Long-Term Effects of Nalmefene on Alcohol Consumption, Liver Function, and Gut Microbiota in Patients With Alcohol-Related Liver Disease.

Abstract

Aim: Evidence concerning the long-term efficacy of nalmefene in alcohol-related liver disease (ALD) remains insufficient, particularly regarding gut microbiota alterations. This study evaluated the 12-month effects of nalmefene on alcohol consumption, liver function, and microbiota in the gut of patients with ALD.

Methods: This single-center retrospective study comprised 15 patients with ALD and alcohol consumption disorder who received nalmefene for 12 months. We investigated the changes in heavy drinking days, total alcohol consumption, and drinking risk level. Liver function parameters and adverse events were assessed longitudinally. Gut microbiota composition was analyzed at baseline and at 12 months.

Results: Both heavy drinking days and total alcohol consumption showed a significant reduction from month 4 and were maintained through month 12. Drinking risk level improved in 7 patients (46.7%) and showed no change in 8 (53.3%), with no worsening. Liver enzymes, including aspartate aminotransferase and γ-glutamyl transpeptidase, showed marked improvement, whereas hepatic functional reserve parameters remained stable. At the phylum level, a significant decrease in Proteobacteria, accompanied by a Klebsiella reduction at the genus level, was observed after treatment. No significant differences were observed in α-diversity indices. Adverse events were generally mild, occurred predominantly within the first month, and did not increase in severity over the long term.

Conclusions: Nalmefene was linked to sustained reductions in alcohol intake and improvements in liver enzyme levels over 12 months in patients with ALD. It may also play a role in beneficial modulation of the gut microbiota. Larger studies are required to validate these findings.