Is FIB-4 the right tool for screening for liver fibrosis?

Introduction and Objectives: The screening accuracy of non-invasive fibrosis tests like FIB-4 in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Using standard cut-offs, this study evaluated FIB-4 ' s agreement with vibration-controlled transient elastography (VCTE) and identified and validated new thresholds. Patients and Methods: A prospective cohort study (2019-2024) in Belgian and Dutch primary care used VCTE by FibroScan (R) (Echosens, France) as a proxy for the fibrosis stage. The FIB-4 index was derived from electronic patient data and study blood samples. Agreement between VCTE and FIB-4 was analysed using weighted Cohen's kappa. New fibrosis cut-offs (>= F2; >= 8 kPa) for <= 65 and >65 years were determined via Youden's Index and validated in a Turkish primary care cohort and a Belgian secondary care T2DM cohort. Results: Among 563 participants (median age 62 years, 47.1 % male, 14.2 % with T2DM, median BMI 28.2 kg/m & sup2;), FIB-4 showed poor agreement with VCTE (kappa = 0.138, 95 % CI: 0.069-0.207). Suggested new cut-offs of 1.29 (<= 65 years) and 1.72 (>65 years) were proposed. The 1.29 cut-off performed similarly to the existing 1.3 in validation cohorts. In the Turkiye and T2DM cohorts, the 1.72 cut-off improved sensitivity over 2.0 but had lower specificity. Conclusions: The FIB-4 index showed poor agreement with VCTE and low sensitivity, making it an unreliable standalone diagnostic tool for liver fibrosis in people with MASLD in both primary and secondary care. Alternative non-invasive tests or improved cut-off values are needed for accurate fibrosis detection in clinical practice.