Abstract

Background:

Lubiprostone has been shown to improve intestinal permeability. We aimed to assess the safety and efficacy of lubiprostone in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods:

This randomised placebo-controlled trial was conducted in a specialized MASLD outpatient clinic at the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt, and recruited patients with radiological evidence of MASLD. Eligible patients were randomly assigned to either lubiprostone 24 μg or placebo orally twice daily for 48 weeks. The primary endpoint was a change from baseline in fat quantification by MRI-PDFF. Safety was assessed clinically and by laboratory testing. This trial was registered at Clincaltrials.gov (NCT05768334).

Results:

Between November 2020 and February 2023, we screened 176 patients of whom 116 were eligible. 57 patients received lubiprostone (group 1) while 59 patients received placebo (group 2). In groups 1 and 2, MRI-PDFF was technically unfeasible in 3 and 1 patient; 12 and 18 subjects were lost to followup, respectively, and 4 patients discontinued lubiprostone, leaving 40 in each group for final analysis. A greater reduction in fat quantity by MRI-PDFF from baseline to 48 weeks was seen in the lubiprostone group vs. placebo group (p=0.04; table 1) despite a statistically significant reduction in body weight in the control group compared to the lubiprostone group. However, no significant difference was found between both groups regarding liver stiffness measurement by Fibroscan or ALT levels. Severe diarrhea requiring treatment stoppage was encountered in one patient in the lubiprostone group. No other serious adverse events or mortality occurred.

Conclusion: Lubiprostone was well tolerated and reduced liver MRI-PDFF fat content in patients with MASLD over 48 weeks. Lubiprostone appears promising to treat MASLD, and warrants larger studies to confirm efficacy.