The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial
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 random...
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2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60755-9 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Johanne K. Hansen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6f3a0d8a37b948aea8361bda69da6460 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-6f3a0d8a37b948aea8361bda69da64602025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116111610.1038/s41467-025-60755-9The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trialJohanne K. Hansen0Mads Israelsen1Suguru Nishijima2Sara E. Stinson3Peter Andersen4Stine Johansen5Camilla D. Hansen6Maximilian Joseph Brol7Sabine Klein8Robert Schierwagen9Frank Erhard Uschner10Karolina Sulek11Ida F. Villesen12Katrine P. Lindvig13Katrine H. Thorhauge14Nikolaj Torp15Jane M. Jensen16Marisa Isabell Keller17Gitte H. Jensen18Sönke Detlefsen19Diana J. Leeming20Evelina Stankevic21Tommi Suvitaival22Andressa Zawadzki23Michael Kuhn24Lars Juhl Jensen25Morten Karsdal26Jonel Trebicka27Hans Israelsen28Cristina Legido-Quigley29Peer Bork30Manimozhiyan Arumugam31Torben Hansen32Maja Thiele33Aleksander Krag34Department of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalMolecular Systems Biology Unit, European Molecular Biology LaboratoryNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Internal Medicine B, University of MünsterDepartment of Internal Medicine B, University of MünsterDepartment of Internal Medicine B, University of MünsterDepartment of Internal Medicine B, University of MünsterSteno Diabetes Center CopenhagenDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalMolecular Systems Biology Unit, European Molecular Biology LaboratoryDepartment of Pathology, Odense University HospitalDepartment of Clinical Research, Faculty of Health Sciences, University of Southern DenmarkNordic Bioscience A/S, Biomarkers & ResearchNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenSteno Diabetes Center CopenhagenSteno Diabetes Center CopenhagenMolecular Systems Biology Unit, European Molecular Biology LaboratoryNovo Nordisk Foundation Center for Protein Research, CPR, University of CopenhagenNordic Bioscience A/S, Biomarkers & ResearchDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalNordic Rebalance A/SSteno Diabetes Center CopenhagenMolecular Systems Biology Unit, European Molecular Biology LaboratoryDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalDepartment of Gastroenterology and Hepatology, Centre for Liver Research, Odense University HospitalAbstract 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.https://doi.org/10.1038/s41467-025-60755-9 |
| spellingShingle | 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 The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial Nature Communications |
| title | The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial |
| title_full | The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial |
| title_fullStr | The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial |
| title_full_unstemmed | The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial |
| title_short | The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial |
| title_sort | postbiotic referm r versus standard nutritional support in advanced alcohol related liver disease gala postbio a randomized controlled phase 2 trial |
| url | https://doi.org/10.1038/s41467-025-60755-9 |
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