Orphanet Journal of Rare Diseases | European survey of Wilson disease management reveals treatment consistency and key differences

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The study, through a physician-based questionnaire across Europe, reveals the consistency and variations in the management of Wilson disease across different medical centers, emphasizing the diversity in treatment approaches, dietary recommendations, and patient follow-up, and highlighting the need for more high-quality research to guide clinical practice.

 

Literature Summary
The article, titled 'Management of Wilson disease across Europe: an international physician-oriented survey by the ERN-RARE Liver group', published in the Orphanet Journal of Rare Diseases, reviews and summarizes the management practices of Wilson Disease (WD) across Europe. Using survey data from 62 physicians across 20 countries, the study analyzed consistency and differences in WD diagnosis, treatment, monitoring, and collaboration with patient organizations. The article points out that while most centers follow international guidelines, there are still significant variations in the initial treatment of non-hepatic WD, availability of trientine dihydrochloride (TRI), and recommendations for low-copper diets. Furthermore, it emphasizes the importance of collaboration with patient organizations, particularly in improving quality of life and treatment adherence. The entire paragraph is coherent and logically structured, ending with a Chinese period.

Background
Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism that leads to copper accumulation in the liver and brain, which can be fatal if untreated. Current treatments include copper chelators (e.g., D-penicillamine and trientine dihydrochloride) and zinc salts, which manage copper load by increasing urinary excretion or reducing intestinal absorption. Although international guidelines such as AASLD and EASL exist, significant differences persist in clinical practice across centers, particularly in diagnostic tools, treatment selection, monitoring frequency, and dietary recommendations. Especially for non-hepatic WD patients, treatment strategies remain controversial, and some centers cannot provide complete treatment options due to cost or drug availability. In addition, the long-term efficacy of low-copper diets remains debated, with some studies suggesting negative impacts on quality of life and lacking clear clinical support. This study aims to assess the consistency and differences in WD management across European centers to provide evidence for future multicenter clinical research. Ends with a period.

 

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Study Methods and Experiments
The study employed a 37-question online questionnaire distributed across Europe by the ERN-RARE Liver group, covering aspects of WD diagnosis, treatment, monitoring, and collaboration with patient organizations. Centers were categorized as small (<30 patients/year) or large (≥30 patients/year) based on annual patient volume. Data were analyzed using STATA 18.0 and GraphPad Prism 10.0 to assess variations in treatment protocols, monitoring parameters, dietary advice, and collaboration models.

Key Findings and Perspectives

• Most European WD centers follow international guidelines such as EASL, AASLD, or ESPGHAN, but some smaller centers face limitations in the availability of trientine (TRI), and others cannot offer TRI due to cost issues.
• Although most centers have standard diagnostic tools (e.g., slit-lamp examination, serum ceruloplasmin testing, genetic sequencing), larger centers are more likely to offer research-oriented diagnostics such as CuEXC and 64Cu scintigraphy.
• There is significant variation in the initial treatment strategies for non-hepatic WD patients, with neurologists favoring monotherapy with chelators, while some centers prefer monotherapy with zinc or combination therapy, reflecting the lack of strong supporting evidence.
• Recommendations for low-copper diets vary widely across centers; some recommend short-term use, others long-term, and the 2025 EASL guidelines for the first time recommend short-term low-copper diets.
• Collaboration with patient organizations varies significantly across countries; 38% of centers report limited contact, and 31% operate in countries without relevant patient organizations, underscoring the importance of strengthening patient support networks.
• While most centers use 24-hour urinary copper excretion for monitoring, some differ in whether to pause treatment, which may affect the assessment of bioavailable copper.

Implications and Future Directions
This study provides a systematic evaluation of the consistency and differences in WD management across Europe, highlighting the need for standardization in treatment strategies, dietary recommendations, and collaboration with patient organizations. Future research should focus on treatment strategies for non-hepatic WD, clinical validation of CuEXC and 24H-UCE, and the role of patient organizations in treatment adherence. Moreover, with the advancement of international clinical trials, this survey data can serve as a critical reference for standardizing WD management.

 

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Conclusion
In summary, this study reveals a high level of consistency among European WD centers in management practices, particularly in adherence to international guidelines and the use of Leipzig criteria for diagnosis. However, significant variations still exist in the initial treatment of non-hepatic WD, availability of trientine (TRI), low-copper dietary recommendations, collaboration with patient organizations, and monitoring approaches. These differences may stem from a lack of robust clinical evidence and reflect the diversity in management strategies across different healthcare systems. The findings provide valuable insights for future multicenter collaborations and international clinical trial designs, emphasizing the need for standardized management tools, enhanced patient support networks, and validated monitoring parameters. Additionally, with the 2025 EASL guideline update, some practices (e.g., zinc use in neurological WD) may gain stronger support, though further research is still required to optimize treatment strategies and improve patient adherence.

 

Frederik Teicher Kirk, Karina Stubkjær Rewitz, Zoe Mariño, Piotr Socha, and Thomas Damgaard Sandahl. Management of Wilson disease across Europe: an international physician-oriented survey by the ERN-RARE Liver group. Orphanet Journal of Rare Diseases.