Fixed-Dose Combinations of Glycyrrhizic Acid + Phospholipids and Glycyrrhizic Acid + Ursodeoxycholic Acid in the Treatment of Non-Alcoholic Fatty Liver Disease (Literature Review and Expert Council Resolution)

Abstract

Aim: to evaluate, based on an analysis of preclinical and clinical data, the efficacy and safety of fixed combinations of glycyrrhizic acid with phospholipids or ursodeoxycholic acid for the treatment of non-alcoholic fatty liver disease. Key points. Glycyrrhizic acid exerts antisteatotic, anti-inflammatory, and antifibrotic effects through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), the inhibition of sterol regulatory element-binding protein 1c (SREBP-1c), nuclear factor κB (NF-κB), and the modulation of the farnesoid X receptor (FXR)/sirtuin-1 (SIRT1) pathway. The “glycyrrhizic acid + phospholipids” fixed-dose combination (IV for 14 days followed by PO for 10 weeks) is recommended to reduce steatosis and inflammation and to prevent fibrosis (strength of recommendation: B; level of evidence: 2). In clinical studies, a 2–3-month therapy with the drug led to the normalization of aminotransferase activity in the majority of patients, while a 12-month study demonstrated regression of advanced stages of liver fibrosis (F2–F4), up to the complete disappearance of signs of cirrhosis (F4) in all patients. The “glycyrrhizic acid + ursodeoxycholic acid” fixed combination (12 weeks; 15 mg/kg/day of ursodeoxycholic acid) is recommended for patients with non-alcoholic fatty liver disease and elevated aminotransferase levels to reduce inflammation (strength of recommendation: B; level of evidence: 2). Randomized clinical trials have shown more than a twofold reduction in aminotransferase activity, as well as improvements in quality of life. An analysis of more than 1.3 million prescriptions confirms a favorable safety profile for both combinations (overall incidence of adverse events: 0.01–1.4 %, predominantly mild gastrointestinal disturbances). Conclusion. Fixed-dose combinations of “glycyrrhizic acid + phospholipids” and “glycyrrhizic acid + ursodeoxycholic acid” are effective and safe pharmacotherapeutic options for the treatment of non-alcoholic fatty liver disease, exhibiting antisteatotic, anti-inflammatory, and antifibrotic effect as supported by data from randomized clinical trials and post-marketing surveillance in the Russian Federation.