Original Article—Liver, Pancreas, and Biliary Tract

Journal of Gastroenterology

pp 1-8

First online:

Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection

  • Masataka TsugeAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityNatural Science Center for Basic Research and Development, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Nobuhiko HiragaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Takuro UchidaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Hiromi KanAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Eisuke MiyakiAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Keiichi MasakiAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Atsushi OnoAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Takashi NakaharaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
  • , Hiromi Abe-ChayamaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Yizhou ZhangAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Makokha Grace NaswaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Tomokazu KawaokaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Daiki MikiAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima UniversityLaboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN)
    • , Michio ImamuraAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Yoshiiku KawakamiAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Hiroshi AikataAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Hidenori OchiAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , C. Nelson HayesAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima University
    • , Kazuaki ChayamaAffiliated withDepartment of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Science, Hiroshima UniversityLiver Research Project Center, Hiroshima UniversityLaboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN) Email author 

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Abstract

Background and aims

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.

Conclusion

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.

Keywords

Chronic hepatitis B Human hepatocyte chimeric mouse Chronic hepatitis B Anti-HBs immunoglobulin Hepatitis B surface antigen loss