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Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients
The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecu...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073286/ https://www.ncbi.nlm.nih.gov/pubmed/30004437 http://dx.doi.org/10.3390/ijms19071940 |
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author | Fujita, Koji Mimura, Shima Iwama, Hisakazu Nakahara, Mai Oura, Kyoko Tadokoro, Tomoko Nomura, Takako Tani, Joji Yoneyama, Hirohito Morishita, Asahiro Oryu, Makoto Himoto, Takashi Nishitsuji, Hironori Shimotohno, Kunitada Omata, Masao Masaki, Tsutomu |
author_facet | Fujita, Koji Mimura, Shima Iwama, Hisakazu Nakahara, Mai Oura, Kyoko Tadokoro, Tomoko Nomura, Takako Tani, Joji Yoneyama, Hirohito Morishita, Asahiro Oryu, Makoto Himoto, Takashi Nishitsuji, Hironori Shimotohno, Kunitada Omata, Masao Masaki, Tsutomu |
author_sort | Fujita, Koji |
collection | PubMed |
description | The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecutive chronic HBV infection patients negative for HBe antigen (HBeAg) with HBV-DNA levels <5 log copies/mL, alanine aminotransferase (ALT) <100 U/L, and compensated liver functions, were enrolled. The patients were subcutaneously injected with Peg-IFNα-2a weekly for 48 weeks (treatment period), followed by the 48-week observation period. HBsAg 1-log drop relative to baseline levels recorded at the end of the observation period was considered effective. Sera were obtained at weeks 0 and 24 during the treatment period analyzed for microRNAs. The microRNA (miRNA) antiviral activity was evaluated in vitro using Huh7/sodium taurocholate cotransporting polypeptide (NTCP) cells. As a result, six patients achieved the HBsAg 1-log drop after the observation periods. Comparison of serum microRNA levels demonstrated that high miR-6126 levels at week 24 predicted HBsAg 1-log drop. Furthermore, miR-6126 reduced HBsAg in culture medium supernatants and intracellular HBV-DNA quantities in Huh7/NTCP cells. In conclusion, high serum miR-6126 levels during Peg-IFN therapy predicted the HBsAg 1-log drop 48 weeks after the completion of therapy. In vitro assays revealed that miR-6126 was able to suppress HBsAg production and HBV replication. |
format | Online Article Text |
id | pubmed-6073286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60732862018-08-13 Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients Fujita, Koji Mimura, Shima Iwama, Hisakazu Nakahara, Mai Oura, Kyoko Tadokoro, Tomoko Nomura, Takako Tani, Joji Yoneyama, Hirohito Morishita, Asahiro Oryu, Makoto Himoto, Takashi Nishitsuji, Hironori Shimotohno, Kunitada Omata, Masao Masaki, Tsutomu Int J Mol Sci Article The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecutive chronic HBV infection patients negative for HBe antigen (HBeAg) with HBV-DNA levels <5 log copies/mL, alanine aminotransferase (ALT) <100 U/L, and compensated liver functions, were enrolled. The patients were subcutaneously injected with Peg-IFNα-2a weekly for 48 weeks (treatment period), followed by the 48-week observation period. HBsAg 1-log drop relative to baseline levels recorded at the end of the observation period was considered effective. Sera were obtained at weeks 0 and 24 during the treatment period analyzed for microRNAs. The microRNA (miRNA) antiviral activity was evaluated in vitro using Huh7/sodium taurocholate cotransporting polypeptide (NTCP) cells. As a result, six patients achieved the HBsAg 1-log drop after the observation periods. Comparison of serum microRNA levels demonstrated that high miR-6126 levels at week 24 predicted HBsAg 1-log drop. Furthermore, miR-6126 reduced HBsAg in culture medium supernatants and intracellular HBV-DNA quantities in Huh7/NTCP cells. In conclusion, high serum miR-6126 levels during Peg-IFN therapy predicted the HBsAg 1-log drop 48 weeks after the completion of therapy. In vitro assays revealed that miR-6126 was able to suppress HBsAg production and HBV replication. MDPI 2018-07-02 /pmc/articles/PMC6073286/ /pubmed/30004437 http://dx.doi.org/10.3390/ijms19071940 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Fujita, Koji Mimura, Shima Iwama, Hisakazu Nakahara, Mai Oura, Kyoko Tadokoro, Tomoko Nomura, Takako Tani, Joji Yoneyama, Hirohito Morishita, Asahiro Oryu, Makoto Himoto, Takashi Nishitsuji, Hironori Shimotohno, Kunitada Omata, Masao Masaki, Tsutomu Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title | Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title_full | Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title_fullStr | Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title_full_unstemmed | Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title_short | Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients |
title_sort | serum mirnas predicting sustained hbs antigen reduction 48 weeks after pegylated interferon therapy in hbe antigen-negative patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073286/ https://www.ncbi.nlm.nih.gov/pubmed/30004437 http://dx.doi.org/10.3390/ijms19071940 |
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