Improving MASLD Risk Stratification in Young Adults with Cardiometabolic Risk Factors and Insulin Resistance Assessment

Context: The fibrosis-4 index (FIB-4) index is recommended to identify adults with metabolic dysfunction-associated steatotic liver disease (MASLD) and clinically significant fibrosis (moderate to advanced fibrosis or ≥F2). However, it is less reliable in young adults (age <45 years). Objective: The aim was to assess whether cardiometabolic risk factors [CMRFs: type 2 diabetes (T2D), hypertension, obesity] or insulin resistance (IR) improved MASLD fibrosis risk stratification in young adults. Methods: Adults with/without T2D and no history of MASLD attending outpatient clinics underwent screening with vibration-controlled transient elastography for ≥F2 (liver stiffness measurement ≥ 8.0 kPa). Magnetic resonance elastography and/or liver biopsy were performed if indicated for diagnosis confirmation. Results: = .29), respectively. In young adults, clinically significant fibrosis was unlikely in those without homeostatic model assessment of insulin resistance (HOMA-IR) or CMRFs [negative predictive value (NPV) 97-100; 95% confidence interval 94-100]. Performance of FIB-4 ≥ 1.3 had low sensitivity (15%) and positive predictive value (25%) but good specificity (97%) and NPV (95%), whereas having 3 CMRFs alone performed better (sensitivity 75%, specificity 71%). Adding FIB-4 ≥ 1.3 to CMRFs worsened sensitivity (8%) while improving specificity (100%). Adding the HOMA-IR to CMRFs improved the sensitivity (75% to 78%) and specificity (75% to 81%) of CMRFs alone. Adding 2 CMRFs to the FIB-4 in the older age group improved both sensitivity and specificity of the FIB-4. Conclusion: In young adults, the absence of CMRFs or IR makes clinically significant fibrosis unlikely. Measuring IR improved risk stratification in young adults with CMRFs. Using CMRFs with IR may improve the detection of clinically significant fibrosis in young adults.