The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial.
- 2025-07-01
- Nature communications 16(1)
- 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 Erhard Uschner
- Karolina Sulek
- Ida F Villesen
- Katrine P Lindvig
- Katrine H Thorhauge
- Nikolaj Torp
- Jane M Jensen
- Marisa Isabell Keller
- Gitte H Jensen
- Sönke Detlefsen
- Diana J Leeming
- Evelina Stankevic
- Tommi Suvitaival
- Andressa Zawadzki
- Michael Kuhn
- Lars Juhl Jensen
- Morten Karsdal
- Jonel Trebicka
- Hans Israelsen
- Cristina Legido-Quigley
- Peer Bork
- Manimozhiyan Arumugam
- Torben Hansen
- Maja Thiele
- Aleksander Krag
- PubMed: 40595534
- DOI: 10.1038/s41467-025-60755-9
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.
Research Insights
| Supplement | Health Outcome | Effect Type | Effect Size |
|---|---|---|---|
| Lactobacillus plantarum N13 | No Serious Treatment-Related Adverse Events | Beneficial | Small |
| Lactobacillus plantarum N13 | Reduced Liver Fibrosis | Beneficial | Small |