Kazemi Kourosh, Geramizadeh Bita, Nikeghbalian Saman, Salahi Heshmatollah, Bahador Ali, Reza Nejatollahi Seyed Mohammad, Dehghani Seyed Mohsen, Dehghani Masood, Kakaei Farzad, Malek-Hosseini Seyed Ali
Shiraz Organ Transplantation Center, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
Exp Clin Transplant. 2008 Dec;6(4):261-3.
Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients.
Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist.
Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05).
D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.
威尔逊病是一种以铜代谢紊乱、铜过载为特征的疾病。ATP7B基因突变导致ATP7B蛋白功能障碍，肝细胞向胆汁中排泄铜减少。过量的铜积累会导致肝损伤。D-青霉胺主要可抑制纤维生成，防止肝脏出现瘢痕病变。我们在患者中研究了这一现象。
对2000年至2008年间诊断为患有威尔逊病且有肝神经症状并接受肝移植的26例患者的移植肝病理切片进行回顾性研究。根据移植前使用D-青霉胺的病史将患者分为两组。纤维化和炎症程度分为轻度（1级）、中度（2级）和重度（3级），由一位公正的肝病病理学家进行评估。
26例威尔逊病患者（20例男性，6例女性），平均年龄17.6±8.6岁，69%（18/26）在肝移植前有6个月至9年（平均3.4±2.7年）的D-青霉胺使用史。在D-青霉胺组，14例患者（77%）为1级纤维化。2级和3级纤维化分别见于5.6%和16%的患者。在D-青霉胺组，44%（8/18）的患者炎症为3级，44%（8/18）为2级，11%（2/18）为1级。在非D-青霉胺组（8例患者）中，纤维化程度为3级（62%）、2级（25%）和1级（12%）；87%的患者有2级和3级炎症。D-青霉胺组的纤维化程度显著低于非D-青霉胺组（P<0.05）。
D-青霉胺可能降低威尔逊病患者的肝纤维生成率。
