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

Abstract 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.