Persistent Loss of Hepatitis B Virus Markers in Serum without Cellular Immunity by Combination of Peginterferon and Entecavir Therapy in Humanized Mice.
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| Abstract |
Nucleot(s)ide analogues and peginterferon (PEG-IFN) treatment are the only approved therapies for chronic hepatitis B virus (HBV) infection. However, complete eradication of the virus, as indicated by persistent loss of hepatitis B surface antigen (HBsAg), is rare among treated patients. This is due to long-term persistence of the HBV genome in infected hepatocytes in the form of covalently closed circular DNA (cccDNA). In this study, we investigated whether administration of a large dose of a nucleoside analogue in combination with PEG-IFN can achieve long-term loss of HBsAg in human hepatocyte chimeric mice. Mice were treated with a high dose of entecavir and/or PEG-IFN for 6 weeks. High-dose combination therapy with both drugs resulted in persistently negative HBV DNA in serum. Although small amounts of HBV DNA and cccDNA (0.1 and 0.01 copy/cell, respectively) remained in the mouse livers, some of the mice remained persistently negative for serum HBV DNA at 13 weeks after cessation of the therapy. Serum HBsAg and hepatitis B core-related antigen (HBcrAg) continued to decrease and eventually became negative at 12 weeks after cessation of the therapy. Analysis of the HBV genome in treated mice showed accumulation of G-to-A hypermutation and CpG III island methylation. Persistent loss of serum HBV DNA and loss of HBV markers by high-dose entecavir and PEG-IFN combination treatment in chimeric mice suggests that control of HBV can be achieved even in the absence of a cellular immune response.
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| Authors | Takuro Uchida, Michio Imamura, C Nelson Hayes, Nobuhiko Hiraga, Hiromi Kan, Masataka Tsuge, Hiromi Abe-Chayama, Yizhou Zhang, Grace Naswa Makokha, Hiroshi Aikata, Daiki Miki, Hidenori Ochi, Yuji Ishida, Chise Tateno, Kazuaki Chayama |
| Journal | Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 61 Issue 9 (09 2017) ISSN: 1098-6596 [Electronic] United States |
| PMID | 28696237 (Publication Type: Journal Article) |
| Copyright | Copyright © 2017 American Society for Microbiology. |
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