What laboratory tests are recommended for the diagnosis and management of fatty liver disease?

Laboratory Tests for Fatty Liver Disease Diagnosis and Management

For diagnosis and management of fatty liver disease, initial laboratory evaluation should include bilirubin, albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT), together with a full blood count. 1

Initial Diagnostic Evaluation

First-Line Laboratory Tests

• Liver Function Tests:

  • ALT and AST (most commonly mildly elevated with AST:ALT ratio <1 in early NAFLD) 1, 2
  • Alkaline phosphatase (usually normal or mildly elevated, typically <2× ULN) 2
  • GGT (may range from normal to significantly elevated) 2
  • Bilirubin (typically normal until advanced disease) 2
  • Albumin (to assess synthetic function) 1

• Complete Blood Count:

  • Platelet count (decreased platelets may indicate advanced fibrosis) 1

Exclusion of Other Liver Diseases

A standard liver etiology screen should include 1:

• Hepatitis B surface antigen
• Hepatitis C antibody (with follow-on PCR if positive)
• Anti-mitochondrial antibody
• Anti-smooth muscle antibody
• Antinuclear antibody
• Serum immunoglobulins
• Serum ferritin and transferrin saturation (simultaneously)

Fibrosis Assessment

Non-Invasive Fibrosis Markers

After confirming fatty liver disease and excluding other etiologies, fibrosis assessment is critical as it predicts outcomes 1:

1. First-Line Serum-Based Tests:

   • FIB-4 score (calculated using age, ALT, AST, and platelet count)

     • FIB-4 <1.3: Low risk of advanced fibrosis
     • FIB-4 >2.67: High risk of advanced fibrosis 1

   • NAFLD Fibrosis Score (NFS)

     • Uses age, BMI, hyperglycemia, platelet count, albumin, and AST/ALT ratio
     • Score <-1.455: Low risk of advanced fibrosis
     • Score >0.676: High risk of advanced fibrosis 1

2. Second-Line Tests (if available):

   • Enhanced Liver Fibrosis (ELF) test - measures three matrix turnover proteins 1
   • Proprietary tests like FibroTest/FibroSure, FIBROSpect NASH, or Hepamet Fibrosis Score 1

Imaging-Based Fibrosis Assessment

• Vibration Controlled Transient Elastography (VCTE/FibroScan)
  • Optimal cutoff for advanced fibrosis: 9.9 kilopascals 1
• Magnetic Resonance Elastography (MRE) - highly accurate but less available 1
• Shear Wave Elastography (SWE) 1

Metabolic Assessment

Since NAFLD is strongly associated with metabolic syndrome, assessment should include 1:

• Fasting glucose or HbA1c
• Lipid profile (triglycerides, HDL, LDL)
• Blood pressure measurement
• Waist circumference measurement

When to Consider Liver Biopsy

Liver biopsy remains the gold standard but should be reserved for specific situations 1:

• Patients with high risk of steatohepatitis and/or advanced fibrosis based on non-invasive tests
• When competing etiologies cannot be excluded
• Before starting pharmacological treatments
• For research purposes

Monitoring Recommendations

• For patients with low fibrosis risk: Repeat liver function tests and fibrosis assessment every 2-3 years
• For patients with indeterminate or high fibrosis risk: Referral to specialist for consideration of liver biopsy or more advanced testing

Common Pitfalls to Avoid

1. Normal liver enzymes don't exclude NAFLD - Up to 50% of patients with NAFLD have normal liver chemistries 2

2. AST:ALT ratio interpretation - While typically <1 in early NAFLD, this ratio may reverse as disease progresses 1

3. Relying solely on imaging - Ultrasound, CT, and MRI can detect steatosis but cannot reliably assess inflammation or fibrosis 1

4. Overlooking metabolic conditions - Always assess for diabetes, obesity, dyslipidemia, and hypertension 1

5. Inadequate alcohol history - Ensure accurate alcohol consumption history to differentiate NAFLD from alcoholic liver disease 1

By following this structured approach to laboratory testing and assessment, clinicians can effectively diagnose fatty liver disease, assess its severity, and monitor disease progression to improve patient outcomes.