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

Nat Commun. 2025 Jul 1;16(1):5969. doi: 10.1038/s41467-025-60755-9.

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.

Publication types

  • Randomized Controlled Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis / pathology
  • Liver Diseases, Alcoholic* / diet therapy
  • Liver Diseases, Alcoholic* / pathology
  • Liver Diseases, Alcoholic* / therapy
  • Male
  • Middle Aged
  • Nutritional Support* / methods
  • Treatment Outcome