Journal of Gastroenterology

, Volume 51, Issue 11, pp 1073–1080

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

  • Masataka Tsuge
  • Nobuhiko Hiraga
  • Takuro Uchida
  • Hiromi Kan
  • Eisuke Miyaki
  • Keiichi Masaki
  • Atsushi Ono
  • Takashi Nakahara
  • Hiromi Abe-Chayama
  • Yizhou Zhang
  • Makokha Grace Naswa
  • Tomokazu Kawaoka
  • Daiki Miki
  • Michio Imamura
  • Yoshiiku Kawakami
  • Hiroshi Aikata
  • Hidenori Ochi
  • C. Nelson Hayes
  • Kazuaki Chayama
Original Article—Liver, Pancreas, and Biliary Tract

DOI: 10.1007/s00535-016-1189-x

Cite this article as:
Tsuge, M., Hiraga, N., Uchida, T. et al. J Gastroenterol (2016) 51: 1073. doi:10.1007/s00535-016-1189-x
  • 472 Downloads

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 BHuman hepatocyte chimeric mouseChronic hepatitis BAnti-HBs immunoglobulinHepatitis B surface antigen loss

Abbreviations

Anti-HBs

Antibody to hepatitis B surface antigen

cccDNA

Covalently closed circular DNA

HBeAg

Hepatitis B e antigen

HBIG

Antibody to hepatitis B surface antigen immunoglobulin

HBsAg

Hepatitis B surface antigen

HBV

Hepatitis B virus

NA

Nucleotide/nucleoside analogue

NTCP

Sodium taurocholate cotransporting polypeptide

Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  • Masataka Tsuge
    • 1
    • 2
    • 3
  • Nobuhiko Hiraga
    • 1
    • 3
  • Takuro Uchida
    • 1
    • 3
  • Hiromi Kan
    • 1
    • 3
  • Eisuke Miyaki
    • 1
    • 3
  • Keiichi Masaki
    • 1
    • 3
  • Atsushi Ono
    • 1
    • 3
  • Takashi Nakahara
    • 1
    • 3
  • Hiromi Abe-Chayama
    • 1
    • 3
  • Yizhou Zhang
    • 1
    • 3
  • Makokha Grace Naswa
    • 1
    • 3
  • Tomokazu Kawaoka
    • 1
    • 3
  • Daiki Miki
    • 1
    • 3
    • 4
  • Michio Imamura
    • 1
    • 3
  • Yoshiiku Kawakami
    • 1
    • 3
  • Hiroshi Aikata
    • 1
    • 3
  • Hidenori Ochi
    • 1
    • 3
  • C. Nelson Hayes
    • 1
    • 3
  • Kazuaki Chayama
    • 1
    • 3
    • 4
  1. 1.Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health ScienceHiroshima UniversityHiroshimaJapan
  2. 2.Natural Science Center for Basic Research and DevelopmentHiroshima UniversityHiroshimaJapan
  3. 3.Liver Research Project CenterHiroshima UniversityHiroshimaJapan
  4. 4.Laboratory for Liver Diseases, SNP Research CenterInstitute of Physical and Chemical Research (RIKEN)HiroshimaJapan