Serum miRNAs predicting sustained HBs antigen reduction 48 weeks after pegylated interferon therapy in HBe antigen-negative patients

Koji Fujita, Shima Mimura, Hisakazu Iwama, Mai Nakahara, Kyoko Oura, Tomoko Tadokoro, Takako Nomura, Joji Tani, Hirohito Yoneyama, Asahiro Morishita, Makoto Oryu, Takashi Himoto, Hironori Nishitsuji, Kunitada Shimotohno, Masao Omata, Tsutomu Masaki

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Abstract

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.

Original languageEnglish
Article number1940
JournalInternational journal of molecular sciences
Volume19
Issue number7
DOIs
Publication statusPublished - 02-07-2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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  • Cite this

    Fujita, K., Mimura, S., Iwama, H., Nakahara, M., Oura, K., Tadokoro, T., Nomura, T., Tani, J., Yoneyama, H., Morishita, A., Oryu, M., Himoto, T., Nishitsuji, H., Shimotohno, K., Omata, M., & Masaki, T. (2018). Serum miRNAs predicting sustained HBs antigen reduction 48 weeks after pegylated interferon therapy in HBe antigen-negative patients. International journal of molecular sciences, 19(7), [1940]. https://doi.org/10.3390/ijms19071940