Immunomodulatory and Anti-Inflammatory Effects of Ketotifen Versus Vitamin E in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Pilot Study

Background: Non-alcoholic fatty liver disease (NAFLD) represents a prevalent, long-standing hepatic condition marked by the accumulation of fat in the liver and varying degrees of fibrotic changes. Ketotifen, a mast cell stabilizer, has been proposed to modulate inflammation and fibrogenesis, but clinical evidence is limited. Objective: To assess the effectiveness and safety of ketotifen vs vitamin E in individuals with NAFLD. The primary outcome was the change in hepatic steatosis, while the secondary outcomes included modifications in fibrosis-related indices and inflammatory biomarkers. In addition to other biochemical, anthropometric, and metabolic parameters. Methods: In this randomized study, 60 individuals with NAFLD were allocated in a 1:1 ratio into two groups. The vitamin E group was treated with vitamin E, and the ketotifen group received ketotifen for six months. Anthropometric parameters, liver steatosis and fibrosis, lipid profile, glycemic markers, liver enzymes, matrix metalloproteinase (MMP)-9, and tumor necrosis factor (TNF)-α were measured before and after 6 months. Results: Ketotifen treatment resulted in significant improvements in hepatic steatosis and disease activity compared with vitamin E, including lower steatosis and FibroScan-AST (FAST) score. Fibrosis severity was also reduced, with significant decreases in fibrosis score and fibrosis index (FIB-4) index, whereas Metabolic-Associated Steatosis Combined with Keratin-18 (MACK-3) score showed no significant between-group change. Glycemic outcomes improved significantly with ketotifen, including reductions in HOMA-IR, fasting blood glucose, and fasting insulin. Ketotifen also significantly reduced AST, TNF-α and MMP-9, and improved central adiposity measures (hip circumference, waist-stature ratio. No significant differences were observed for lipid profile, body weight, body mass index, or HbA1c. Ketotifen was generally well tolerated; drowsiness was the most common adverse event. Conclusion: Ketotifen exerts superior hepatoprotective, anti-inflammatory, antifibrotic, and insulin-sensitizing effects compared with vitamin E in NAFLD. These findings suggest that ketotifen may offer a promising adjunctive therapy for NAFLD. Clinical Trial Registration: NCT05616442.