From non-alcoholic fatty liver disease to COVID­19: the present and prospects for the use of ursodeoxycholic acid

Abstract

The clinical morphological manifestations of the course of non‑alcoholic fatty liver disease in patients, non‑alcohol drinkers, include steatohepatosis, non‑alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. There are four basic mechanisms in the pathogenesis of non‑alcoholic fatty liver disease: bile acid lipotoxicity, insulin resistance, systemic inflammation, increased oxidative stress and lipid peroxidation. Non‑alcoholic fatty liver disease increases the risk of onset, development and progression of the cardiovascular diseases independently from other predictors and manifestations of the metabolic syndrome. The complex treatment of patients with coronary heart disease, combined with the non‑alcoholic fatty liver disease includes diet, physical exercises, body mass reduction and drug therapy. The medications for this category of patients must be maximal safe and result in the improving of the clinical, laboratory and morphological parameters of liver. Ursodeoxycholic acid is one of the most effective medications with the mechanisms of action associated with the normalization of the hepatoenteric circulation of bile acids and a number of biologically active substances. It also possesses the cytoprotective and antiapoptotic action, affects the FXR­metabolic nuclear receptor, which plays an important role in the physiology of vascular pathology, is an important transcriptional regulator of bile acids, lipids and glucose metabolism. Ursodeoxycholic acid is able to suppress eosinophilic inflammation not only in the gastrointestinal tract. It improves histopathological changes in airway remodeling, that can be connected with the modulation of cytokines and inhibition of apoptosis of epithelial cells of the respiratory tract. Ursodeoxycholic acid can be potentially effective preparation for the reduction of fluid volume in pulmonary edema and prevention of lung damage caused by fat embolism syndrome. Moreover, its positive effects have been proved as regards the airway epithelial cells at cystic fibrosis. Taking into account that ursodeoxycholic acid inhibits pro‑inflammatory cytokines, has strong antioxidative properties and acts as a famous hepatoprotector, it can be effective in the treatment of coronavirus disease (COVID­19). In Ukraine Ursonost is available, it is one of the well‑known preparations containing ursodeoxycholic acid and advantageously distinguished by high quality and ease of dosing. It is bioequivalent to the reference drug due to the highest quality of the substance and modern production technology. The large evidence base on ursodeoxycholic acid allows the drug Ursonost to be considered as a drug with pronounced multipotent properties, thus it is indicated for the treatment of patients with non‑alcoholic and alcoholic fatty liver disease, especially in combination with the coronary heart disease, of conditions, associated with bile reflux (duodenogastric, duodenogastroesophageal reflux), biliary sludge, primary biliary cirrhosis, gallstone disease (for dissolving X‑ray negative stones) and other metabolic disorders. Ursonost preparation is available as 150 and 300 mg capsules, that facilitates the drug dosing depending on the body mass of a patient and a clinical situation.