What is the FIB-4 (Fibrosis-4) score used for?

What is the FIB-4 Score Used For?

The FIB-4 (Fibrosis-4) score is a simple, validated blood-based calculator used to noninvasively assess the risk of advanced liver fibrosis (scarring) in patients with chronic liver disease, serving as a first-line screening tool to identify who needs further evaluation or specialist referral. 1

Primary Clinical Applications

Risk Stratification for Liver Fibrosis

• FIB-4 is the most validated and recommended first-line noninvasive test for identifying patients at low or high probability of advanced fibrosis (stages F3-F4) in chronic liver disease. 1
• The score uses four readily available laboratory values: age, AST (aspartate aminotransferase), ALT (alanine aminotransferase), and platelet count—making it simple, inexpensive, and accessible in any clinical setting. 1
• It performs best at ruling out advanced fibrosis rather than confirming it, with negative predictive values exceeding 90% at appropriate cutoffs. 1

Disease-Specific Cutoff Values

For NAFLD/Metabolic Dysfunction-Associated Steatotic Liver Disease:

• FIB-4 <1.3 (or <2.0 if age ≥65 years) reliably excludes advanced fibrosis and these patients can be reassessed in 2-3 years. 1
• FIB-4 1.3-2.67 represents an indeterminate zone requiring secondary testing with elastography or enhanced liver fibrosis (ELF) testing. 1
• FIB-4 >2.67 indicates high risk for advanced fibrosis and warrants hepatology referral for further evaluation. 1

For Chronic Hepatitis C:

• FIB-4 <1.45 excludes advanced fibrosis. 1, 2
• FIB-4 >3.25 suggests high probability of advanced fibrosis. 1, 2

For Chronic Hepatitis B:

• FIB-4 <1.0 excludes advanced fibrosis. 2
• FIB-4 >2.65 suggests advanced fibrosis. 2

Prognostic Value Beyond Diagnosis

Predicting Clinical Outcomes

• Elevated FIB-4 scores are strongly associated with future liver-related complications including hepatocellular carcinoma, liver decompensation, liver transplantation, and death—not just fibrosis stage. 1, 3
• High-risk FIB-4 scores (>2.67) carry a 6-7 fold increased hazard of severe liver outcomes even in patients without previously diagnosed chronic liver disease. 3, 4
• In patients with obesity and/or type 2 diabetes, high FIB-4 is associated with 15% cumulative incidence of liver events at 10 years, compared to only 1% in the low-risk group. 4

Monitoring Disease Progression

• Serial FIB-4 measurements provide valuable prognostic information: increases in FIB-4 over time indicate worsening fibrosis risk and higher likelihood of adverse outcomes. 4
• Patients showing a one-unit increase in FIB-4 at 12 months have more than 24-fold increased risk of liver events compared to those with stable low scores. 4

Clinical Implementation Algorithm

Step 1: Calculate FIB-4 in At-Risk Populations

• All patients with NAFLD, metabolic syndrome, type 2 diabetes, chronic viral hepatitis, or unexplained elevated liver enzymes should have FIB-4 calculated. 1

Step 2: Interpret Based on Risk Category

• Low risk (<1.3 for age <65, or <2.0 for age ≥65): Reassess in 2-3 years; no immediate further workup needed. 1
• Indeterminate risk (1.3-2.67): Proceed to secondary testing with vibration-controlled transient elastography (VCTE/FibroScan), shear wave elastography, magnetic resonance elastography, or ELF test. 1
• High risk (>2.67): Refer to hepatology for confirmation with elastography or liver biopsy and initiate surveillance for complications. 1

Step 3: Initiate Appropriate Surveillance

• Patients confirmed to have advanced fibrosis (F3) or cirrhosis (F4) require hepatocellular carcinoma screening and variceal screening per established criteria. 1

Important Limitations and Caveats

Age-Related Performance Issues

• FIB-4 performs poorly in patients younger than 35 years (overestimates fibrosis) and may require adjusted cutoffs in those ≥65 years (underestimates fibrosis). 1, 5
• The age component in the FIB-4 formula means scores naturally increase with age independent of fibrosis progression. 1

Disease-Specific Accuracy

• FIB-4 has lower accuracy in alcoholic liver disease and autoimmune hepatitis compared to viral hepatitis and NAFLD. 2
• In patients with NAFLD accompanied by obesity or elevated ALT, increasing severity of steatosis may decrease FIB-4 diagnostic performance. 1

Screening vs. Diagnostic Tool

• While FIB-4 is excellent for excluding advanced fibrosis (high negative predictive value), it has only moderate positive predictive value (60-80%) for confirming advanced disease. 1
• Population-based studies show FIB-4 can miss up to 43% of patients with elevated liver stiffness ≥8 kPa, particularly in at-risk populations with diabetes or obesity. 6
• False-positive rates of 28-29% occur in both general and at-risk populations, leading to potential overdiagnosis. 6

When FIB-4 is Insufficient

• Discordant results between FIB-4 and secondary tests (elastography, ELF) should prompt consideration of liver biopsy for definitive staging. 1, 5
• FIB-4 cannot assess disease activity (inflammation) or distinguish between different fibrosis stages within the F0-F2 range. 1

Comparison to Other Noninvasive Tests

• FIB-4 outperforms APRI (AST-to-platelet ratio index) for detecting both F2-F4 and F3-F4 fibrosis stages. 1
• While FIB-4 doesn't outperform proprietary tests like ELF, FibroTest, or imaging-based elastography, it is recommended as first-line due to simplicity and zero cost. 1
• Sequential testing (FIB-4 followed by elastography for indeterminate scores) is more accurate than using either test alone. 1