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

The FIB-4 index is a validated non-invasive biomarker that effectively identifies liver fibrosis severity in chronic liver diseases, with superior diagnostic performance compared to other serum markers, particularly for excluding advanced fibrosis. 1

What is the FIB-4 Index?

The FIB-4 index is a simple, inexpensive blood-based biomarker that calculates liver fibrosis risk using:

Age (years)
AST (aspartate aminotransferase)
ALT (alanine aminotransferase)
Platelet count

The formula is: FIB-4 = (Age × AST) / (Platelets × √ALT) 2

Diagnostic Performance in Different Liver Diseases

Non-Alcoholic Fatty Liver Disease (NAFLD)

FIB-4 <1.3: Low risk of advanced fibrosis (high negative predictive value) 1
FIB-4 >1.3: Requires further evaluation with VCTE (vibration-controlled transient elastography) or referral to hepatologist 1
Age-adjusted cutoffs:
- <65 years: use 1.3 as lower cutoff
- ≥65 years: use 2.0 as lower cutoff (to avoid false positives in elderly) 1
Upper cutoff: 2.67 for diagnosing advanced fibrosis 1

Viral Hepatitis B

FIB-4 <1.45: Excludes significant fibrosis with 86% negative predictive value 3
FIB-4 demonstrates good diagnostic accuracy with AUC of 0.81 for identifying fibrosis stages 3
Performance improves with longer biopsy specimens (AUC up to 0.94 for biopsies ≥20mm) 3

Viral Hepatitis C

FIB-4 <1.45: Excludes advanced fibrosis 1
FIB-4 >3.25: Suggests advanced fibrosis 1
Superior to APRI for diagnosing cirrhosis 1

Clinical Application Algorithm

Initial Screening:
- Calculate FIB-4 in patients with suspected chronic liver disease 1
- Apply disease-specific cutoffs (see above) 1, 2
Interpretation of Results:
- Low FIB-4: Advanced fibrosis unlikely, monitor periodically 1
- Indeterminate/High FIB-4: Proceed to additional testing (VCTE/elastography) 1
Follow-up Recommendations:
- Low-risk patients with metabolic risk factors: Re-evaluate FIB-4 in 1-2 years 1
- Low-risk NAFLD patients without diabetes: Re-evaluate FIB-4 in 2-3 years 1
- High-risk patients: Refer to hepatologist for comprehensive evaluation 1

Advantages and Limitations

Advantages:

Non-invasive alternative to liver biopsy 1
Utilizes routine laboratory tests (cost-effective) 2, 4
High negative predictive value for excluding advanced fibrosis 1, 3
Validated across multiple liver diseases 1, 2

Limitations:

Moderate diagnostic accuracy for positive identification of advanced fibrosis 1
Performance affected by:
- Age (false positives in elderly patients) 1
- Acute inflammation (elevated transaminases) 1
- Limited validation in alcoholic liver disease 2
- Lower accuracy in patients with diabetes 1

Prognostic Value

Beyond diagnosis, FIB-4 has significant prognostic value:

High FIB-4 scores correlate with increased risk of:
- Hepatocellular carcinoma 2, 5
- Liver-related mortality 2, 5
- Esophageal varices (cutoffs 2.87-3.91 in cirrhosis) 2
Even in patients without known chronic liver disease, high-risk FIB-4 scores are associated with severe liver outcomes (HR 4.05) 5

Integration with Other Diagnostic Methods

FIB-4 performs best when combined with other non-invasive tests:

Sequential or simultaneous testing with VCTE improves diagnostic accuracy 1, 4
Combined algorithm: FIB-4 <1.3 and VCTE <8 kPa reliably excludes advanced fibrosis 1
FIB-4 ≥3.48 and VCTE ≥20 kPa reliably diagnoses cirrhosis 1
Positive correlation between FIB-4 and transient elastography measurements (r = 0.401) 6

Common Pitfalls to Avoid

Misinterpreting results in elderly patients (use age-adjusted cutoffs) 1
Relying solely on FIB-4 for diagnosis rather than as a screening tool 1, 2
Applying incorrect cutoffs for specific liver diseases 2, 3
Using FIB-4 during acute hepatitis (false elevations due to inflammation) 1
Overlooking the need for follow-up in patients with indeterminate results 1

What is the Fib 4 index (Fibrosis-4 index) and how is it used to assess liver fibrosis in patients with chronic liver diseases?

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