Metabolic dysfunction-associated steatotic liver disease (MASLD): definition, diagnosis, natural history, and treatment.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease, and strategies to prevent NAFLD-related hepatocellular carcinoma and liver failure are of increasing importance. Recently, the classification of steatotic liver disease (SLD) has been redefined based on alcohol intake: metabolic dysfunction-associated SLD (MASLD, mild alcohol intake), MASLD and increased alcohol intake (MetALD, moderate alcohol intake), and alcohol-related liver disease (ALD, heavy alcohol intake). Because the concordance rate between NAFLD and MASLD is 96-99%, MASLD can be regarded as clinically equivalent to NAFLD. When the risk of liver-related events is compared across these categories, ALD carries the highest risk, followed by MetALD and then MASLD. In contrast, the risk of cardiovascular events is highest in MASLD, followed by MetALD and ALD. All three subtypes also confer an increased risk of extrahepatic malignancies. Within MASLD, a distinct lean phenotype (lean MASLD) exists; compared with overweight MASLD, lean MASLD has a lower cardiovascular risk, but a higher risk of liver-related events. These findings highlight that complication risks differ among MASLD, MetALD, and ALD, necessitating phenotype-specific surveillance strategies. Although no pharmacotherapies for MASLD are currently approved in Japan, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors have been reported to improve histological inflammation and fibrosis in patients with MASLD, and their approval for MASLD is anticipated. Similarly, statins and pemafibrate have shown improvements in liver function and steatosis in patients with dyslipidaemia and are already used in routine clinical practice for comorbid cases.