The postbiotic ReFerm® versus standard nutritional support in advanced alcohol-related liver disease (GALA-POSTBIO): a randomized controlled phase 2 trial
Johanne K. Hansen, Mads Israelsen, Suguru Nishijima, Sara Stinson, Peter Andersen, Stine Johansen, Camilla Dalby Hansen, Maximilian Joseph Brol, Sabine Klein, Robert Schierwagen, Frank Erhard Uschner, Karolina Sulek, Ida Falk Villesen, Katrine Prier Lindvig, Katrine Holtz Thorhauge, Nikolaj Torp, Jane Møller Jensen, M. Keller, Gitte Hedegaard Jensen, Sönke Detlefsen, Diana Julie Leeming, Evelina Stankevič, Tommi Suvitaival, Andressa de Zawadzki, Michael Kuhn, Lars Juhl Jensen, M.A. Karsdal, Jonel Trebicka, Hans Israelsen, Cristina Legido‐Quigley, Peer Bork, Manimozhiyan Arumugam, Torben Hansen, Maja Thiele, Aleksander Krag
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. Impaired gut barrier function is a central driver of alcohol-related liver disease. This study indicates that the postbiotic ReFerm® improves gut barrier function and reduce liver stiffness and liver fibrosis, suggesting the gut barrier function as a potential treatment target.