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

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.

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.

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.

FIB-6 demonstrated superior diagnostic performance compared to FIB-4 and APRI, showing greater accuracy in identifying advanced fibrosis and cirrhosis. Cutoff 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.