Combination of ursodeoxycholic acid and glycyrrhizic acid (Phosphogliv URSO) in the treatment of nonalcoholic fatty liver disease: results of a multicenter randomized clinical trial on efficacy and safety

The use of an original combination of ursodeoxycholic acid (UDCA) and glycyrrhizic acid (GA) as a component of pathogenetic therapy may enhance the effectiveness of treatment for nonalcoholic fatty liver disease (NAFLD) due to their complementary effects. Objective. To evaluate the efficacy, tolerability, and safety of a 12-week therapy for NAFLD with Phosphogliv URSO (capsules containing UDCA 250 mg and GA 35 mg) in comparison with UDCA monotherapy (Ursophalk, capsules 250 mg) and Phosphogliv (capsules containing phospholipids 65 mg and GA 35 mg). Material and methods. In a randomized, multicenter, comparative, open-label trial (n=225), the efficacy and safety of Phosphogliv URSO were assessed in patients with NAFLD over 12 weeks, compared with UDCA monotherapy and Phosphogliv. The primary endpoint was the change in aminotransferase level — alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Results. The hypothesis of superiority of the UDCA+GA combination with respect to the primary endpoint was confirmed in the Phosphogliv URSO group (n=75). More than a twofold reduction in ALT and AST levels was achieved (to 37.6±20.5 U/L and 31.5±16.7 U/L, respectively), exceeding the reductions in the UDCA group by 57% for ALT and 78% for AST (p<0.05). Improvements were also observed in the NAFLD Fibrosis Score (1.5-fold) and in other biochemical parameters (γ-glutamyl transferase, alkaline phosphatase, and lipid profile indices). No serious adverse events (AEs) were reported; mild transient AEs occurred at similar frequencies in the Phosphogliv URSO and UDCA groups (p>0.4), with the lowest incidence observed in the Phosphogliv group (p<0.05). Conclusion. GA, through its anti-inflammatory, antioxidant, and antifibrotic properties, enhances the therapeutic effect of UDCA. The synergistic action of GA in combination with UDCA or phospholipids on key pathogenetic mechanisms of NAFLD suggests that these regimens may represent a promising alternative to UDCA monotherapy.