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J Gastroenterol. 2016 Nov;51(11):1073-1080. Epub 2016 Mar 4.

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

Author information

1
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.
2
Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan.
3
Liver Research Project Center, Hiroshima University, Hiroshima, Japan.
4
Laboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan.
5
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.
6
Liver Research Project Center, Hiroshima University, Hiroshima, Japan. chayama@hiroshima-u.ac.jp.
7
Laboratory for Liver Diseases, SNP Research Center, Institute of Physical and Chemical Research (RIKEN), Hiroshima, Japan. chayama@hiroshima-u.ac.jp.

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:

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

PMID:
26943168
DOI:
10.1007/s00535-016-1189-x
[Indexed for MEDLINE]

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