How to Calculate the Fibrosis-4 (FIB-4) Index
Formula
The FIB-4 index is calculated using the formula: [Age (years) × AST (IU/L)] / [Platelet count (×10⁹/L) × √ALT (IU/L)] 1, 2, 3
Required Laboratory Values
To calculate FIB-4, you need exactly four values 2:
- Age in years
- AST (aspartate aminotransferase) in IU/L or U/L
- ALT (alanine aminotransferase) in IU/L or U/L
- Platelet count in ×10⁹/L (or divide by 1000 if reported as cells/μL)
Step-by-Step Calculation Example
If a patient is 55 years old with AST 60 U/L, ALT 80 U/L, and platelets 150 × 10⁹/L 2:
- Multiply age by AST: 55 × 60 = 3,300
- Calculate square root of ALT: √80 = 8.94
- Multiply platelets by √ALT: 150 × 8.94 = 1,341
- Divide numerator by denominator: 3,300 / 1,341 = 2.46
Interpretation of Results
The FIB-4 score stratifies patients into three risk categories for advanced liver fibrosis 2, 4:
FIB-4 <1.3 (or <1.45): Low probability of advanced fibrosis with approximately 90% negative predictive value—advanced fibrosis is effectively ruled out 2, 3, 4
FIB-4 1.3-2.67 (or 1.45-3.25): Indeterminate range requiring second-tier testing such as transient elastography (FibroScan) or Enhanced Liver Fibrosis (ELF) testing 2, 4
FIB-4 >2.67 (or >3.25): High probability of advanced fibrosis with 60-80% positive predictive value—requires immediate hepatology referral 2, 3, 4
Critical Age-Related Adjustments
Age significantly affects FIB-4 interpretation and requires threshold modifications 2:
- For patients ≥65 years: Use a higher low-risk cutoff of <2.0 instead of <1.3 to reduce false-positive rates that occur naturally with aging 2
- For younger patients: Standard thresholds apply, but be aware of potential false-negatives 2
Clinical Performance Characteristics
The FIB-4 index demonstrates 2, 3:
- AUROC of 0.77-0.86 for detecting advanced fibrosis, depending on the population studied
- Superior performance at ruling out advanced fibrosis (high negative predictive value of 90%) rather than confirming it 2, 3
- At cutoff <1.45, sensitivity of 70% and negative predictive value of 90% for excluding advanced fibrosis 3
- At cutoff >3.25, specificity of 97% and positive predictive value of 65% for advanced fibrosis 3
Important Limitations and Pitfalls
Several factors can compromise FIB-4 accuracy 2, 5:
- Limited accuracy in the indeterminate range (1.3-2.67), where approximately 30-40% of patients fall—these patients absolutely require additional testing with elastography or ELF 2
- Diabetes and metabolic syndrome may reduce diagnostic accuracy in NAFLD populations 2
- Not validated as a standalone tool in cystic fibrosis-associated liver disease—requires combination with transient elastography in CF patients 5
- Acute hepatocellular injury (elevated AST/ALT from acute hepatitis, drug toxicity, or ischemia) will artificially elevate FIB-4 and should not be calculated during acute illness 2
Clinical Action Algorithm Based on FIB-4 Results
When FIB-4 is <1.3 (or <2.0 if age ≥65) 2:
- Advanced fibrosis is unlikely
- Repeat testing every 1-3 years in at-risk populations (chronic liver disease, NAFLD, viral hepatitis)
- No immediate hepatology referral needed
- Proceed to liver elastography (FibroScan/VCTE) as second-line test
- Alternative: Implement 1-year lifestyle intervention and retest FIB-4
- Consider ELF testing if elastography unavailable
When FIB-4 is >2.67 (or >3.25) 2, 4:
- High probability of advanced fibrosis—immediate hepatology referral required
- Consider elastography or liver biopsy for confirmation and precise staging
- Initiate hepatocellular carcinoma surveillance if cirrhosis confirmed
- Aggressive management of underlying liver disease and metabolic risk factors
Monitoring Fibrosis Progression Over Time
Serial FIB-4 measurements can track fibrosis progression 6:
- Calculate ΔFIB-4 index per year (change in FIB-4 divided by time interval in years)
- ΔFIB-4/year ≥0.4 predicts progression to cirrhosis with AUROC of 0.910 6
- Patients with ΔFIB-4/year ≥0.4 have 34% and 59% cumulative incidence of cirrhosis at 5 and 10 years, respectively 6
- Patients with ΔFIB-4/year <0.4 have only 0% and 3% cumulative incidence of cirrhosis at 5 and 10 years 6