Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection
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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.
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.
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.
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.
KeywordsChronic hepatitis B Human hepatocyte chimeric mouse Chronic hepatitis B Anti-HBs immunoglobulin Hepatitis B surface antigen loss
Antibody to hepatitis B surface antigen
Covalently closed circular DNA
Hepatitis B e antigen
Antibody to hepatitis B surface antigen immunoglobulin
Hepatitis B surface antigen
Hepatitis B virus
Sodium taurocholate cotransporting polypeptide
This study was supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Labor, Health and Welfare. The authors thank Rie Akiyama and Yoko Matsumoto for excellent technical assistance and Akemi Sada, Chikako Kanehara, and Emi Nishio for clerical assistance.
Compliance with ethical standards
Conflict of interest
Michio Imamura received honoraria from Bristol-Myers Squibb. Kazuaki Chayama received honoraria from Bristol-Myers Squibb and MSD. Masataka Tsuge and Michio Imamura received commercial research funding from Bristol-Myers Squibb. Kazuaki Chayama received commercial research funding from AbbVie, Dainippon Sumitomo Pharma, and RIKEN.