FIB-4 Score Calculation Formula
The FIB-4 score is calculated using the formula: Age (years) × AST (IU/L) / [Platelet count (×10⁹/L) × √ALT (IU/L)] 1.
Required Laboratory Values
To calculate FIB-4, you need four specific values:
- Age in years 1
- AST (aspartate aminotransferase) in IU/L or U/L 1
- ALT (alanine aminotransferase) in IU/L or U/L 1
- Platelet count in ×10⁹/L (or multiply by 10⁹ if given in standard units) 1
Step-by-Step Calculation
- Multiply the patient's age by their AST level 1
- Calculate the square root of the ALT value 1
- Multiply the platelet count by the square root of ALT 1
- Divide the result from step 1 by the result from step 3 1
Interpretation of Results
Standard Cutoff Values (Adults <65 years)
- FIB-4 <1.3 (or <1.45): Low probability of advanced fibrosis, with a negative predictive value of approximately 90% for advanced fibrosis 1, 2
- FIB-4 1.3-2.67 (or 1.45-3.25): Indeterminate range requiring additional testing such as elastography or Enhanced Liver Fibrosis (ELF) testing 1
- FIB-4 >2.67 (or >3.25): High probability of advanced fibrosis, with a positive predictive value of approximately 65% for advanced fibrosis 1
Age-Adjusted Cutoffs (≥65 years)
- For patients aged 65 years or older, use a higher threshold of FIB-4 >2.0 instead of >1.3 to reduce false positives, as FIB-4 naturally increases with age 1, 3
Age-Specific Cutoffs for NAFLD (Validated in Japanese Cohort)
- Age ≤49 years: Low cutoff 1.05, high cutoff 1.21 3
- Age 50-59 years: Low cutoff 1.24, high cutoff 1.96 3
- Age 60-69 years: Low cutoff 1.88, high cutoff 2.67 3
- Age ≥70 years: Low cutoff 1.95, high cutoff 2.67 3
Clinical Performance
- FIB-4 has an AUROC of approximately 0.77-0.86 for detecting advanced fibrosis, depending on the population studied 1, 2
- The test performs best at ruling out advanced fibrosis (high negative predictive value) rather than confirming it 1, 2
- FIB-4 may miss approximately 10% of patients with advanced fibrosis even when below the low cutoff 1
- Serial FIB-4 measurements can track fibrosis progression: An increase in FIB-4 of ≥0.4 per year predicts progression to cirrhosis with an AUROC of 0.910 4
Important Limitations
- FIB-4 has limited accuracy in the intermediate range (1.3-2.67), where approximately 30-40% of patients fall, necessitating additional testing 1
- Age significantly affects FIB-4 values: The score naturally increases with age, leading to higher false-positive rates in elderly patients and potential false-negatives in younger patients 1, 3
- Performance varies by underlying liver disease: FIB-4 was originally validated in hepatitis C/HIV co-infection but is now widely used in NAFLD, hepatitis B, and other chronic liver diseases 1, 4
- Diabetes and metabolic syndrome may reduce diagnostic accuracy in NAFLD populations 1
Clinical Application Algorithm
When FIB-4 is <1.3 (or <2.0 if age ≥65):
- Advanced fibrosis is unlikely 1
- Repeat testing every 1-3 years in at-risk populations 1
- No immediate need for elastography or liver biopsy 1
When FIB-4 is 1.3-2.67 (indeterminate):
- Proceed to liver elastography (FibroScan, VCTE) as second-line test 1
- Alternative: Implement 1-year lifestyle intervention and retest; if still elevated, proceed to elastography 1
- Consider ELF testing as alternative to elastography 1
When FIB-4 is >2.67 (or >3.25):