Diabetes and obesity reduce FIB-4 accuracy in MASLD referral pathways.

Background & Aims: Primary care referral pathways often use FIB-4 to triage metabolic dysfunction-associated steatotic liver disease (MASLD), but its accuracy may vary by patient characteristics. We aimed to evaluate FIB-4 performance against elastography, compare it with other non-invasive tests, assess effect modification by BMI, diabetes, sex, ALT, and age, and calibrate 2D shear-wave elastography (2D-SWE) and vibration-controlled transient elastography (VCTE) thresholds. Methods: We analyzed two cohorts with paired serum scores and elastography: Calgary (2D-SWE; N = 8,126) and Edmonton (VCTE; N = 985). We summarized fibrosis-risk distributions and used exceedance probabilities to align 2D-SWE with guideline-recommended VCTE cut-offs. Results: In the Calgary cohort, median 2D-SWE was 4.6 kPa (IQR 3.9-5.8) and 9% had liver stiffness ≥8 kPa; FIB-4 was <1.30 in 70% and ≥2.67 in 5%. In the Edmonton cohort, median VCTE was 5.3 kPa (4.4-6.6) and 14% had liver stiffness ≥8 kPa; FIB-4 was <1.30 in 77% and ≥2.67 in 3%. In exceedance models, at a FIB-4 of 1.30, the probability of liver stiffness ≥8 kPa was significantly higher in individuals with diabetes or BMI ≥30 kg/m Conclusion: FIB-4 alone under-triages patients with diabetes and/or obesity. These patients should be fast-tracked to elastography even when FIB-4 is <1.30. We recommend validating these findings in other cohorts, as they may affect triaging practices. Impact and implications: Recent guidelines recommend clinical care pathways for risk stratification of patients with MASLD (metabolic dysfunction-associated steatotic liver disease) using sensitive serum-based markers (