What tests are part of a non-invasive liver screen?

Non-Invasive Liver Fibrosis Assessment Tests

A comprehensive non-invasive liver screen should include both serum biomarkers and physical measurement of liver stiffness, with transient elastography (TE) being the preferred physical assessment method when available. 1

Types of Non-Invasive Tests

Non-invasive methods for assessing liver fibrosis fall into two main categories:

1. Biological Approach (Serum Biomarkers)

Basic Laboratory Tests

• AST (aspartate aminotransferase)
• ALT (alanine aminotransferase)
• Platelet count
• Total bilirubin
• Albumin
• Prothrombin time/INR
• GGT (gamma-glutamyl transpeptidase)

These parameters should be part of routine investigations in patients with suspected liver disease to enable calculation of simple non-invasive scores 1.

Serum-Based Fibrosis Scores

• FIB-4: Age (years) × AST [U/L]/(platelets [10⁹/L] × (ALT [U/L])½)
  • Simpler to calculate and performs better than other simple NITs, particularly in NAFLD 1
• APRI (AST to Platelet Ratio Index): AST (/ULN)/platelet (10⁹/L) × 100
• AST/ALT ratio (AAR)
• Forns Index: 7.811 - 3.131 × ln(platelet count) + 0.781 × ln(GGT) + 3.467 × ln(age) - 0.014 × (cholesterol)
• NAFLD Fibrosis Score (for NAFLD patients)

Patented Serum Biomarkers

• FibroTest®: Combines α-2-macroglobulin, γGT, apolipoprotein A1, haptoglobin, total bilirubin, age and gender
• FibroMeter®: Combines platelet count, prothrombin index, AST, α-2-macroglobulin, hyaluronate, urea and age
• Enhanced Liver Fibrosis score® (ELF): Combines age, hyaluronate, MMP-3 and TIMP-1
• Hepascore®: Combines bilirubin, γGT, hyaluronate, α-2-macroglobulin, age and gender

2. Physical Approach (Elastography)

• Transient Elastography (TE/FibroScan®): Measures liver stiffness through mechanical waves
  • Most widely validated non-invasive assessment for liver fibrosis 2
  • High accuracy for detecting advanced fibrosis and cirrhosis
• Acoustic Radiation Force Impulse (ARFI)
• Shear Wave Elastography (SWE)
• Magnetic Resonance Elastography (MRE)

Recommended Testing Algorithm

1. First-line screening (particularly in primary care):

   • Calculate simple non-invasive scores (FIB-4 recommended) using routine laboratory tests (AST, ALT, platelet count) 1
   • These tests should be used to rule out rather than diagnose advanced fibrosis in low-prevalence populations

2. Second-line assessment (for indeterminate or high-risk results):

   • Transient elastography (TE) when available
   • Patented serum biomarkers when TE is not available

3. Combined approach:

   • Combining TE with serum biomarkers increases diagnostic accuracy
   • Concordance between tests increases reliability of the results

Disease-Specific Considerations

Hepatitis C

• All HCV patients should be screened to exclude cirrhosis by TE if available
• Serum biomarkers can be used in the absence of TE 1
• Patients diagnosed with cirrhosis based on non-invasive tests should undergo screening for hepatocellular carcinoma (HCC) and portal hypertension

Hepatitis B

• TE generally has higher accuracy compared to serum biomarkers for advanced liver fibrosis 1
• LS <5-6 kPa often indicates absent or minimal liver fibrosis
• LS >12-14 kPa often indicates liver cirrhosis
• Caution needed when interpreting TE results in patients with elevated ALT levels

NAFLD/MAFLD

• FIB-4 performs well as an initial screening tool
• TE is particularly useful for detecting advanced fibrosis

Important Caveats and Pitfalls

• ALT fluctuations: Elevated ALT can falsely increase liver stiffness measurements; interpretation should be cautious in patients with acute hepatitis or ALT flares 1

• Spectrum effect: Non-invasive tests have lower sensitivity and higher specificity when applied in populations with lower disease prevalence 1

• Indeterminate results: When non-invasive tests yield indeterminate results or show discordance, liver biopsy may still be necessary 1

• Test limitations: Simple fibrosis scores include indirect markers of liver damage and are not direct markers of liver fibrosis; they should not be used as singular decision tools 1

• Population selection: Non-invasive fibrosis tests should be preferentially used in patients at risk of advanced liver fibrosis (such as those with metabolic risk factors and/or harmful alcohol use) and not in unselected general populations 1

By implementing this structured approach to non-invasive liver fibrosis assessment, clinicians can effectively stratify patients according to their risk of significant liver disease while minimizing the need for invasive liver biopsies.