1H NMR-based metabolomic study of striatal injury in rats with copper-loaded Wilson's disease by Chinese and Western medicine intervention.

OBJECTIVE: To investigate the metabolic mechanisms of Chinese and Western medicines on the metabolic network of striatal injury in a copper-loaded rat model of Wilson disease (WD) from a metabolomic perspective. METHODS: We divided 60 rats into 4 groups of 15 rats each according to a random number table, namely the control group, the model group, the Bushen Huoxue Huazhuo Recipe group, and the penicillamine group, and subsequently replicated the WD copper-loaded rat model according to the literature method for a total of 12 weeks. From the 7th week onwards, each intervention group was given an equivalent dose of the corresponding drug, and the control and model groups were given an equal volume of saline gavage until the end of the model replication. We used 1H NMR metabolomics techniques combined with multivariate statistical methods to describe the changes in the striatal metabolic profile of nerve injury in Wilson's disease and to analyze the effect of different treatments on their biomarker interventions. RESULTS: Nerve cell damage was evident in the WD copper-loaded rat model and could be reduced to varying degrees by different methods of intervention in the striatal nerve cells. The content of glycine, serine metabolism, and valine metabolism decreased in WD copper-loaded rat model; aspartate content increased after penicillamine intervention; glycolytic metabolism, valine metabolism, taurine metabolism, and tyrosine metabolism increased in the group of Bushen Huoxue Huazhuo Recipe. CONCLUSION: Different intervention methods of Chinese and Western medicine affect aspartate, glycolysis, taurine, tyrosine, valine, and carbon metabolism in striatal tissues of WD copper-loaded rats, and can regulate the metabolism of small molecules, which in turn have certain repairing effects on nerve damage in WD copper-loaded rats.

Application of attenuation coefficient in the assessment of hepatic involvement in children and adolescents with Wilson's disease.

BACKGROUND: To investigate whether the attenuation coefficient (ATT) can be used as a noninvasive index to assess liver involvement in children and adolescents with Wilson's disease (WD). METHODS: Children and adolescents diagnosed with WD were retrospectively collected from the First Affiliated Hospital of the Anhui University of Traditional Chinese Medicine between May 2022 and August 2022. The findings on ATT, Shear Wave Measurement (SWM), AST to platelet ratio index (APRI), and fibrosis 4 (FIB-4) score were obtained. The liver involvement of WD was classified into 3 groups based on serum levels of collagen type IV (CIV), hyaluronic acid (HA), laminin (LN) and precollagen type III N-terminal peptide (PIIINP): (1) Group1 (n = 25), no abnormalities in CIV, HA, LN and PIIINP; (2) Group2 (n = 19), elevation of 1 or 2 indexes in CIV, HA, LN, and PIIINP; Group3 (n = 18), elevation of 3 or 4 indicators in CIV, HA, LN, and PIIINP. The levels of ATT, SWM, APRI and FIB-4 were compared between the 3 groups; and correlation of ATT with SWM and triglyceride (TG) was performed using Spearman's correlation analysis. The Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of ATT alone and its combination with SWM, APRI, and FIB-4 in children and adolescents with WD. RESULTS: A total of 62 children and adolescents with WD were retrospectively retrieved. ATT levels were significantly different in intergroup comparisons (P < 0.001). The ROC curve showed that the area under the curve (AUC) for the diagnosis of hepatic steatosis using ATT was 0.714, 0.712 and 0.867 in Group 1 versus Group 2, Group 2 versus Group 3, and Group 1 versus Group 3, respectively; the sensitivity for the diagnosis of hepatic steatosis in Group 1 versus Group 2 was 89.47% with the cutoff value of ATT of 0.73 dB/cm/MHz. No significant correlation found between ATT and TG (ρ = 0.154, P = 0.231). Compared to ATT alone, the combination of ATT with APRI and FIB-4 or the combination of ATT with SWM, APRI, and FIB-4 showed a better diagnostic efficacy in Group 1 versus Group 2 (both P = 0.038). CONCLUSION: ATT could be used as a non-invasive index for the evaluation of liver steatosis in children and adolescents with WD, with a good clinical applicative value. Furthermore, ATT in combination with APRI, FIB-4, and SWM might have better diagnostic efficacy than ATT alone.

Liver stiffness assessed by real-time two-dimensional shear wave elastography predicts hypersplenism in patients with Wilson's disease: a prospective study.

BACKGROUND: The current study aimed to explore the value of liver stiffness assessed by two-dimensional real-time shear wave elastography (2D-SWE) to predict hypersplenism occurrence in Wilson's disease (WD) patients. METHODS: Ninety WD patients were enrolled in this prospective study between May 2018 and December 2018. Baseline clinical data and ultrasound imaging including 2D-SWE liver stiffness of WD patients were collected. After enrollment, patients had follow-ups for 24 months or until they developed hypersplenism. The hypersplenism risk factors were determined using Cox regressions and receiver operating characteristic curves (ROC). RESULTS: Twenty-nine (32.2%) patients developed hypersplenism. Age, portal vein diameter, and liver stiffness were independent hypersplenism risk factors in WD patients. The cutoff value of liver stiffness to predict hypersplenism was 10.45 kPa, with sensitivity and specificity of 75.9% and 73.8%, respectively. Patients were divided into two groups according to liver stiffness: ≥ 10.45 kPa (57.9% with hypersplenism) or < 10.45 kPa (13.5% with hypersplenism). The median time between enrollment and hypersplenism development was 15 months vs. 22 months (p < 0.001) for the two groups, respectively. CONCLUSION: The measurement of liver stiffness by 2D-SWE can be a reliable hypersplenism predictor in WD patients. Therefore, dynamic monitoring of WD patients using 2D-SWE is crucial for the early diagnosis of hypersplenism.