Phillips M J, Ackerley C A, Superina R A, Roberts E A, Filler R M, Levy G A
Department of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.
Lancet. 1996 Mar 30;347(9005):866-8. doi: 10.1016/s0140-6736(96)91347-1.
High hepatic copper concentrations have been reported in several liver disorders. We report six Native Canadian children with severe chronic cholestatic liver disease, who had excess hepatic copper and zinc.
The children, aged 22 months to 8 years, came from northern Ontario, Canada. All were referred for possible liver transplantation because of end-stage liver disease. We examined explanted liver samples (or liver biopsy material in one case) by scanning transmission electronmicroscopic (STEM) X-ray elemental microanalysis and atomic absorption spectrophotometry. Samples from four controls (two with no liver pathology, one with biliary atresia, and one with Wilson's disease) were also analysed by atomic absorption spectrophotometry.
The explanted livers showed similar distinctive signs of advanced biliary cirrhosis, and on electronmicroscopy there were dense deposits in enlarged lysosomes and in cytoplasm. Hepatic copper concentrations were many times higher in the five patients with measurements (47.6-56.9 microgram/g dry weight) than in two samples of normal control liver tissue (2.3 and 2.9 microgram/g). Similarly, hepatic zinc concentrations were many times higher in the patients than in controls (104-128 vs 1.9-3.2 microgram/g dry weight).
The excess copper may be due to chronic cholestasis but the excess zinc is unexplained. Since three of the patients are related (shared grandparents), a genetic disorder of metal metabolism is possible, but we cannot exclude environmental factors.
在几种肝脏疾病中都有肝脏铜浓度升高的报道。我们报告了6名患有严重慢性胆汁淤积性肝病的加拿大原住民儿童，他们的肝脏中铜和锌含量过高。
这些儿童年龄在22个月至8岁之间，来自加拿大安大略省北部。由于终末期肝病，他们均被转诊以评估是否可能进行肝移植。我们通过扫描透射电子显微镜（STEM）X射线元素微分析和原子吸收分光光度法检查了切除的肝脏样本（其中1例为肝活检材料）。还通过原子吸收分光光度法分析了4名对照者的样本（2名无肝脏病变，1名患有胆道闭锁，1名患有威尔逊病）。
切除的肝脏显示出晚期胆汁性肝硬化的相似特征性表现，电子显微镜检查发现溶酶体和细胞质中有致密沉积物。5例有测量数据的患者肝脏铜浓度（47.6 - 56.9微克/克干重）比两份正常对照肝组织样本（2.3和2.9微克/克）高很多倍。同样，患者肝脏锌浓度也比对照者高很多倍（104 - 128微克/克干重对1.9 - 3.2微克/克干重）。
铜过量可能是由于慢性胆汁淤积，但锌过量的原因不明。由于其中3名患者有亲属关系（拥有共同祖父母），金属代谢的遗传疾病是有可能的，但我们不能排除环境因素。
