Hepatic steatosis is an early histological feature of Wilson Disease (WD) with unknown clinical significance. Non-invasive tests (NITs) for steatosis are increasingly used, despite a lack of data supporting their utility in WD.

International registry study including adults and children with WD, histological hepatic steatosis grading, and available NITs [hepatic steatosis index (HSI) or controlled attenuation parameter (CAP)]. NITs were tested against liver biopsy (LB) to detect moderate-to-severe steatosis (MSSt), and WD-specific cut-offs were developed. The analysis focused on patients with ≤1 year between NITs and LB.

103 patients with WD and histological steatosis grading were included, with 57 evaluated at diagnosis. Overall, MSSt was present in 35.9%. NITs were measured ≤1 year from LB in 59 (57.3%); Among those, CAP, but not HSI, was significantly elevated in MSSt and increased with histologic steatosis grade (p=0.0017). Similarly, CAP showed excellent accuracy for detecting MSSt in WD (AUROC=0.93 (0.83, 1.00) vs only 0.64 (0.44, 0.84) for HSI). An optimized CAP cut-off of ≥291 dB/m resulted in a sensitivity of 0.78 (0.40, 0.97) and specificity of 1.00 (0.81, 1.00). Additionally, an exploratory combined score of CAP & ALT further improved MSSt detection (AUROC=0.96 (0.88, 1.00)).

MSSt is common in WD, and CAP showed promising diagnostic performance for detecting MSSt in WD at diagnosis and at follow-up. Future studies are needed to determine the potential clinical and prognostic significance of MSSt in WD. This study also highlights the need for assessing NITs and their cut-offs in rare hepatic storage disorders.