MAFLD: a multisystem disease

Nonalcoholic fatty liver disease (NAFLD), affecting about 25% of general population and more than 50% of dysmetabolic patients, is an emerging cause of chronic liver disease and its complications. Recently, an international consensus of experts proposed to rename this disease as 'Metabolic dysfunction-Associated Fatty Liver Disease' (MAFLD) to focus on the bidirectional interplay between fatty liver and metabolic alterations and to stress the need of assessing fatty liver independently from alcohol consumption and other coexisting causes of liver disease. The peculiarity of NAFLD/MAFLD lies in the presence of a higher risk of not only - as expected - liver-related events but also of extrahepatic events, mostly cardiovascular and cancers. Available evidence suggests that these associations are not only the expression of sharing the same risk factors but shed light about the ability of NAFLD/MAFLD and particularly of its progressive form - nonalcoholic/metabolic dysfunction-associated steatohepatitis - to act as an independent risk factor via promotion of atherogenic dyslipidemia and a proinflammatory, profibrogenic, and procoagulant systemic environment. The present review summarizes available epidemiological and clinical evidence supporting the concept of NAFLD/MAFLD as a multisystemic disease, and highlights potential explanatory mechanisms underlying the association between NAFLD/MAFLD and extrahepatic disorders.

Automated summary

Nonalcoholic fatty liver disease (NAFLD), affecting a significant portion of both general and dysmetabolic populations, is an emerging cause of chronic liver disease and its complications. A recently proposed name for this disease, Metabolic dysfunction-Associated Fatty Liver Disease (MAFLD), highlights the bidirectional interplay between fatty liver and metabolic alterations, and emphasizes the need to assess fatty liver independently from other causes of liver disease. The peculiarity of NAFLD/MAFLD lies in its association with not only liver-related events, but also extrahepatic events, particularly cardiovascular and cancer-related. This review summarizes the available evidence supporting NAFLD/MAFLD as a multisystemic disease and explores the potential mechanisms underlying its association with extrahepatic disorders.