Beyond Biopsy: Real-World Evaluation of the FIB-6 Score in a Portuguese Cohort

Introduction: Liver fibrosis is a key determinant of morbidity and mortality in chronic liver disease. Noninvasive scores such as Fibrosis-4 index (FIB-4) and AST to Platelet Ratio Index (APRI) are widely used, but their accuracy varies across populations. Fibrosis-6 score (FIB-6), a novel composite biomarker incorporating age, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, platelet count, and albumin improves fibrosis prediction. This study evaluated the diagnostic performance of FIB-6 in a Portuguese cohort with steatotic liver disease. Methods: This observational study analyzed 301 adult patients who underwent transient elastography. Demographic, clinical, and laboratory data were retrospectively collected. Noninvasive scores (FIB-4, APRI, and FIB-6) were calculated, and liver fibrosis (F0–F4) was assessed based on liver stiffness measure adjusted for liver disease etiology. Receiver operating characteristic (ROC) analyses, correlations with liver stiffness, Youden index–derived cutoffs, and rule-in/rule-out thresholds were subsequently performed. A subanalysis was also conducted for liver disease etiologies. Results: FIB-6 correlated moderately with liver stiffness (r=0.334; p<0.001), significantly outperforming FIB-4 and APRI, which showed weak or nonsignificant correlations. Area under the ROC Curve values for cirrhosis (F4) were 0.716 (FIB-6), 0.579 (APRI), and 0.513 (FIB-4); for advanced fibrosis (F3–F4), 0.709 (FIB-6), 0.568 (APRI), and 0.545 (FIB-4). Optimal Youden cutoffs for FIB-6 were >2.06 for advanced fibrosis and >1.69 for cirrhosis. A rule-in threshold of >2.30 achieved 90% specificity, while a rule-out threshold of <1.5 reached 90% sensitivity, for advanced fibrosis. FIB-6 outperformed FIB-4 and APRI across Metabolic Dysfunction–Associated Steatotic Liver Disease, Metabolic and Alcohol-Related Steatotic Liver Disease and Alcohol-Related Liver Disease. Discussion: FIB-6 demonstrated superior diagnostic performance compared to FIB-4 and APRI, showing greater accuracy in identifying advanced fibrosis and cirrhosis. Cut-off values varied across different etiologies, underscoring the importance of etiology-specific thresholds for optimal clinical application. Despite its robustness, laboratory-based scores may be influenced by physiological or clinical variations, requiring contextual interpretation. FIB-6 is a reliable and accessible noninvasive tool. Its application within a tripartite “rule-in/rule-out” framework can effectively guide clinical triage and prioritize patients for elastography, particularly in resource-limited settings.