Enhanced Liver Fibrosis (ELF) Score: A Biomarker Panel for Liver Fibrosis Assessment
The Enhanced Liver Fibrosis (ELF) score is a validated serum biomarker panel that measures three matrix turnover proteins to accurately assess liver fibrosis severity, with an area under the receiver operating curve (AUROC) of 0.90 for detecting advanced fibrosis in patients with chronic liver disease. 1
Components of the ELF Score
The ELF score consists of three specific extracellular matrix proteins involved in liver fibrosis:
- Hyaluronic acid (HA)
- Tissue inhibitor of metalloproteinase 1 (TIMP-1)
- N-terminal propeptide of type III procollagen (PIIINP)
These components are measured in serum and combined using a proprietary algorithm to generate a single numerical score.
Clinical Utility and Performance
The ELF score has demonstrated excellent diagnostic accuracy for liver fibrosis:
- For advanced fibrosis (≥F3): AUROC of 0.90 with 80% sensitivity and 90% specificity using a cutoff value of 0.3576 1
- For significant fibrosis (≥F2): AUROC of 0.82 using a cutoff value of >-0.1068 1
Established Cutoff Values
Based on clinical validation studies, the following cutoff values are recommended 2:
- <7.7: Low probability of fibrosis (high sensitivity for exclusion)
- 9.8-11.3: High probability of advanced fibrosis
- ≥11.3: Cirrhosis (sensitivity 83%, specificity 97%)
Prognostic Value
The ELF score provides valuable prognostic information beyond simple fibrosis staging:
- Patients with ELF scores ≥9.8 have significantly higher risk of liver-related clinical outcomes 3
- Each unit increase in ELF score is associated with a 2.53-fold increased risk of liver-related events 3
- ELF scores ≥13 indicate particularly high risk, with 26% developing hepatic decompensation within 90 days and 38% all-cause mortality at 1 year 4
Clinical Application in NAFLD/NASH
The ELF score is particularly useful in the assessment of nonalcoholic fatty liver disease (NAFLD):
- It can be used as part of a sequential testing strategy after initial screening with simpler tests like FIB-4 1
- When used as a second-line test after FIB-4, it can reduce specialist referrals by up to 34% 4
- It outperforms FIB-4 for predicting liver-related mortality, particularly in the short term 4
Advantages and Limitations
Advantages:
- Non-invasive alternative to liver biopsy
- Commercially available (primarily in Europe)
- High diagnostic accuracy for advanced fibrosis
- Provides prognostic information beyond simple staging
Limitations:
- Influenced by age and gender (reference ranges are higher in men and increase with age) 2
- May be affected by inflammatory processes, not just fibrosis 5
- Less discriminative in low to moderate fibrosis stages 5
- Not widely available in all countries (including limited availability in the United States) 1
Comparison to Other Non-invasive Tests
When compared to other non-invasive tests for liver fibrosis:
- ELF generally shows similar or better performance than FIB-4 and NAFLD Fibrosis Score for advanced fibrosis 1
- Vibration-controlled transient elastography (VCTE/FibroScan) and magnetic resonance elastography (MRE) may be used as complementary tests 1
- Sequential testing using ELF after FIB-4 improves diagnostic accuracy and reduces indeterminate results 1
Clinical Implementation
For optimal use in clinical practice:
- Consider using ELF as part of a stepwise approach after initial screening with simpler tests like FIB-4
- Account for age and gender when interpreting results
- Use established cutoff values for risk stratification
- Consider additional testing (elastography or biopsy) for indeterminate results
- Recognize the prognostic value for identifying patients at high risk of clinical outcomes
The ELF score represents an important advance in non-invasive assessment of liver fibrosis that can help identify patients at risk for disease progression and adverse outcomes.