title: Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.
abstract: OBJECTIVE
  Interferon and nucleotide/nucleoside analogues are the main treatments for chronic hepatitis B. These drugs effectively reduce serum hepatitis B virus (HBV) DNA titers but fail to sufficiently reduce hepatitis B surface antigen (HBsAg) levels. Following the recent identification of sodium taurocholate cotransporting polypeptide as a receptor for HBV entry, inhibition of HBV entry has become an attractive therapeutic target for chronic hepatitis B treatment. We therefore evaluated the antiviral effects of antibody to HBsAg (anti-HBs) immunoglobulin (HBIG), which can inhibit HBV entry, by in an vivo study and a clinical trial.
  
  
  METHODS
  In the in vivo study, HBV-infected mice were generated from human hepatocyte chimeric mice and treated with HBIG. A clinical trial evaluating HBIG therapy in patients was also performed.
  
  
  RESULTS
  In the mouse study, HBV DNA titers were reduced and serum HBsAg titers decreased to undetectable levels following high-dose HBIG injection. On the basis of this result, eight chronic hepatitis B patients, who had received long-term nucleotide analogue treatment, were treated with monthly HBIG injections as an additional treatment. After 1 year of treatment, an HBsAg level reduction of more than 1 log IU/mL was observed in four patients, and three patients became anti-HBs positive. No adverse events occurred during HBIG therapy.
  
  
  CONCLUSIONS
  These results suggest that monthly HBIG injection might benefit patients with chronic hepatitis B whose HBsAg titer becomes lower following long-term nucleotide/nucleoside analogue treatment.
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Tsuge
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiraga
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kan
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Miyaki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Masaki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ono
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakahara
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe-Chayama
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Makokha Grace
authors.initials: MG
authors.lastname: Naswa
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kawaoka
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.|Laboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Miki
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aikata
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
authors.forename: C Nelson
authors.initials: CN
authors.lastname: Hayes
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. chayama@hiroshima-u.ac.jp.|Liver Research Project Center, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.|Laboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002678:Chimera; D003131:Combined Modality Therapy; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D017325:Hepatitis B Vaccines / Q000627:therapeutic use*; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000628:therapy* / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007136:Immunoglobulins; C045213:hepatitis B hyperimmune globulin
keywords: Anti-HBs immunoglobulin; Chronic hepatitis B; Hepatitis B surface antigen loss; Human hepatocyte chimeric mouse