Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study
Abstract Aims Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-09-01
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| Series: | Health Science Reports |
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| Online Access: | https://doi.org/10.1002/hsr2.176 |
| _version_ | 1818574735615721472 |
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| author | Jun Arai Takayoshi Ito Yuu Shimozuma Manabu Uchikoshi Yoko Nakajima Masashi Sakaki Shojiro Uozumi Atsushi Kajiwara Ikuya Sugiura Yumi Otoyama Hisako Nozawa Toshikazu Kurihara Junichi Eguchi Norihiro Nomura Dai Sakuma Masashi Sato Yoshio Deguchi Hitoshi Yoshida |
| author_facet | Jun Arai Takayoshi Ito Yuu Shimozuma Manabu Uchikoshi Yoko Nakajima Masashi Sakaki Shojiro Uozumi Atsushi Kajiwara Ikuya Sugiura Yumi Otoyama Hisako Nozawa Toshikazu Kurihara Junichi Eguchi Norihiro Nomura Dai Sakuma Masashi Sato Yoshio Deguchi Hitoshi Yoshida |
| author_sort | Jun Arai |
| collection | DOAJ |
| description | Abstract Aims Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV‐infected patients during antiviral therapy and investigated the effects of viral eradication. Methods One hundred and eighty‐one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy. Results HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non‐major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN‐based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN‐free therapy was started and remained low during the therapy. Conclusions These results suggested that IFN‐free therapy potentially eradicated HCV in the B cells, leading to the down‐regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells. |
| first_indexed | 2024-12-15T00:30:30Z |
| format | Article |
| id | doaj.art-7c8f236966474a948503e4ce3cf88243 |
| institution | Directory Open Access Journal |
| issn | 2398-8835 |
| language | English |
| last_indexed | 2024-12-15T00:30:30Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Health Science Reports |
| spelling | doaj.art-7c8f236966474a948503e4ce3cf882432022-12-21T22:42:02ZengWileyHealth Science Reports2398-88352020-09-0133n/an/a10.1002/hsr2.176Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort studyJun Arai0Takayoshi Ito1Yuu Shimozuma2Manabu Uchikoshi3Yoko Nakajima4Masashi Sakaki5Shojiro Uozumi6Atsushi Kajiwara7Ikuya Sugiura8Yumi Otoyama9Hisako Nozawa10Toshikazu Kurihara11Junichi Eguchi12Norihiro Nomura13Dai Sakuma14Masashi Sato15Yoshio Deguchi16Hitoshi Yoshida17Department of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanInternal Medicine Showa University Karasuyama Hospital Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDigestive Disease Center Showa University Koto Toyosu Hospital Tokyo JapanDepartment of Medicine, Division of Gastroenterology Showa University School of Medicine Tokyo JapanAbstract Aims Hepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV‐infected patients during antiviral therapy and investigated the effects of viral eradication. Methods One hundred and eighty‐one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy. Results HCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non‐major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN‐based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN‐free therapy was started and remained low during the therapy. Conclusions These results suggested that IFN‐free therapy potentially eradicated HCV in the B cells, leading to the down‐regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.https://doi.org/10.1002/hsr2.176anti‐hepatitis C virus DAA (directly acting antivirals)B cellhepatitis C virusinterferonstissue tropism |
| spellingShingle | Jun Arai Takayoshi Ito Yuu Shimozuma Manabu Uchikoshi Yoko Nakajima Masashi Sakaki Shojiro Uozumi Atsushi Kajiwara Ikuya Sugiura Yumi Otoyama Hisako Nozawa Toshikazu Kurihara Junichi Eguchi Norihiro Nomura Dai Sakuma Masashi Sato Yoshio Deguchi Hitoshi Yoshida Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study Health Science Reports anti‐hepatitis C virus DAA (directly acting antivirals) B cell hepatitis C virus interferons tissue tropism |
| title | Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study |
| title_full | Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study |
| title_fullStr | Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study |
| title_full_unstemmed | Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study |
| title_short | Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study |
| title_sort | decreased expression of interferon stimulated genes in b cells of patients with chronic hepatitis c during interferon free therapy potentially suggests the eradication of hepatitis c virus in the b cells a cohort study |
| topic | anti‐hepatitis C virus DAA (directly acting antivirals) B cell hepatitis C virus interferons tissue tropism |
| url | https://doi.org/10.1002/hsr2.176 |
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