Lubiprostone Reduces Fat Content on MRI-PDFF in Patients With MASLD: A 48-Week Randomised Controlled Trial.

Background And Aims: The laxative lubiprostone has been shown to decrease intestinal permeability. We aimed to assess the safety and efficacy of lubiprostone administered for 48 weeks in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Approach And Results: A randomised placebo-controlled trial was conducted in a specialised MASLD outpatient clinic at the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt. The recruited patients had radiological evidence of MASLD along with other criteria for diagnosis. Eligible patients were randomly assigned to receive either placebo or lubiprostone 24 μg orally twice daily for 48 weeks. The liver fat content was quantified by magnetic resonance imaging estimated proton density fat fraction (MRI-PDFF). Between November 2020 and February 2023, 176 patients were screened, of whom 116 were eligible. Fifty-nine patients were randomised to receive placebo, while 57 patients were randomised to receive lubiprostone. Due mostly to patient dropout (i.e., loss to follow-up), complete data were available for 40 patients in each group. Compared with placebo group, 48-week lubiprostone treatment significantly reduced fat quantity (p = 0.04). Despite a significant reduction in body weight in the control group, no significant difference was found between both groups regarding fibrosis score by transient elastography or in serum ALT levels. One patient in the lubiprostone group developed severe diarrhoea requiring treatment stoppage. No other serious adverse events occurred.

Conclusion: Lubiprostone was well tolerated and reduced liver fat content as measured by MRI-PDFF in patients with MASLD over 48 weeks. Lubiprostone appears promising to treat MASLD and warrants more extensive studies to confirm such efficacy.

Trial Registration: ClinicalTrials.gov identifier: NCT05768334.