Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University Vienna, Austria.
Department of General Internal Medicine, Bern University Hospital, Bern, Switzerland.
Clin Gastroenterol Hepatol. 2014 Apr;12(4):683-9. doi: 10.1016/j.cgh.2013.09.025. Epub 2013 Sep 25.
BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease.
We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry.
The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008).
Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.
威尔逊病是一种常染色体隐性遗传病，影响铜代谢，导致铜在肝脏、中枢神经系统和肾脏中蓄积。目前关于大型队列的长期结果和生存率的数据很少，我们对奥地利一个经充分特征描述的威尔逊病患者队列进行了这些特征的研究。
我们分析了 1961 年至 2013 年间诊断为威尔逊病的 229 例患者的数据；其中 175 例定期就诊于威尔逊病门诊诊所，或其医生联系以获取有关疾病和治疗状况以及结局的信息。对于在随访期间失联的 53 例患者，通过奥地利死亡登记处查明了已死亡患者及其死因。
中位观察期为 14.8±11.4 年（范围，0.5-52.0 年），累计患者-年 3116 例。其中，61%的患者以肝脏疾病起病，27%以神经系统症状起病，10%为无症状期经家系筛查诊断。以肝脏疾病起病的患者诊断年龄较轻（21.2±12.0 岁），低于以神经系统疾病起病的患者（28.8±12.0 岁；P<.001）。2%的患者不确定症状的确切出现或起始时间。大多数患者经螯合治疗稳定（35%）或改善（26%完全缓解，24%改善），但 15%恶化；8%需要进行肝移植，7.4%在观察期间死亡（71%的死亡与威尔逊病相关）。调整年龄和性别后，威尔逊病患者的 20 年生存率（92%）低于健康奥地利人（97%）（P=.03）。诊断时的肝硬化是死亡（比值比，6.8；95%置信区间，1.5-31.03；P=.013）和需要肝移植（比值比，07；95%置信区间，0.016-0.307；P<.001）的最佳预测因子。诊断后 20 年，仅有 84%的肝硬化患者存活（与健康奥地利人相比，P=.008）。
总体而言，接受充分威尔逊病治疗的患者具有良好的长期预后。然而，肝硬化增加了死亡和肝病的风险。早期诊断，在肝硬化前期，可能会延长生存时间并减少肝移植的需要。
