When should I order FibroSure versus Fib-4 for suspected liver disease?

When to Order FIB-4 vs. FibroSure Tests in Outpatient GI Practice

FIB-4 should be used as the first-line non-invasive test for liver fibrosis assessment in all patients with suspected NAFLD, while FibroSure (proprietary test) should be reserved for second-tier testing in patients with indeterminate FIB-4 results. 1

Initial Risk Assessment with FIB-4

When to Order FIB-4:

• As first-line screening in all patients with:
  • Suspected NAFLD (especially with metabolic risk factors)
  • Type 2 diabetes
  • Obesity
  • Metabolic syndrome
  • Persistently elevated liver enzymes

Advantages of FIB-4:

• Simple calculation using readily available parameters:
  • Age
  • AST and ALT levels
  • Platelet count
• No additional cost beyond routine labs
• High negative predictive value (≥90%) for excluding advanced fibrosis 1
• Correlates well with clinical outcomes in NAFLD patients 1

FIB-4 Interpretation:

• Low risk: <1.3 (<2.0 in patients >65 years old)
  • Advanced fibrosis unlikely
  • Repeat testing in 2-3 years 1
• Indeterminate: 1.3-2.67
  • Requires second-tier testing
• High risk: >2.67
  • High probability of advanced fibrosis (60-80% PPV)
  • Refer to hepatology for further evaluation 1

Second-Tier Assessment with FibroSure

When to Order FibroSure:

• For patients with indeterminate FIB-4 results (1.3-2.67)
• When elastography (VCTE/FibroScan) is unavailable
• When discordant results exist between other non-invasive tests
• In specialized GI/hepatology settings for more precise fibrosis staging

Advantages of FibroSure:

• Proprietary blood test with good diagnostic performance
• May provide more detailed assessment than FIB-4
• Can be used as part of a sequential testing strategy 1, 2

Limitations of FibroSure:

• Higher cost than FIB-4
• Not recommended as first-line test due to cost considerations 1, 2
• Cannot reliably distinguish between different levels of fibrosis 2
• Several factors unrelated to fibrosis can contribute to false-positive results 2

Evidence-Based Testing Algorithm

1. Initial Assessment: Calculate FIB-4 for all patients with suspected NAFLD or risk factors

2. If FIB-4 < 1.3 (or <2.0 in patients >65 years):

   • Low risk of advanced fibrosis
   • Routine follow-up
   • Repeat FIB-4 in 2-3 years 1

3. If FIB-4 > 2.67:

   • High risk of advanced fibrosis
   • Direct referral to hepatology
   • Consider liver stiffness measurement or biopsy 1

4. If FIB-4 is indeterminate (1.3-2.67):

   • Order second-tier test:
     • FibroSure if elastography unavailable
     • Alternatively, consider VCTE/FibroScan if available (preferred) 1

Cost-Effectiveness Considerations

A two-tier approach using FIB-4 followed by a second test for indeterminate results has been shown to be more cost-effective than using either test alone 3. This approach:

• Reduces unnecessary referrals by up to 85%
• Increases detection of advanced fibrosis by >100%
• Significantly reduces cost per case of advanced fibrosis detected 3

Important Caveats

• FIB-4 has lower sensitivity in patients with diabetes and may produce more false negatives in this population 4
• Both tests have limitations in detecting intermediate stages of fibrosis (F2)
• Age significantly affects FIB-4 results, requiring adjusted cutoffs for older patients
• Neither test can replace liver biopsy for definitive diagnosis of NASH or precise fibrosis staging
• Sequential testing (FIB-4 followed by FibroSure or elastography) provides better diagnostic accuracy than either test alone 1, 5

This structured approach allows for efficient risk stratification, reduces unnecessary referrals, and ensures appropriate identification of patients with advanced liver disease who require specialist care.