compared with those in non-HSCT patients. Additionally, IFN-γ production and CD107a expression by CD8+ T cells after incubation with HBV peptides was significantly reduced in HSCT-treated compared with CHB patients at 12 months after ETV treatment. Conversely, HSCT-treated patient serum IL-10 levels were significantly elevated compared with those in non-HSCT patients. Finally, IL-10-producing CD19+ B-cell counts were increased in HSCT-treated compared with CHB patients. CONCLUSION: After HBV reactivation, ETV efficacy was impaired in HSCT-treated patients as evidenced by low HBV-specific CD8+ T-cell counts and high B-cell IL-10 production.
AIM: Patients with resolved hepatitis B virus (HBV) infection following hematopoietic stem cell transplantation (HSCT) are potentially at high risk of HBV reactivation. Although antiviral drug therapy is recommended when HBV DNA reappears in the serum, drug efficacy after HBV reactivation remains unclear. METHODS: Host immune response against HBV was investigated by immunological analyses at 12 months after entecavir (ETV) treatment in six HSCT-treated and five non-HSCT-treated patients with HBV reactivation, and 18 patients with chronic hepatitis B (CHB). Peripheral HBV-specific CD8+ T cells were analyzed for total numbers by flow cytometry and tetramer staining, as was intracellular γ-interferon (IFN-γ) production and CD107a expression in response to HBV peptides. Interleukin-10 (IL-10)-expressing CD19+ B-cell count and serum inflammatory cytokine levels were also analyzed. RESULTS: Serum HBV DNA was detectable in HSCT-treated patients with HBV reactivation at 12 months compared with other groups, indicating insufficient ETV efficacy against HBV. The HBV-specific CD8+ T-cell counts in HSCT-treated patients with HBV reactivation were significantly lower compared with those in non-HSCT patients. Additionally, IFN-γ production and CD107a expression by CD8+ T cells after incubation with HBV peptides was significantly reduced in HSCT-treated compared with CHB patients at 12 months after ETV treatment. Conversely, HSCT-treated patient serum IL-10 levels were significantly elevated compared with those in non-HSCT patients. Finally, IL-10-producing CD19+ B-cell counts were increased in HSCT-treated compared with CHB patients. CONCLUSION: After HBV reactivation, ETV efficacy was impaired in HSCT-treated patients as evidenced by low HBV-specific CD8+ T-cell counts and high B-cell IL-10 production.