Diagnostic Accuracy of FIB-4 Index and FIB-3 Index for Advanced Fibrosis in Chronic Liver Disease and Age-Specific Thresholds

Background and Aims: Given the high prevalence of chronic liver diseases, non-invasive assessment of liver fibrosis is critical for screening and management of these conditions. While the FIB-4 index is widely used, its age-dependent nature may reduce specificity in older adults. The FIB-3 index, which excludes age, has been proposed as an alternative. This study aimed to compare the diagnostic performance of FIB-3 and FIB-4 for detecting advanced fibrosis across age groups using magnetic resonance elastography (MRE) as the reference standard. Methods: We retrospectively analyzed 3424 patients aged ≥30 years with chronic liver disease who underwent MRE. Advanced fibrosis was defined as liver stiffness ≥ 3.62 kPa. The cutoff values and diagnostic performance of the FIB-4 and FIB-3 indices for advanced fibrosis were evaluated within subgroups stratified by age quartiles (Q1–Q4), and the areas under the ROC curves (AUROCs) were compared using DeLong’s test. Results: Both FIB-3 and FIB-4 indices demonstrated comparable diagnostic accuracy for advanced fibrosis (AUROC 0.82 (95% CI: 0.81–0.83) for both; p = 0.70). In age-stratified analysis, the cutoff values for the FIB-4 index increased with increasing age (Q1: 1.72, Q2: 2.90, Q3: 3.66, Q4: 4.20), reflecting its age-dependent formula. In contrast, the FIB-3 index exhibited relatively minor variation in cutoff values across quartiles (Q1: 2.32, Q2: 3.52, Q3: 3.74, Q4: 3.14). Conclusions: FIB-3 index offers similar diagnostic accuracy to FIB-4 index while demonstrating more consistent performance across age groups. These findings provide evidence that FIB-3 index may be a useful alternative, particularly in older populations where FIB-4 index interpretation may be confounded by age.