How to Calculate FIB-4 Index
The Formula
The FIB-4 index is calculated using the following formula: Age (years) × AST (IU/L) / [Platelet count (×10⁹/L) × √ALT (IU/L)] 1, 2.
This formula was originally developed in patients co-infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but has since been validated across multiple chronic liver disease populations 1, 3.
Required Laboratory Values
To compute FIB-4, you need exactly four values 2:
- Age in years
- AST (aspartate aminotransferase) in IU/L
- ALT (alanine aminotransferase) in IU/L
- Platelet count in ×10⁹/L (or multiply by 10⁹ if given in cells/μL)
Step-by-Step Calculation
- Multiply the patient's age by their AST level 1, 2
- Calculate the square root of the ALT value 1, 2
- Multiply the platelet count by the square root of ALT 1, 2
- Divide the result from step 1 by the result from step 3 1, 2
Interpretation of Results
The Korean Association for the Study of the Liver provides clear cutoff values for clinical decision-making 1:
- FIB-4 <1.3: Low probability of advanced fibrosis with approximately 90% negative predictive value; advanced fibrosis can be ruled out 2, 4
- FIB-4 1.3-2.67: Indeterminate range requiring additional testing such as vibration-controlled transient elastography (VCTE) or Enhanced Liver Fibrosis (ELF) testing 1, 2
- FIB-4 >2.67: High probability of advanced fibrosis with 60-82% positive predictive value and 97-98% specificity 2, 4
Clinical Performance Characteristics
The FIB-4 index demonstrates strong diagnostic accuracy across multiple studies 4:
- AUROC of 0.765-0.91 for detecting advanced fibrosis (F3-F4) or cirrhosis, depending on the population studied 4, 3
- Sensitivity of 70-87% at lower cutoff values for excluding advanced fibrosis 2, 5, 3
- Specificity of 87-98% at higher cutoff values for confirming advanced fibrosis 5, 4
The test performs best at ruling out advanced fibrosis (high negative predictive value) rather than confirming it 2.
Important Caveats and Limitations
Age significantly affects FIB-4 values since age is a numerator in the formula, leading to higher false-positive rates in elderly patients (consider using <2.0 as cutoff if age ≥65 years) and potential false-negatives in younger patients 2.
The indeterminate zone (1.3-2.67) captures approximately 30-40% of patients, necessitating additional testing with elastography or other noninvasive tests 2.
FIB-4 has limited accuracy in patients with diabetes and metabolic syndrome in NAFLD populations 2.
Clinical Application Algorithm
When FIB-4 <1.3 (or <2.0 if age ≥65): Advanced fibrosis is unlikely; repeat testing every 1-3 years in at-risk populations 2.
When FIB-4 1.3-2.67: Proceed to liver elastography (FibroScan, VCTE) as second-line test, or implement lifestyle intervention and retest in 1 year 2.
When FIB-4 >2.67: High probability of advanced fibrosis; refer to hepatology for comprehensive evaluation and consider elastography or liver biopsy for confirmation and staging 2.
Monitoring Fibrosis Progression
Serial FIB-4 measurements can track fibrosis progression over time 6. The change in FIB-4 index per year (ΔFIB-4/year) is an independent predictive factor for fibrosis progression, with a cutoff of ≥0.4 per year associated with significantly higher cumulative incidence of progression to cirrhosis (34% at 5 years and 59% at 10 years) compared to <0.4 per year (0% at 5 years and 3% at 10 years) 6.