What is FIB-4 (Fibrosis-4)?

FIB-4 (Fibrosis-4 Index): A Non-Invasive Tool for Liver Fibrosis Assessment

FIB-4 is a non-invasive scoring system used to assess liver fibrosis that combines four parameters: age, AST (aspartate aminotransferase), ALT (alanine aminotransferase), and platelet count. It serves as a valuable first-line screening tool to identify patients with advanced liver fibrosis, particularly in those with chronic liver diseases such as NAFLD, viral hepatitis, and other liver conditions 1.

Formula and Calculation

The FIB-4 index is calculated using the following formula:

FIB-4 = (Age × AST) / (Platelets × √ALT)

Where:

• Age is in years
• AST and ALT are in U/L
• Platelet count is in 10^9/L

Clinical Interpretation and Cut-off Values

The interpretation of FIB-4 scores varies by liver disease etiology:

For NAFLD/MASLD:

• <1.30 (for age <65 years) or **<2.0** (for age >65 years): Low risk of advanced fibrosis (90% accuracy for exclusion) 1
• 1.30-2.67: Indeterminate risk, requiring additional testing
• >2.67: High risk of advanced fibrosis (80% accuracy for diagnosis) 1

For Hepatitis C:

• <1.45: Low risk of advanced fibrosis (negative predictive value 94.7%)
• 1.45-3.25: Indeterminate risk
• >3.25: High risk of advanced fibrosis (positive predictive value 82.1%) 2

For Hepatitis B:

• <1.0: Low risk of advanced fibrosis
• >2.65: High risk of advanced fibrosis 3

Clinical Applications

FIB-4 has several important clinical applications:

1. Screening Tool: Particularly valuable in primary care settings to identify patients who need further evaluation 4

2. Risk Stratification: Helps determine which patients should:

   • Be managed in primary care (low FIB-4)
   • Undergo additional testing (indeterminate FIB-4)
   • Be referred to specialists (high FIB-4) 1

3. Monitoring Disease Progression: Sequential measurements can track fibrosis progression over time 5

4. Prognostic Value: Predicts liver-related outcomes, cardiovascular events, and all-cause mortality 6

Advantages and Limitations

Advantages:

• Simple to calculate
• Uses routine laboratory parameters
• Cost-effective
• Non-invasive
• Good negative predictive value for excluding advanced fibrosis
• Can be automatically calculated when liver blood tests are ordered 1

Limitations:

• Moderate accuracy in the indeterminate range
• Less accurate in elderly patients (requires different cut-offs)
• Variable performance across different liver diseases (performs better in NAFLD and viral hepatitis than in alcoholic liver disease) 3
• Not a direct marker of liver fibrosis (includes indirect markers of liver damage) 1

Clinical Algorithm for FIB-4 Use

1. Initial Assessment: Calculate FIB-4 in patients with risk factors for liver disease (metabolic syndrome, diabetes, obesity, viral hepatitis)

2. Risk Stratification:

   • Low FIB-4: Reassurance and lifestyle modification; repeat FIB-4 in 1-3 years if risk factors persist 1
   • Indeterminate FIB-4: Proceed to second-line tests (transient elastography/FibroScan, ELF test, or other imaging modalities) 1
   • High FIB-4: Consider referral to hepatology for advanced fibrosis management 1

3. Sequential Monitoring: Changes in FIB-4 over time provide valuable prognostic information; an increase in FIB-4 suggests progression of liver fibrosis 5, 6

Important Considerations

• FIB-4 should not be used as a singular decision tool; clinical judgment remains essential 1
• For optimal accuracy, FIB-4 should be applied to populations with risk factors for liver disease rather than unselected populations 1
• In patients with indeterminate results, additional testing with more advanced non-invasive methods or liver biopsy may be necessary 1
• AST should be routinely included in liver blood test panels to enable FIB-4 calculation 1

FIB-4 represents an important advancement in non-invasive liver fibrosis assessment, allowing for better risk stratification and potentially reducing the need for liver biopsies in many patients.