Lean metabolic dysfunction-associated steatotic liver disease: Current insights and knowledge gaps

Metabolic dysfunction-associated liver disease (MASLD) is on a rising trend globally. An approximate 10-20% of those with MASLD have a lean phenotype (lean MASLD) with prevalence higher in Asian population Thin-fat phenotype seen in Asians, increased visceral adipose tissue, insulin resistance and genetic polymorphisms are considered to contribute to this. Atherogenic dyslipidemia, diabetes mellitus, cardiovascular disease and sarcopenia may commonly co-exist in individuals with lean MASLD. Due to lack of clinical symptoms, it is often detected on routine screening. While the presence of comorbidities such as diabetes mellitus, hypertension and hypertriglyceridemia are more than lean healthy individuals, it remains lower than non-lean MASLD. However, advanced fibrosis and all cause mortality remain higher in the lean MASLD cohort highlighting they are a high-risk group. Diagnostic tests such as serum fibrosis indices as well as non-invasive imaging are commonly used, but data on its performance among lean MASLD is still emerging. Diet and lifestyle measures remain the cornerstone of treatment with agents like Vitamin E, Saroglitazar and Resmetirom showing beneficial results. Several promising agents are in the therapeutic pipeline. Additional studies investigating disease pathogenesis, performance of diagnostic tests and treatment targets in lean MASLD are needed to improve long-term management of affected individuals.