肝豆状核变性临床诊断的难点与挑战

张宇; 杨永峰

doi:10.12449/JCH260303

肝豆状核变性临床诊断的难点与挑战

DOI: 10.12449/JCH260303

张宇,
杨永峰^, ,

南京市第二医院（南京中医药大学附属南京医院）感染/肝病科，南京 210003

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：张宇负责文献检索，资料分析，撰写及修改论文；杨永峰负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
杨永峰， yangyongfeng@njucm.edu.cn （ORCID： 0000-0002-3214-0038）

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出版历程
- 收稿日期: 2026-01-09
- 录用日期: 2026-02-09
- 出版日期: 2026-03-25

Dilemmas and challenges in the clinical diagnosis of Wilson disease

Yu ZHANG,
Yongfeng YANG^{,
,}

Department of Infectious Diseases and Hepatology，Nanjing Second Hospital （Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine），Nanjing 210003，China

More Information

Corresponding author: YANG Yongfeng， yangyongfeng@njucm.edu.cn （ORCID： 0000-0002-3214-0038）

摘要

摘要: 肝豆状核变性临床表型异质性强，常与胆汁淤积性肝病、活动性肝炎等肝病及神经精神疾病重叠，易致误诊、漏诊。本文聚焦临床易混淆环节，概述铜转运腺苷三磷酸酶β（ATP7B）基因功能缺陷的病理生理基础，系统阐述铜蓝蛋白、血清总铜/非铜蓝蛋白结合铜、24 h尿铜排泄量及D-青霉胺激发试验、肝铜定量与组织学检查在不同场景中的判读要点和局限，并总结相对可交换铜等新型动态铜指标在诊断、家系筛查与疗效监测中的潜力。同时讨论ATP7B基因检测在“灰区”病例中的价值、临床意义未明变异解读难点及我国人群突变谱特点，以及莱比锡评分在复杂肝病背景下可能出现的性能下降。总体而言，肝豆状核变性的诊断不宜依赖单一指标，应采用“表型-生化-动态铜指标-组织/基因-评分体系”的多维整合与分层决策路径，并结合我国真实世界数据优化关键阈值和流程，以提升早期识别与家系管理效率，改善患者长期预后。
- 肝豆状核变性 /
- 诊断 /
- 生物标记
Abstract: Wilson disease （WD） is characterized by marked heterogeneity in clinical phenotype， and it often overlaps with liver diseases （such as cholestatic liver diseases and active hepatitis） and neuropsychiatric diseases， which may easily lead to misdiagnosis or missed diagnosis. This article focuses on the confusing scenarios in clinical practice， reviews the pathophysiological basis of ATPase copper transporting beta （ATP7B） gene dysfunction， and systematically elaborates on the key interpretation points and limitations of ceruloplasmin， total serum copper/non-ceruloplasmin-bound copper， 24-hour urinary copper excretion， D-penicillamine challenge test， hepatic copper quantification， and histopathological assessment across different clinical scenarios. This article also summarizes the potential application of emerging dynamic copper indicators， such as relative exchangeable copper， in diagnosis， family screening， and treatment monitoring. In addition， it discusses the role of ATP7B genetic testing in “gray-zone” cases， difficulties in interpreting variants of uncertain significance， and the features of mutation spectrum in Chinese population， as well as the potential decline in diagnostic performance of the Leipzig scoring system in the context of complex liver diseases. Overall， the diagnosis of WD should not rely on a single indicator， and it is recommended to adopt a multidimensional hierarchical decision-making pathway that integrates phenotype， biochemical tests， dynamic copper indices， tissue/genetic evidence， and scoring systems. Furthermore， key thresholds and workflows should be optimized using real-world data from China， so as to enhance the efficiency of early identification and familial management， thereby improving the long-term prognosis of patients.
- Hepatolenticular Degeneration /
- Diagnosis /
- Biomarkers

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参考文献(54)

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