What is the preferred test, Enhanced Liver Fibrosis (ELF) test or NASH Fibrosure plus, for assessing liver fibrosis in patients with suspected non-alcoholic steatohepatitis (NASH) or other chronic liver diseases?

ELF Test vs NASH FibroSure Plus for Liver Fibrosis Assessment

For assessing liver fibrosis in NAFLD/NASH, the Enhanced Liver Fibrosis (ELF) test is the preferred second-line test after FIB-4 screening, as it has superior guideline support and validated diagnostic performance compared to NASH FibroSure Plus, which lacks guideline endorsement and independent validation studies.

Guideline-Recommended Testing Algorithm

The most recent guidelines establish a clear hierarchy for noninvasive fibrosis assessment 1, 2:

• First-line screening: Calculate FIB-4 for all patients with suspected NAFLD or chronic liver disease 1, 2, 3

  • FIB-4 <1.3 (or <2.0 if age ≥65): Low risk, reassess in 2-3 years 1, 2
  • FIB-4 1.3-2.67: Indeterminate zone requiring second-tier testing 1, 2
  • FIB-4 >2.67: High risk, refer to hepatology 1, 2

• Second-line testing for indeterminate FIB-4: Use ELF test, transient elastography (TE), or MR elastography 1, 2

Why ELF Test is Preferred Over NASH FibroSure Plus

Guideline Support for ELF

ELF is explicitly recommended in multiple major society guidelines, while NASH FibroSure Plus has no guideline endorsement:

• The European Association for the Study of the Liver (EASL) 2021 guidelines specifically recommend ELF™ <9.8 to rule out advanced fibrosis and list it among validated patented tests 1
• The American Association for the Study of Liver Diseases (AASLD) 2018 guidance identifies ELF panel as one of the commonly investigated noninvasive tools for advanced fibrosis 1
• The American Gastroenterological Association 2022 update recommends ELF as a confirmatory prognostic test in lean NAFLD patients 1
• The Korean Association for the Study of the Liver (KASL) 2013 guidelines note ELF showed favorable results with AUROC 0.90, sensitivity 80%, and specificity 90% for advanced fibrosis 1

Diagnostic Performance of ELF

ELF demonstrates excellent and well-validated diagnostic accuracy:

• Meta-analysis of 11 studies (4,452 patients) showed ELF has AUROC 0.83 for detecting advanced fibrosis 1
• ELF achieves sensitivity >90% at low cut-off of 7.7 for excluding fibrosis 4
• At high cut-off of 9.8-10.18, ELF achieves specificity 0.86-0.90 for diagnosing advanced fibrosis 1, 4
• Direct comparison study showed ELF had AUROC 0.90 for advanced fibrosis with 89.8% sensitivity and 85.5% specificity 5, 6

Clinical Utility and Prognostic Value

ELF provides both diagnostic and prognostic information:

• Baseline ELF scores predict disease progression: patients with F3 disease who progressed to cirrhosis had higher baseline ELF scores 7
• Changes in ELF over time correlate with clinical outcomes: increases in ELF associated with increased risk of progression in both F3 and F4 patients 7
• ELF scores ≥11.27 are associated with significantly increased risk of hepatic decompensation and hepatocellular carcinoma 3
• Higher ELF scores (≥10.43) correlate with impaired patient-reported outcomes 7

Cost-Effectiveness

Sequential FIB-4 followed by ELF is cost-effective:

• This approach reduces unnecessary liver biopsies and specialist referrals while maintaining high diagnostic accuracy 3
• Cost-benefit analyses support sequential strategies using ELF in alcohol-related liver disease, which extends to NAFLD 3

Absence of Evidence for NASH FibroSure Plus

NASH FibroSure Plus lacks the validation and guideline support necessary for clinical recommendation:

• No major hepatology society guidelines (AASLD, EASL, KASL, AGA) mention or recommend NASH FibroSure Plus
• No independent validation studies or meta-analyses establish its diagnostic performance
• No published data comparing NASH FibroSure Plus head-to-head with ELF or other validated tests
• The proprietary nature without transparent validation limits clinical adoption

Practical Implementation Strategy

Use this sequential approach for optimal fibrosis assessment 1, 2, 3:

1. Calculate FIB-4 first using age, AST, ALT, and platelet count
2. If FIB-4 is indeterminate (1.3-2.67), proceed to ELF testing
3. Interpret ELF results:
   • ELF <7.7: Low risk, continue primary care with lifestyle modifications
   • ELF 7.7-9.8: Intermediate risk, consider TE or repeat testing in 6-12 months
   • ELF ≥9.8: High risk for advanced fibrosis, refer to hepatology 1, 8

Important Caveats

Be aware of these limitations when using ELF:

• ELF has lower positive predictive value in low-prevalence settings (<50% prevalence), so additional testing may be needed to confirm positive results 4
• ELF performs best for excluding rather than confirming advanced fibrosis, similar to other noninvasive tests 4
• Age affects FIB-4 accuracy: use higher cut-offs (FIB-4 <2.0) for patients ≥65 years before proceeding to ELF 1, 3
• Combining ELF with TE increases specificity to 97.9% when both are positive, reducing false positives 6

When to Consider Alternative Testing

If ELF is unavailable or results are discordant with clinical suspicion:

• Proceed directly to vibration-controlled transient elastography (VCTE/FibroScan) with cut-offs: <8 kPa rules out advanced fibrosis, ≥12 kPa suggests advanced fibrosis 1
• Consider MR elastography as the most accurate noninvasive method, though it is more expensive and suited for clinical trials rather than first-line use 1
• Liver biopsy remains indicated when noninvasive tests are indeterminate, concurrent liver diseases cannot be excluded, or treatment decisions require histologic confirmation 1