Non-invasive fibrosis tests in Wilson Disease: Insights from the international Wilson Disease Registry and Barcelona Cohort.
Frederik Teicher Lauridsen Kirk, Zoe Mariño, Uyen Kim To, Asim Ulcay, Hatice Maras, Sefa Keserci, Kaitlin Maciejewski, Isabelle Mohr, Regino P. González-Peralta, Sanjiv Harpavat, Sabela Lens, María-Carlota Londoño, Sihoun Hahn, Thomas Damgaard Sandahl, Yanhong Deng, Alba Diaz, Michael L. SchilskyIntroduction:
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.