Non-invasive fibrosis tests in Wilson Disease: Insights from the international Wilson Disease Registry and Barcelona Cohort.

Introduction: Non-invasive tests (NITs) accurately detect fibrosis and may reduce the need for liver biopsy (LB). Detection of advanced fibrosis (≥F3) is clinically important for prognosis, but few studies have explored the use of NITs in patients with Wilson Disease (WD). Methods: In this multicentre observational study, adult and pediatric WD patients from seven international expert centers with histologic fibrosis staging were included. NITs (Transient elastography (TE), Fibrosis-4 index (FIB-4), AST to platelet-ratio (APRI), Steatosis-associated fibrosis estimator (SAFE), and NAFLD fibrosis score (NFS)) and clinical data were collected. NITs were compared with liver biopsy (LB) to detect advanced fibrosis (≥F3). Results: In total, 123 patients were included: median age was 30 years (IQR 17.4, 43.1); time from WD diagnosis to LB was 6.7 months (0.7, 144.1); 30.9% had advanced fibrosis (≥F3), while concomitant metabolic risk factors (obesity and diabetes) were rare. Overall, 64 patients had NITs measured within 1 year of the LB and constituted the primary analysis group. All NITs, except FIB-4, were significantly elevated in patients with ≥F3. TE had the best overall accuracy (AUC=0.79), and performed well at an optimized cut-off of ≥8.35 kPa (sens=0.88, spec=0.85). APRI had lower accuracy, but effectively ruled out ≥F3 at the optimized cut-off of ≥1.3 (AUC=0.71, sens=0.38, spec=1.00). Combining those into a score (APRITE) achieved an AUC of 0.88. Discussion: TE demonstrated good diagnostic performance for identifying advanced fibrosis in WD. APRI showed high specificity, while the exploratory APRITE score showed encouraging performance.