What is the role of Fibrotest (fibrosis test) in assessing and managing liver fibrosis?

Role of FibroTest in Assessing and Managing Liver Fibrosis

FibroTest is an effective non-invasive biomarker for assessing liver fibrosis across various chronic liver diseases, demonstrating comparable accuracy to liver biopsy with an area under the ROC curve (AUROC) of 0.84 for diagnosing significant fibrosis. 1

Overview of FibroTest

• FibroTest (also known as FibroSure in the US) is a patented serum biomarker panel that includes five components: alpha-2-macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl transferase (GGT), and bilirubin 2
• Unlike indirect markers such as APRI and FIB-4, FibroTest incorporates substances directly related to extracellular matrix turnover and liver fibrosis, providing better diagnostic performance for significant fibrosis and cirrhosis 2
• FibroTest results range from 0 to 1, with higher values indicating more advanced fibrosis 2

Diagnostic Performance

Chronic Hepatitis C (CHC)

• FibroTest was initially developed in a cohort of 339 patients with CHC, demonstrating an AUROC of 0.87 for diagnosing significant fibrosis with a cutoff value of 0.48 (sensitivity 75%, specificity 85%) 2
• In meta-analyses, FibroTest showed:
  • At low cutoff values (0.1-0.3): sensitivity 91%, specificity 41% for significant fibrosis 2
  • At high cutoff values (0.6-0.7): sensitivity 57%, specificity 85% for significant fibrosis 2
  • AUROCs of 0.72-0.83 for significant fibrosis and 0.81-0.92 for cirrhosis 2

Chronic Hepatitis B (CHB)

• In a Korean study of 194 patients with CHB, FibroTest demonstrated:
  • AUROC of 0.90, sensitivity 79%, specificity 93% for significant fibrosis 2
  • AUROC of 0.87, sensitivity 80%, specificity 84% for cirrhosis 2
• A meta-analysis of 16 studies including 2,494 CHB patients found sensitivity of 61% and specificity of 79% for diagnosing significant fibrosis 2

Other Chronic Liver Diseases

• FibroTest has been validated in alcoholic liver disease (ALD) with an AUROC of 0.86-0.87 2, 1
• In non-alcoholic fatty liver disease (NAFLD), FibroTest shows an AUROC of 0.84 1
• Overall diagnostic performance is consistent across different etiologies of chronic liver disease 1, 3

Comparative Performance with Other Non-Invasive Tests

• FibroTest outperformed FIB-4 and APRI in diagnosing significant fibrosis and cirrhosis in patients with chronic hepatitis C 2
• When compared to the Enhanced Liver Fibrosis (ELF) test in a direct comparison study, both tests showed comparable diagnostic accuracy (AUROC for cirrhosis: FibroTest 0.91 vs. ELF 0.92) 4
• Compared to Vibration-Controlled Transient Elastography (VCTE/FibroScan), serum tests like FibroTest can be performed in a higher proportion of patients without technical limitations related to obesity or ascites 4

Clinical Applications

• FibroTest is valuable for:
  • Initial assessment of fibrosis stage in patients with chronic liver disease 2
  • Determining need for antiviral therapy in viral hepatitis (treatment typically indicated for ≥F2 fibrosis) 2
  • Monitoring disease progression and prognosis 1
  • Reducing need for liver biopsy, particularly in patients with contraindications 2

Limitations and Considerations

• FibroTest has several important limitations:
  • False-negative results can occur due to acute inflammation (which increases haptoglobin) 2
  • False-positive results may occur with hemolysis (which decreases haptoglobin) 2
  • The test requires multiple indicators, making it more time-consuming and costly than simple serum markers like APRI or FIB-4 2
  • Like other serum markers, FibroTest has better diagnostic performance for cirrhosis than for significant fibrosis 2
  • Cutoff values vary between studies, requiring careful interpretation 2

Implementation in Clinical Practice

• FibroTest can be used in a stepwise approach:
  • Initial screening with simple serum markers (APRI, FIB-4) due to their lower cost and wider availability 2
  • FibroTest as a second-line test for indeterminate cases or to confirm results 2
  • Combined with elastography methods for improved diagnostic accuracy 5
• FibroTest has prognostic value comparable to or better than liver biopsy in predicting liver-related complications or mortality 1

Future Directions

• Further validation with large cohorts of patients from different populations is needed 2
• More research is required to assess the utility of FibroTest for monitoring fibrosis changes after treatment, particularly after sustained virologic response in patients with chronic hepatitis C 2
• Emerging techniques including lipidomic, proteomic, and microRNA signatures may complement or enhance current non-invasive fibrosis assessment methods 5