How is an Enhanced Liver Fibrosis (ELF) test score calculated to determine the F score (Fibrosis score)?

How to Calculate the Enhanced Liver Fibrosis (ELF) Score

ELF Score Calculation Formula

The ELF score is calculated using an automated logarithmic algorithm that combines three serum markers of extracellular matrix metabolism: hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), and amino-terminal propeptide of type III procollagen (PIIINP). 1

The specific formula is:

• ELF score = 2.494 + 0.846 × ln(HA) + 0.735 × ln(PIIINP) + 0.391 × ln(TIMP-1) 2

Where:

• HA is measured in ng/mL
• PIIINP is measured in ng/mL
• TIMP-1 is measured in ng/mL
• ln = natural logarithm 2, 3

Relationship Between ELF Score and Fibrosis Stage (F Score)

The ELF score does not directly convert to a specific F stage (F0-F4), but rather provides probability ranges for different degrees of fibrosis. 4, 2

ELF Score Ranges by Fibrosis Stage

Based on validated studies, median ELF scores correspond to histologic fibrosis stages as follows:

• F0 (no fibrosis): ELF score 8.7 (range 8.2-9.2) 4
• F1 (mild fibrosis): ELF score 9.3 (range 8.8-10.0) 4
• F2 (moderate/significant fibrosis): ELF score 10.1 (range 9.4-10.7) 4
• F3 (advanced fibrosis): ELF score 10.7 (range 9.9-11.2) 4
• F4 (cirrhosis): ELF score 12.0 (range 11.2-12.7) 4

Clinical Interpretation Cut-offs

For clinical decision-making, specific ELF cut-off values have been validated to rule out or rule in advanced fibrosis: 2, 5

High Sensitivity Cut-off (Rule-Out)

• ELF < 7.7: Excludes fibrosis with high sensitivity 2
• ELF < 9.34: Excludes advanced fibrosis (≥F3) with 90.4% sensitivity 5

Intermediate Range

• ELF 7.7-9.8: Indeterminate range requiring additional testing 2
• ELF 9.34-10.83: Intermediate probability of advanced fibrosis 5

High Specificity Cut-off (Rule-In)

• ELF ≥ 9.8: Identifies moderate fibrosis (≥F2) with 98% specificity and 69% sensitivity 2
• ELF ≥ 10.83: Identifies advanced fibrosis (≥F3) with 90.6% specificity 5
• ELF ≥ 11.3: Discriminates cirrhosis (F4) with 83% sensitivity and 97% specificity 2

Diagnostic Performance

The ELF test demonstrates superior performance for advanced fibrosis compared to simple fibrosis scores: 1, 4

• For advanced fibrosis (≥F3): AUROC 0.90 with sensitivity 80%, specificity 90%, PPV 71%, NPV 94% 1
• For cirrhosis (F4): Higher diagnostic accuracy than FIB-4 4
• Comparable performance to liver stiffness measurement (FibroScan) with AUROC 0.81-0.84 5

Important Clinical Considerations

Advantages Over FIB-4

• ELF score is not significantly affected by age, unlike FIB-4 which increases with age and requires different cut-offs for patients ≥65 years 4, 2
• Gender differences exist: Men have slightly higher reference values (7.0-9.9) compared to women (6.6-9.3) 2

When to Use ELF Testing

Guidelines recommend ELF as a second-line test when FIB-4 is in the indeterminate range (1.3-2.67 for NAFLD/MASLD or 1.3-3.25 for other etiologies). 1

Sequential Testing Strategy

• Step 1: Calculate FIB-4 as initial screening 1
• Step 2: If FIB-4 is indeterminate, obtain ELF score 1
• Step 3: If ELF ≥10.83, refer to hepatology for advanced fibrosis management 6, 5

Combined Testing Improves Accuracy

• ELF (cut-off 10.83) + LSM (cut-off 11.45 kPa): Increases specificity to 97.9% 5
• Sequential FIB-4 (cut-off 2.67) then ELF (cut-off 9.34): Increases sensitivity to 95.9% 5

Reference Range for Healthy Individuals

Normal ELF score range in healthy controls: 6.7-9.8 2

This represents the upper limit of normal, above which fibrosis should be suspected 2