Stremmel Wolfgang, Longerich Thomas, Liere René, Vacata Vladimir, van Helden Josef, Weiskirchen Ralf
Pracice for Gastroenterology, Medical Center Baden-Baden, Baden-Baden D-76530, Germany.
Department of General Pathology, University Heidelberg Hospital, Institute of Pathology, University of Heidelberg, Heidelberg D-69115, Germany.
World J Clin Cases. 2021 Feb 26;9(6):1386-1393. doi: 10.12998/wjcc.v9.i6.1386.
In Wilson disease lack of biliary copper excretion causes hepatocellular injury by accumulation of free toxic copper. Its overspill to serum accounts for neuronal damage as second common manifestation. Therapy with copper chelators or zinc targets the removal of this free copper. However, in some patients liver disease persists for unknown reason despite normalized free copper. The discovery of a hyperimmunity as a contributing pathogenetic factor was discovered in this case report with implication also for other liver diseases.
A 9-year-old girl was diagnosed in August 2009 by family screening of having asymptomatic Wilson disease with elevated transaminases. Already at time of diagnosis antinuclear antibodies (ANA) were elevated without hyperimmunoglobulinemia (immunoglobulin G, IgG). After one year of therapy with D-penicillamine transaminases normalized together with free serum copper. Under continuous therapy with copper chelators free copper remained normal until today, whereas transaminases raised to alanine aminotransferase values of 571 U/L in December 2019. For hyperimmunity a tentative steroid course on top of D-penicillamine improved transaminases. Thus hyperimmunity may have impact on liver inflammation after control of the metabolic disturbance. A retrospective cohort study confirmed the common association of elevated transaminases with ANA, but no IgG elevation.
This hyperimmune-triggered condition may represent a new entity which per se or on top of other liver diseases induces liver inflammation responsive to steroids.
在威尔逊病中，胆汁铜排泄缺乏导致游离毒性铜积累，从而引起肝细胞损伤。其溢出到血清中是导致神经元损伤的第二常见表现。用铜螯合剂或锌进行治疗的目标是清除这种游离铜。然而，在一些患者中，尽管游离铜水平恢复正常，但肝病仍持续存在，原因不明。在本病例报告中发现超敏反应是一个致病因素，这对其他肝病也有启示意义。
一名9岁女孩于2009年8月通过家族筛查被诊断为无症状威尔逊病，转氨酶升高。在诊断时抗核抗体（ANA）就已升高，但无高免疫球蛋白血症（免疫球蛋白G，IgG）。用青霉胺治疗一年后，转氨酶与游离血清铜一起恢复正常。在持续使用铜螯合剂治疗的情况下，游离铜至今仍保持正常，而在2019年12月转氨酶升至丙氨酸转氨酶值571 U/L。对于超敏反应，在青霉胺基础上进行了一个试验性的类固醇疗程，转氨酶有所改善。因此，在代谢紊乱得到控制后，超敏反应可能会对肝脏炎症产生影响。一项回顾性队列研究证实了转氨酶升高与ANA之间的常见关联，但无IgG升高。
这种超敏反应引发的病症可能代表一种新的实体，其本身或在其他肝病基础上可诱发对类固醇有反应的肝脏炎症。
