Obesity and non-alcoholic fatty liver disease - how to treat comparatively growing epidemics

Abstract:

Despite the great interest in the issue of non-alcoholic fatty liver disease (NAFLD), the burden of the disease continues to grow, mainly as a result of the parallel progression of the obesity epidemic. Obesity has a negative impact on the function of almost all organs, including the liver. Excessive metabolic activity of visceral fat and dysregulation of adipokine synthesis, such as that found in individuals with central obesity, increase the level of proinflammatory mediators and promote the state of chronic systemic inflammation and endothelial dysfunction. Such an environment predisposes to the development of NAFLD, along with other components of the metabolic syndrome including dyslipidemia, arterial hypertension, and insulin resistance. A growing body of evidence suggests an important role of gut microbiota in the development of the disease. In patients with obesity and NAFLD, a 7–10% reduction in body weight results in a significant improvement of biochemical and histological parameters of steatosis and nonalcoholic steatohepatitis (NASH), and also in slowing down the progression of liver fibrosis. While many drugs are currently being investigated for the treatment of NAFLD, none has yet received formal approval from regulatory authorities. However, several classes of antihyperglycemic and anti-obesity drugs (pioglitazone, SGLT2 inhibitors, GLP-1RA, and multi-agonists) have shown favorable effects on liver enzymes levels, liver fat content and, in certain cases, on histologic features such as inflammation and fibrosis.

Key words:
obesity; insulin resistance; metabolic syndrome; non-alcoholic fatty liver disease