A Novel Fibroblast Activation Protein-Based Algorithm to Assess Fibrosis in Metabolic Dysfunction-Associated...

Area of Science:

• Hepatology
• Biomarker Discovery
• Diagnostic Algorithms

Background:

• Accurate noninvasive fibrosis testing is essential for managing metabolic dysfunction-associated steatotic liver disease (MASLD).
• Circulating fibroblast activation protein (cFAP), a marker of activated fibrogenic cells, was evaluated for its diagnostic potential.
• A novel algorithm, the FAP Index, was developed to assess liver fibrosis in MASLD patients.

Purpose of the Study:

• To evaluate the diagnostic accuracy of the FAP Index for detecting advanced liver fibrosis (F3-F4) in MASLD.
• To assess the utility of the FAP Index in reducing indeterminate results when combined with existing noninvasive tests like FIB-4 and NAFLD Fibrosis Score (NFS).

Main Methods:

• Two retrospective cohorts (n=160 training, n=332 validation) from tertiary hepatology clinics were analyzed.
• The FAP Index was developed using logistic regression, incorporating age, type 2 diabetes, alanine transaminase, and ordinal cFAP levels.
• cFAP was measured using a rapid, single-step enzyme assay.

Main Results:

• The FAP Index demonstrated strong diagnostic accuracy for advanced fibrosis, with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.875 in the training cohort and 0.841 in the validation cohort.
• Specific cutoffs for the FAP Index effectively excluded (low cutoff: 0.157) or predicted (high cutoff: 0.695) advanced fibrosis.
• Combining FAP Index with FIB-4 reduced indeterminate results by over one-third, and with NFS by approximately 70%.

Conclusions:

• The FAP Index offers a rapid, robust, and noninvasive method for liver fibrosis risk stratification in MASLD patients.
• Its application following FIB-4 or NFS significantly decreases indeterminate results without compromising negative predictive value, enhancing diagnostic efficiency.
• The FAP Index is a valuable tool for primary care, aiding in efficient liver fibrosis triage without requiring elastography.