Do you still need to check Fib-4 (Fibrosis-4) index in patients with a history of Primary Biliary Cholangitis (PBC)?

FIB-4 Testing in Patients with Primary Biliary Cholangitis

In patients with established Primary Biliary Cholangitis (PBC), FIB-4 testing is not recommended for fibrosis staging due to its suboptimal diagnostic performance. 1

Why FIB-4 Is Not Recommended in PBC

Serum-based fibrosis markers like FIB-4 have been specifically evaluated in PBC and found to be inadequate:

• A large study of 1,828 North American and European PBC patients showed FIB-4 had poor diagnostic performance with AUROCs of only 0.64 for significant fibrosis, 0.69 for advanced fibrosis, and 0.73 for cirrhosis—all below the acceptable threshold of 0.80 1

• Multiple retrospective studies from Western countries confirmed FIB-4's poor performance in PBC, with AUROCs ranging from just 0.35 to 0.70 for advanced fibrosis 1

• The European Association for the Study of the Liver (EASL) explicitly states that "serum markers of fibrosis and non-invasive scores (combination of clinical and laboratory variables) are not recommended for fibrosis staging in clinical practice" in PBC patients 1

Better Alternatives for Fibrosis Assessment in PBC

Instead of FIB-4, the following methods are recommended for fibrosis assessment in PBC:

1. Transient Elastography (FibroScan)

• First-line recommendation: VCTE (Vibration Controlled Transient Elastography) has superior diagnostic performance compared to serum markers in PBC 1
• When comparing diagnostic performance for advanced fibrosis, VCTE had an AUROC of 0.95 versus only 0.83 for FIB-4 1
• A cutoff value of 10 kPa is recommended to rule in advanced fibrosis/cirrhosis in PBC 1
• EASL strongly recommends VCTE as "the best surrogate marker for ruling in severe fibrosis/cACLD" in PBC patients 1

2. Point Shear Wave Elastography (pSWE)

• Shows promising results in PBC with AUROCs of 0.81 for significant fibrosis and 0.91 for advanced fibrosis 1

Clinical Implications and Monitoring Approach

For patients with established PBC:

1. Initial assessment: Use VCTE (FibroScan) as the primary non-invasive tool for fibrosis staging
2. Regular monitoring: Continue with VCTE for fibrosis assessment during follow-up
3. Laboratory monitoring: Annual liver function tests (total bilirubin, AST, ALT, alkaline phosphatase, GGT, platelet count) during clinical stability remain important for disease activity monitoring, not for fibrosis staging 1

Common Pitfalls to Avoid

• Don't rely on FIB-4, APRI, or other serum markers for fibrosis staging in PBC patients as they have been proven inadequate in this specific disease 1
• Don't assume all non-invasive tests perform equally across different liver diseases; PBC has unique pathophysiology requiring specific validated approaches
• Don't miss the opportunity for elastography assessment, which is significantly more accurate than serum-based markers in PBC 1

Special Considerations

Even in patients with biochemical treatment response to ursodeoxycholic acid (UDCA), fibrosis stage remains an independent predictor of outcome in PBC 2. Therefore, accurate fibrosis assessment using appropriate methods (elastography rather than serum markers) is crucial for proper risk stratification and management decisions.