Excess Body Weight and Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD)

Background: Nonalcoholic fatty liver disease (NAFLD) describes a continuum of liver abnormalities from simple nonalcoholic fatty liver (NAFL) to nonalcoholic fatty liver hepatitis or steatohepatitis (NASH) to NASH fibrosis. It has a variable course, but just like alcoholic fatty liver disease, it can lead to liver cirrhosis and cancer (hepatocellular carcinoma). Summary: NAFLD is a clinical entity characterized by the presence of liver steatosis, which affects at least 5% of hepatocytes. Affected are people who consume little or no alcohol and who have no secondary cause of liver steatosis such as viral hepatitis, drug intake (e.g., tamoxifen, amiodarone, methotrexate, etc.), or lipodystrophy. NAFLD is, nowadays, the most common liver disease in Europe, with an estimated prevalence of 25%. The currently widely recognized recommendation for the therapy of NAFLD is a lifestyle modification with the goal of weight loss. Although no drugs are currently approved for the treatment of NAFLD, several candidates are in clinical trials. Besides weight loss and physical activity, corresponding single active ingredients or combination therapies are intended to stop the progression of the disease and, in the best case, reverse it. The newly propagated name MAFLD (metabolic-associated fatty liver disease) should indicate that the disease is associated with metabolic disorders. The term MAFLD also implies multiple overlapping causes and drivers of this soaring disease. Key Messages: The prevalence of NAFLD continues to rise worldwide. NAFLD, NASH, and fibrosis in NAFLD occur predominantly in patients with obesity and type 2 diabetes (T2DM) or else precede these conditions. The progression of NAFLD is highly dependent on changes in glucose, lipid metabolism, and fibrogenesis. A new definition and nomenclature of fatty liver disease, “metabolic associated fatty liver disease” (MAFLD), should be discussed carefully, since around 40% of the global population with NAFLD are classified as non-obese and almost 1/5 as lean. Since the pathogenesis of fatty liver disease, obesity, and glucose and lipid metabolism diseases are very closely related, it is important to continue to look for mechanisms that these diseases have in common and develop new therapeutic approaches.