What is a Fib-4 (Fibrosis-4) score in the context of liver disease?

What is the FIB-4 Score?

The FIB-4 (Fibrosis-4) score is a simple, validated blood-based calculator that uses four readily available laboratory values—age, AST, ALT, and platelet count—to noninvasively assess the risk of advanced liver fibrosis in patients with chronic liver disease. 1

Calculation and Components

The FIB-4 formula is: (Age × AST) / (Platelet count × √ALT) 1, 2

• This calculation requires only routine laboratory values that are typically available in any clinical setting, making it cost-free and universally accessible 1
• No proprietary testing or specialized equipment is needed 1

Primary Clinical Purpose

FIB-4 serves as the recommended first-line screening tool to identify patients at low or high probability of advanced liver fibrosis, helping determine who needs further evaluation or specialist referral. 1

• The score performs best at ruling out advanced fibrosis rather than confirming it, with negative predictive values exceeding 90% at appropriate cutoffs 1
• It is the most validated noninvasive test for this purpose according to major hepatology societies 1

Risk Stratification Cutoffs

For NAFLD/Metabolic Liver Disease:

• FIB-4 <1.3 (or <2.0 if age ≥65 years): Low risk - reliably excludes advanced fibrosis; reassess in 2-3 years 3, 1
• FIB-4 1.3-2.67: Indeterminate zone - requires secondary testing with elastography (FibroScan) or Enhanced Liver Fibrosis (ELF) test 1
• FIB-4 >2.67: High risk - indicates high probability of advanced fibrosis; warrants immediate hepatology referral 1

Age-Adjusted Considerations:

Always use the higher cutoff (<2.0) for patients ≥65 years to avoid overestimating fibrosis risk, as age is a major driver of the FIB-4 calculation. 1, 4

• FIB-4 performs poorly in patients younger than 35 years and requires adjusted interpretation in those ≥65 years 1

Clinical Implementation Algorithm

Step 1: Initial Screening

Calculate FIB-4 for all patients with:

• NAFLD or metabolic syndrome 1
• Type 2 diabetes 1
• Chronic viral hepatitis 1
• Unexplained elevated liver enzymes 1

Step 2: Risk-Based Management

Low-risk patients (FIB-4 <1.3 or <2.0 if ≥65 years):

• Continue primary care management with lifestyle modifications 1
• Reassess with repeat FIB-4 in 2-3 years 3, 1
• No hepatology referral needed unless clinical deterioration occurs 1

Indeterminate-risk patients (FIB-4 1.3-2.67):

• Perform secondary testing with vibration-controlled transient elastography (VCTE/FibroScan) or ELF test 1
• If VCTE ≥12 kPa or ELF ≥9.8, refer to hepatology 1

High-risk patients (FIB-4 >2.67):

• Immediate hepatology referral for comprehensive evaluation 1
• Consider liver biopsy or magnetic resonance elastography (MRE) 1
• Initiate hepatocellular carcinoma surveillance if cirrhosis confirmed 1

Prognostic Value Beyond Diagnosis

Elevated FIB-4 scores are strongly associated with future liver-related complications, including hepatocellular carcinoma, liver decompensation, liver transplantation, and death. 1

• Sequential FIB-4 measurements provide prognostic value: increasing scores over time indicate worsening fibrosis risk and higher mortality 5
• FIB-4 predicts not only liver outcomes but also cardiovascular events and all-cause mortality in patients with metabolic disease 5, 6

Disease-Specific Performance

Strong Performance:

• Chronic hepatitis C: AUROC 0.84 for cirrhosis, with cutoffs of 1.45 and 3.25 1, 7
• Chronic hepatitis B: Cutoffs of 1.0 and 2.65 for advanced fibrosis 7
• NAFLD: Well-validated with cutoffs of 1.3 and 2.67 3, 1

Lower Accuracy:

• Alcoholic liver disease: Low-to-moderate accuracy; consider alternative testing 1, 7
• Autoimmune hepatitis: Suboptimal performance 7
• NAFLD with type 2 diabetes: Diagnostic performance may be reduced 3

Important Limitations and Caveats

FIB-4 has only moderate positive predictive value (60-80%) for confirming advanced disease, meaning elevated scores require confirmation with secondary testing. 1

• The score can be falsely elevated by factors unrelated to fibrosis: advanced age, elevated AST from non-hepatic causes, or thrombocytopenia from other conditions 1, 4
• In population-based screening, FIB-4 has a non-negligible false-negative rate (up to 43% in some studies), particularly in at-risk patients with diabetes or obesity 8
• FIB-4 should not be used as the sole basis for initiating antiviral therapy in chronic hepatitis B, as there is insufficient evidence for this application 3

Comparison to Other Noninvasive Tests

• FIB-4 outperforms APRI (AST-to-Platelet Ratio Index) for detecting both significant and advanced fibrosis 1
• FIB-4 is recommended as first-line due to simplicity and zero cost, though proprietary tests like ELF or imaging-based elastography may have superior accuracy 1
• Sequential testing (FIB-4 followed by ELF or VCTE for indeterminate results) is cost-effective and reduces unnecessary liver biopsies 1

Common Pitfalls to Avoid

• Do not pursue invasive testing or specialist referral based solely on imaging findings (e.g., coarsened liver echotexture on ultrasound) when FIB-4 is reassuringly low 1
• Do not use standard cutoffs in patients ≥65 years—always apply the higher threshold of 2.0 instead of 1.3 3, 1
• Do not interpret FIB-4 in isolation—consider clinical context, including presence of metabolic risk factors, alcohol use, and other liver disease etiologies 3, 1
• Do not assume a single elevated FIB-4 confirms cirrhosis—secondary testing is mandatory for confirmation 1