Lean Metabolic Dysfunction-Associated Steatotic Liver Disease: A Wolf in Sheep's Clothing

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 32.4% of the global population. It is expected to be the primary cause of end-stage liver disease and liver transplantation. Obesity is a major risk factor for MASLD. However, a subset of patients with MASLD does not exhibit obesity-related traits, and this group is frequently neglected in clinical workups. Therefore, these patients do not receive timely diagnosis and treatment. Research has shown that MASLD is a multisystemic disease that is linked not only to type 2 diabetes mellitus but also to end-stage liver disorders (cirrhosis, liver failure, and hepatocellular carcinoma), cardiovascular disease, and chronic kidney disease. Thus, lean patients with MASLD are likely to develop liver fibrosis and end-stage liver disease. They are also at a high risk of cardiovascular disease and mortality. In this review, we systematically summarized the epidemiological characteristics and pathophysiological mechanisms of lean MASLD to elucidate the clinical profile and molecular basis of this disease subtype while proposing targeted integrated management strategies. By addressing critical gaps in current clinical practice, including shortcomings in screening, incomplete risk assessment frameworks, and the lack of individualized treatment approaches, this review provides practical guidance for reducing the risk of end-stage liver disease and extrahepatic complications in this patient population.