Non-invasive assessment of hepatic steatosis in Wilson Disease: An international registry-based study - 29/10/26

Doi : 10.1016/j.clinre.2026.102933

Frederik Teicher Lauridsen Kirk ^a,^b,^⁎ , Asim Ulcay ^c, Hatice Maras ^c, Sefa Keserci ^c, Alba Diaz ^d, Kaitlin Maciejewski ^e, Regino González-Peralta ^f,^†, Rima Fawaz ^c, Sanjiv Harpavat ^g, Uyen Kim To ^c, Sabela Lens ^h,ⁱ, María-Carlota Londoño ^h,ⁱ, Yanhong Deng ^e, Thomas Damgaard Sandahl ^a,^b,ⁱ, Michael L. Schilsky ^c, Zoe Mariño ^h,^i,^⁎

^a Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark

^b Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

^c Departments of Medicine and Surgery, Yale University Medical Center, New Haven (CT), US

^d Pathology Department, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Universitat de Barcelona, Spain

^e Yale Center for Analytical Sciences, Yale University, New Haven (CT), US

^f Advanced Hepatology and Liver Transplant, AdventHealth for Children, AdventHealth Transplant Institute, Orlando (FL), US

^g Department of Pediatrics, Texas Children’s Hospital and Baylor College of Medicine, Houston (TX), US

^h Liver Unit, Hospital Clínic Barcelona, IDIBAPS, CIBERehd, Universitat de Barcelona, Barcelona, Spain

ⁱ ERN-RARE Liver, Hamburg, Germany

^⁎ Corresponding authors at: Palle Juul-Jensens Blvd. 99, 8200, Aarhus N, Denmark or C/Villarroel 170, CP 08036, Barcelona, Spain. Palle Juul-Jensens Blvd. 99, 8200, Aarhus N, Denmark or C/Villarroel 170, CP 08036 Barcelona Spain

Highlights

•	Moderate-to-severe steatosis is common in Wilson Disease.
•	Cap is a promising NIT for steatosis in Wilson Disease.
•	CAP correlates strongly with histological steatosis grade in Wilson Disease.
•	A Wilson Disease specific CAP cut-off of ≥291 dB/m was identified.
•	HSI showed poor accuracy in Wilson Disease.

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Abstract

Background

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.

Methods

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.

Results

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)).

Conclusions

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.

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Keywords : Copper, Transient elastography, Fatty liver, Hepatolenticular degeneration, Diagnostic accuracy, Rare liver disease, Steatotic liver disease