Hepatic nodular ultrasound appearance in Wilson's disease: association with ultrasound-derived fat fraction but not fibrosis markers.

Background: Patients with Wilson's disease (WD) frequently exhibit nodular hepatic findings on ultrasonography. However, the clinical significance of these nodular features and their relationship with the severity of liver injury remain unclear. This study aimed to evaluate the association between sonographic nodular appearance in WD and noninvasive indicators of liver injury. Methods: This retrospective study consecutively enrolled patients diagnosed with WD between June 2024 and April 2025. All participants underwent standardized multimodal ultrasonographic evaluation, including conventional B-mode ultrasound to assess liver morphology, parenchymal echogenicity, and the presence of nodules, as well as portal vein diameter (PVD) and portal vein velocity (PVV). Shear wave elastography (SWE) and ultrasound-derived fat fraction (UDFF) measurements were also performed. Demographic data (age, sex, and body mass index), noninvasive fibrosis indices [aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 index (FIB-4)], liver function parameters (albumin, total bilirubin, and platelet count), and serum fibrosis markers (type IV collagen, hyaluronic acid, laminin, and procollagen III N-terminal peptide) were collected. Patients were categorized into nodular and non-nodular groups according to the presence of hepatic nodules on routine ultrasound. The nodular group was further stratified based on echogenicity into hyperechoic and hypoechoic subtypes. Multivariate logistic regression analysis was performed to identify independent factors associated with hepatic nodular appearance. Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal UDFF cutoff value for predicting hepatic nodularity. Results: A total of 175 patients with WD were included (107 males and 68 females). Of these, 37 patients (21%) were classified into the nodular group and 138 into the non-nodular group. Within the nodular group, 15 patients had hyperechoic nodules and 22 had hypoechoic nodules. No significant differences were observed between these subgroups in sex, age, body mass index, UDFF, liver stiffness measurement (LSM), or serum fibrosis markers (all P>0.05); therefore, they were combined for subsequent analyses. Multivariate logistic regression analysis demonstrated that, after adjustment for age, sex, body mass index, and other potential confounders, UDFF was the only independent factor associated with nodular ultrasound appearance [odds ratio: 1.254, 95% confidence interval (CI): 1.071-1.500, P=0.007]. The median UDFF was significantly higher in the nodular group than in the non-nodular group (6.0% Conclusions: The nodular ultrasound appearance in WD is more likely to reflect heterogeneous fatty infiltration secondary to uneven copper deposition rather than progression of hepatic fibrosis, with important implications for clinical evaluation and management.