Brewer G J, Yuzbasiyan-Gurkan V, Lee D Y, Appelman H
Department of Human Genetics, University of Michigan, Ann Arbor 48109-0618.
J Lab Clin Med. 1989 Dec;114(6):633-8.
Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.
11例新诊断的威尔逊病患者接受醋酸锌治疗，作为唯一的抗铜疗法。治疗时间为8至37个月。其中3例患者有症状；8例无症状患者因有症状的患病同胞而确诊。所有患者临床情况良好。口服铜64吸收受阻，提示铜吸收受到抑制。24小时尿铜和非铜蓝蛋白血浆铜（游离铜）值降低。治疗前肝源性血清酶升高的患者，其值也普遍降低。最初进行了经皮肝活检，7例患者在锌治疗12至35个月后重复活检。其中5例患者的第二次活检标本显示铜含量高于第一次。在这5例中的3例中，第二次活检6至23个月后的第三次活检显示肝铜值已恢复至基线值或更低。1例患者的初始活检标本显示有活动性炎症，治疗后炎症消退。所有活检均显示典型的肝硬化组织学瘢痕，且在治疗过程中似乎没有变化。我们得出结论，在锌治疗早期肝铜可能会暂时增加，但积累的铜以无毒形式被隔离。基于动物研究，我们推测这种隔离的铜主要与锌诱导的高水平肝金属硫蛋白结合。锌似乎是威尔逊病患者初始治疗的合理选择，尤其是那些无症状疾病患者。
