Metabolic dysfunction-associated steatotic liver disease criteria may underestimate the number of lean female nonalcoholic fatty liver disease patients with significant liver fibrosis.

AIM: It remains unclear whether the newly defined concept of metabolic dysfunction-associated steatotic liver disease (MASLD) appropriately includes patients with nonalcoholic fatty liver disease with significant liver fibrosis. METHODS: A total of 4112 patients in whom nonalcoholic fatty liver disease was diagnosed by ultrasonography during medical checkups were enrolled. We defined a fibrosis-4 index ≥1.3 in patients aged <65 years and ≥2.0 in patients aged ≥65 years as significant liver fibrosis. RESULTS: The numbers of patients with a low, intermediate, and high probability of advanced fibrosis based on the fibrosis-4 index were 3360 (81.7%), 668 (16.2%), and 84 (2.0%). There were 3828 (93.1%) and 284 (6.9%) patients diagnosed with MASLD and non-MASLD. The non-MASLD group, compared with the MASLD group, was significantly younger (44 vs. 55 years) and had a higher percentage of women (62.3% vs. 27.7%). Significant fibrosis, defined based on the fibrosis-4 index, was present in 18.5% of the MASLD group and 15.5% of the non-MASLD group. In a multivariable analysis, female sex (OR 6.170, 95% CI 3.180-12.000; p < 0.001) was independently associated with non-MASLD in patients with a significant fibrosis. Among non-MASLD patients with a significant fibrosis (n = 44), body mass index was significantly lower in females than in males (p < 0.001). In a multivariable analysis of patients aged <65 years, female sex (OR, 7.700; 95% CI, 3.750-15.800; p < 0.001) remained independently associated with non-MASLD in patients with a significant fibrosis. CONCLUSIONS: MASLD may inappropriately exclude patients with significant fibrosis, especially lean females with nonalcoholic fatty liver disease.