FIB-4 Index with Reflex to Enhanced Liver Fibrosis (ELF) Score
For patients undergoing evaluation for liver fibrosis, use FIB-4 as the first-line screening test, then reflex to ELF testing for those with indeterminate FIB-4 scores (1.3-3.25 for age <65 years, or 1.3-2.0 for age ≥65 years) to accurately identify advanced fibrosis and reduce unnecessary referrals and liver biopsies. 1
Initial Assessment with FIB-4
Calculate FIB-4 for all patients with suspected NAFLD or chronic liver disease using the formula: (age × AST)/(platelets × √ALT). 1
FIB-4 Interpretation by Age:
For patients <65 years old: 1
- FIB-4 <1.3: Low risk for advanced fibrosis—manage in primary care with lifestyle modifications and reassess in 2-3 years
- FIB-4 1.3-3.25: Indeterminate risk—proceed to ELF testing (reflex testing)
- FIB-4 >3.25: High risk—refer to hepatology for comprehensive evaluation
For patients ≥65 years old: 1
- FIB-4 <2.0: Low risk—manage in primary care
- FIB-4 ≥2.0: Proceed to ELF testing or hepatology referral
Reflex to ELF Testing
When FIB-4 falls in the indeterminate range, automatically perform ELF testing to improve diagnostic accuracy and reduce unnecessary specialist referrals. 1, 2
ELF Score Interpretation:
ELF <7.7: Low risk for advanced fibrosis—continue primary care management with serial monitoring 1
ELF 7.7-9.8: Intermediate risk—consider vibration-controlled transient elastography (VCTE) or refer to hepatology if discordant with clinical picture 1, 2
ELF ≥9.8: High risk for advanced fibrosis—immediate hepatology referral for comprehensive evaluation, including consideration of liver biopsy, hepatocellular carcinoma surveillance, and variceal screening 1, 2
ELF >11.3: Strongly suggests cirrhosis—urgent hepatology referral for cirrhosis-based management 1, 3
Diagnostic Performance
The sequential FIB-4-to-ELF approach demonstrates superior diagnostic accuracy compared to FIB-4 alone. In real-world MASLD cohorts, this two-step strategy showed 67.86% sensitivity, 90.40% specificity, 75.18% positive predictive value, and 86.78% negative predictive value for advanced fibrosis. 2
ELF testing maintains an AUROC of 0.829-0.90 for detecting advanced fibrosis in NAFLD/MASLD, outperforming FIB-4 (AUROC 0.769-0.82) and NAFLD Fibrosis Score (AUROC 0.699-0.80). 2, 4, 5
Clinical Benefits of the Sequential Approach
This two-step strategy reduces unnecessary liver biopsies by 71.8% while maintaining diagnostic accuracy, making it particularly valuable in primary care settings where advanced imaging may not be readily available. 2
The approach reduces specialist referrals by 12.5-15.8% and lowers healthcare costs by identifying truly high-risk patients who require tertiary care evaluation. 6
Important Caveats
FIB-4 has reduced accuracy in patients <35 years old due to age-dependent calculations, and adjusted cutoffs are necessary for those ≥65 years to avoid overestimating fibrosis risk. 1, 7
FIB-4 performs poorly in alcoholic liver disease and autoimmune hepatitis compared to viral hepatitis and NAFLD, so consider alternative testing strategies in these populations. 7
ELF testing requires specialized laboratory capabilities for measuring hyaluronic acid, TIMP-1, and PIIINP, which may not be available in all primary care settings. 5
When to Consider Alternative Testing
If ELF testing is unavailable or results are discordant with clinical suspicion, proceed directly to VCTE (FibroScan) or magnetic resonance elastography (MRE) for liver stiffness measurement. 1
VCTE cutoffs for advanced fibrosis: ≥8.0-12.0 kPa suggests significant fibrosis; ≥12.0 kPa suggests advanced fibrosis; ≥15.0 kPa suggests cirrhosis; ≥20-25 kPa suggests clinically significant portal hypertension. 1
Management Based on Results
For low-risk patients (low FIB-4 or low ELF): Implement lifestyle modifications targeting 7-10% weight loss, 150-300 minutes weekly moderate-intensity exercise, and address metabolic risk factors. Reassess with FIB-4 every 2-3 years. 1
For high-risk patients (high FIB-4 and high ELF): Immediate hepatology referral for initiation of hepatocellular carcinoma surveillance (ultrasound ±AFP every 6 months), variceal screening via upper endoscopy, consideration of pharmacotherapy (vitamin E, GLP-1 receptor agonists, or pioglitazone), and aggressive cardiovascular risk management. 1, 3, 8