Combination of non-alcoholic fatty liver disease and cholelithiasis: Pathophysiological and clinical relationships and specific features of therapy. A review

Non-alcoholic fatty liver disease (NAFLD) and cholelithiasis (CL) are widespread diseases worldwide. The combination of NAFLD and CL is a common clinical situation. CL and NAFLD have common risk factors and are closely associated with such concomitant diseases as obesity, dyslipidemia, and carbohydrate metabolism disorders. Numerous studies in different populations have shown that NAFLD is an independent risk factor for CL, and CL is an independent risk factor for NAFLD. Insulin resistance is now being considered as a key link between NAFLD and the development of cholesterol cholelithiasis. In addition, changes in the expression of transcription factors, including hepatic X-receptor, farnesoid X-receptor, and membrane bile acid receptors, play an important role. It leads to increased lipogenesis in the liver and to bile cholesterol supersaturation, contributing to the development of gallstones and fatty liver. An equally important role in the pathogenesis of both diseases is played by gallbladder dysfunction, which serves as an important link between the liver and the intestine within the hepatic-gallbladder-intestinal axis and supports the metabolic homeostasis of cholesterol, triglycerides, and bile acids. It is supported by evidence that cholecystectomy increases the risk of NAFLD, contributes to insulin resistance, and promotes fat accumulation in the liver. The choice of drug therapy in patients with a combination of NAFLD and CL is based on knowledge of the general pathophysiological processes typical of both diseases. Drugs should comply with the principles of multipurpose monotherapy, targeting as many therapeutic targets as possible, and their combination should potentiate each other’s pharmacological effects. The treatment of patients with a combination of NAFLD and CL is primarily based on weight loss through exercise and a Mediterranean diet, enhanced by psyllium-containing agents and butyric acid, a key mediator of the Mediterranean diet’s positive effects. The drug of choice in patients with a combination of NAFLD and CL is ursodeoxycholic acid, exerting a pathogenetic effect on both diseases.