Masataka Tsuge1,2,3, Nobuhiko Hiraga1,3, Takuro Uchida1,3, Hiromi Kan1,3, Eisuke Miyaki1,3, Keiichi Masaki1,3, Atsushi Ono1,3, Takashi Nakahara1,3, Hiromi Abe-Chayama1,3, Yizhou Zhang1,3, Makokha Grace Naswa1,3, Tomokazu Kawaoka1,3, Daiki Miki1,3,4, Michio Imamura1,3, Yoshiiku Kawakami1,3, Hiroshi Aikata1,3, Hidenori Ochi1,3, C Nelson Hayes1,3, Kazuaki Chayama5,6,7. 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.
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-infectedmice 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.
Entities:
Keywords:
Anti-HBs immunoglobulin; Chronic hepatitis B; Hepatitis B surface antigen loss; Human hepatocyte chimeric mouse
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