Natural history of metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), which has been the term for non-alcoholic fatty liver disease (NAFLD) since June 2023, represents the most common liver disease worldwide and is a leading cause of liver-related morbidity and mortality. A thorough knowledge of the disease's natural history is required to promptly stratify patients' risks, since MASLD is a multifaceted disorder with a broad range of clinical phenotypes. The histological disease spectrum ranges from isolated hepatic steatosis, currently named as metabolic dysfunction-associated steatotic liver (MASL), to metabolic dysfunction-associated steatohepatitis (MASH) and eventually may accumulate hepatic fibrosis and develop cirrhosis and/or hepatocellular carcinoma (HCC). Several risk factors for fibrosis progression have been identified, while the disease's progression displays notable dynamism and bidirectionality. When compared to the general population, all MASLD histological stages are substantially related with greater overall mortality, and this association exhibits a disease severity-dependent pattern. Interestingly, the fibrosis stage is the most accurate predictor of mortality among MASLD patients. The mortality attributed to MASLD predominantly stems from issues linked with the liver and cardiovascular system, as well as HCC and extrahepatic cancers. In light of the disease natural course, it is crucial to prioritize the identification of at-risk patients for disease progression in order to effectively address and change modifiable risk factors, hence mitigating disease complications. Further investigation is required to define the phenotype of rapid progressors more precisely as well as to improve risk stratification for HCC in non-cirrhotic individuals.