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The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial

Author

Listed:
  • Johanne K. Hansen

    (Odense University Hospital
    University of Southern Denmark)

  • Mads Israelsen

    (Odense University Hospital
    University of Southern Denmark)

  • Suguru Nishijima

    (European Molecular Biology Laboratory)

  • Sara E. Stinson

    (University of Copenhagen)

  • Peter Andersen

    (Odense University Hospital)

  • Stine Johansen

    (Odense University Hospital
    University of Southern Denmark)

  • Camilla D. Hansen

    (Odense University Hospital
    University of Southern Denmark)

  • Maximilian Joseph Brol

    (University of Münster)

  • Sabine Klein

    (University of Münster)

  • Robert Schierwagen

    (University of Münster)

  • Frank Erhard Uschner

    (University of Münster)

  • Karolina Sulek

    (Steno Diabetes Center Copenhagen)

  • Ida F. Villesen

    (Odense University Hospital
    University of Southern Denmark)

  • Katrine P. Lindvig

    (Odense University Hospital
    University of Southern Denmark)

  • Katrine H. Thorhauge

    (Odense University Hospital
    University of Southern Denmark)

  • Nikolaj Torp

    (Odense University Hospital
    University of Southern Denmark)

  • Jane M. Jensen

    (Odense University Hospital)

  • Marisa Isabell Keller

    (European Molecular Biology Laboratory)

  • Gitte H. Jensen

    (Odense University Hospital)

  • Sönke Detlefsen

    (University of Southern Denmark
    Odense University Hospital)

  • Diana J. Leeming

    (Nordic Bioscience A/S, Biomarkers & Research)

  • Evelina Stankevic

    (University of Copenhagen)

  • Tommi Suvitaival

    (Steno Diabetes Center Copenhagen)

  • Andressa Zawadzki

    (Steno Diabetes Center Copenhagen
    Nordic Bioscience A/S, Biomarkers & Research)

  • Michael Kuhn

    (European Molecular Biology Laboratory)

  • Lars Juhl Jensen

    (University of Copenhagen)

  • Morten Karsdal

    (Nordic Bioscience A/S, Biomarkers & Research)

  • Jonel Trebicka

    (Odense University Hospital
    University of Münster
    European Foundation for the Study of Chronic Liver Failure)

  • Hans Israelsen

    (Nordic Rebalance A/S)

  • Cristina Legido-Quigley

    (Steno Diabetes Center Copenhagen
    King’s College London)

  • Peer Bork

    (European Molecular Biology Laboratory
    Max Delbrück Centre for Molecular Medicine
    University of Würzburg)

  • Manimozhiyan Arumugam

    (Odense University Hospital
    University of Copenhagen)

  • Torben Hansen

    (University of Copenhagen)

  • Maja Thiele

    (Odense University Hospital
    University of Southern Denmark)

  • Aleksander Krag

    (Odense University Hospital
    University of Southern Denmark)

Abstract

Impaired gut barrier function may lead to progression of liver fibrosis in people with alcohol-related liver disease. The postbiotic ReFerm® can lower gut barrier permeability and may thereby reduce fibrosis formation. Here, we report the results from an open-labelled, single centre randomized controlled trial where 56 patients with advanced, compensated, alcohol-related liver disease were assigned 1:1 to receive either ReFerm® (n = 28) or standard nutritional support (Fresubin®, n = 28) for 24 weeks. The primary outcome was a ≥ 10% reduction of the fibrosis formation marker alpha-smooth muscle actin in liver biopsies, assessed by a blinded pathologist using automated digital imaging analysis. Paired liver biopsies meeting quality criteria for the primary outcome were available for 40 participants (ReFerm®, n = 21 and Fresubin®, n = 19). This reduction was observed in 29% of patients receiving ReFerm®, compared to 14% with Fresubin® (OR = 2.40; 95% CI 0.63 to 9.16; p = 0.200). No treatment-related serious adverse events occurred. Our findings suggest that ReFerm® may reduce liver fibrosis by enhancing gut barrier function, potentially preventing the progression of alcohol-related liver disease.

Suggested Citation

  • Johanne K. Hansen & Mads Israelsen & Suguru Nishijima & Sara E. Stinson & Peter Andersen & Stine Johansen & Camilla D. Hansen & Maximilian Joseph Brol & Sabine Klein & Robert Schierwagen & Frank Erhar, 2025. "The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60755-9
    DOI: 10.1038/s41467-025-60755-9
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    References listed on IDEAS

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