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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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