What is the FIB-4 Score?
The FIB-4 (Fibrosis-4) score is a simple, blood-based calculation using age, AST, ALT, and platelet count to non-invasively assess the probability of advanced liver fibrosis, serving as the most widely recommended first-line screening tool for identifying patients who need further hepatology evaluation. 1, 2
Calculation Formula
The FIB-4 score is calculated as: Age (years) × AST (IU/L) / [Platelet count (×10⁹/L) × √ALT (IU/L)] 1, 2
You need exactly four laboratory values to calculate it 2:
- Age in years
- AST (aspartate aminotransferase) in IU/L
- ALT (alanine aminotransferase) in IU/L
- Platelet count in ×10⁹/L
Clinical Interpretation and Thresholds
FIB-4 <1.3 (or <2.0 if age ≥65 years): Low probability of advanced fibrosis with approximately 90% negative predictive value, allowing you to confidently rule out advanced disease and repeat testing every 1-3 years in at-risk populations 1, 2, 3
FIB-4 1.3-2.67: Indeterminate range requiring second-tier testing with liver elastography (FibroScan/VCTE) or Enhanced Liver Fibrosis (ELF) testing, as approximately 30-40% of patients fall into this gray zone where the score cannot reliably confirm or exclude advanced fibrosis 1, 2, 3
FIB-4 >2.67: High probability of advanced fibrosis with approximately 65-80% positive predictive value, mandating immediate hepatology referral for comprehensive evaluation including consideration of elastography or liver biopsy 2, 3, 4
Diagnostic Performance
FIB-4 demonstrates an AUROC of approximately 0.77-0.86 for detecting advanced fibrosis, outperforming seven other simple non-invasive markers including NAFLD fibrosis score, APRI, BARD score, and AST/ALT ratio 3, 5, 4. The test excels at ruling out advanced fibrosis (high negative predictive value >90%) rather than confirming it 2, 5.
Critical Age-Related Limitation
Age significantly affects FIB-4 values because age is in the numerator of the formula, causing the score to naturally increase with advancing age. 2 This creates higher false-positive rates in elderly patients (requiring the adjusted cutoff of 2.0 instead of 1.3 for those ≥65 years) and potential false-negatives in younger patients under 35 years 1, 2.
Clinical Application in Practice
FIB-4 is recommended as the primary screening tool in patients with 1, 2:
- Type 2 diabetes
- Abdominal obesity plus ≥1 additional metabolic risk factor
- Persistently elevated liver enzymes
- Incidental finding of hepatic steatosis
The sequential testing strategy starts with FIB-4 as initial screening, followed by elastography or ELF score if FIB-4 falls in the indeterminate range 1, 2, 6. This approach is cost-effective and widely available, requiring only routine laboratory tests without specialized equipment 7, 8.
Performance Limitations to Recognize
FIB-4 has limited accuracy in the intermediate range (1.3-2.67), where it cannot reliably stratify risk without additional testing 1, 2. Diabetes and metabolic syndrome may reduce diagnostic accuracy in NAFLD populations 1. At a fixed specificity of 90% (FIB-4 = 1.93), sensitivity for identifying advanced fibrosis is only 50%, highlighting that while excellent for ruling out disease, it misses half of advanced fibrosis cases at this threshold 3.
Role in WHO and International Guidelines
Recent 2024-2025 guidelines from WHO, EASL-EASD-EASO, and systematic reviews in The Lancet Gastroenterology & Hepatology establish FIB-4 as a validated tool for staging liver fibrosis in chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease (MASLD), with specific cutoffs validated across multiple populations 1.