Nonalcoholic fatty liver disease associated with obesity and type 2 diabetes and gut dysbiosis

Abstract

The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) parallels the global epidemic of obesity and type 2 diabetes mellitus (T2DM) worldwide. NAFLD increases the risk of T2DM, cardiovascular di­sease, and chronic kidney disease. Conversely, obesity and T2DM increase morbidity and mortality from NAFLD. Synchronous metabolic dysfunction in obesity and T2DM and gut dysbiosis exacerbate hepatic and systemic inflammation due to direct activation of innate and adaptive immune responses. Gut dysbiosis can contribute to the emergence and development of NAFLD, as well as acceleration of its progression to liver cirrhosis and hepatocellular carcinoma. Currently, lifestyle changes based on diet and exercise are the first step in the treatment of patients with NAFLD. Specific dietary interventions contribute to the improvement of NAFLD by modulating the gut-liver axis. Physical activity increases the sensitivity of insulin receptors, and in combination with diet leads to a reliably significant improvement in biochemical and histological indicators in patients with NAFLD combined with obesity and T2DM. Physical activity also modulates gut microbiota composition. Specific pharmacological treatment is performed mainly in patients with nonalcoholic steatohepatitis and biopsy-proven fibrosis, as well as a high risk of progression (older age, T2DM, metabolic syndrome, persistent elevation of alanine aminotransfe­rase). However, there are few available treatment options for NAFLD. Since gut microbiota is actively involved in the pathogenesis of NAFLD, exposure to it with probiotics, prebiotics or synbiotics in order to improve the liver phenotype is reasonable. At the congress of the European Association for the Study of the Liver, which took place in Vienna on June 21–24, 2023, a new classification and nomenclature of NAFLD was adopted. It was proposed to replace the term “nonalcoholic fatty liver disease” with the term “metabolic dysfunction-associated steatotic liver disease”. This diagnosis is established in patients with confirmed steatosis of the liver and one of five cardiometabolic risk factors: obesity, T2DM, insulin resistance, hyperlipidemia, atherosclerosis. The concept of “nonalcoholic steatohepatitis” has been changed to the concept of “metabolic dysfunction-associated steatohepatitis”. Coordination of the views of international and domestic experts in the field of studying this pathology will be important for clinical practice and scientific research.