29例肝豆状核变性临床病理特点分析  

Clinicopathological features of Wilson disease： report of 29 cases

作　　者：张玉果[1] 南月敏[1] 赵素贤[1] 王泰龄[2] 姜君[3] 

机构地区：[1]河北医科大学第三医院中西医结合肝病科,石家庄050051 [2]中日友好医院病理科 [3]中国科学院北京基因组研究所基因组科学与信息重点实验室

出　　处：《中华医学杂志》2013年第18期1422-1425,共4页National Medical Journal of China

摘　　要：目的对29例肝豆状核变性（Wilson病，WD）患者的临床病理特点归纳总结。方法回顾性分析2007年1月至2012年10月河北医科大学第三医院和北京中日友好医院29例WD患者的临床资料，分析指标包括临床表现、肝脏生化指标、血清铜蓝蛋白、24h尿铜、ATP7B基因检测及病理学检查结果。结果29例WD患者中，男18例，女11例，中位年龄25．9岁（5～71岁）。临床表现乏力18例（62．1％），腹胀、皮肤瘙痒各4例（13．8％）；体征包括：肝大11例（37．9％），脾大15例（51．7％）和腹水4例（13．8％）等。实验室检查示29例WD患者均有肝功能异常及24h尿铜升高（100．O％），24例铜蓝蛋白降低（82．8％），8例K-F环阳性（27．6％）。19例患者接受ATP7B基因检查，基因突变位点有外显子5、8、11、12、16和18。肝组织病理学特点：早期为肝细胞脂肪变性（大小泡混合性），铜染色阳性或阴性，肝小叶内可无明显炎症；慢性肝炎期主要表现为汇管区炎细胞浸润、胆管上皮变性，汇管区周围肝细胞胆盐淤积性改变伴铜颗粒沉积，小叶内灶性炎症；肝硬化期表现为汇管区扩大纤维化，宽阔间隔内铜沉积及小胆管破坏、增生、间隔周围肝细胞胆盐淤积性改变及大量铜颗粒沉积。临床确诊6例，临床＋病理诊断4例，临床＋肝脏病理＋基因检测诊断19例。结论WD单靠临床诊断漏诊率高；肝脏组织学中汇管区周围肝细胞胆盐淤积性改变较常见，有提示作用；ATP7B基因检测外显子16杂合突变较常见。临床＋基因检测＋肝脏病理可提高早期诊断率，减少误诊和漏诊率。Objective To summarize the clinicopathological manifestations of Wilson disease （WD） so as to improve its recognition. Methods A total of 29 WD cases were retrospectively analyzed, including clinical presentations, liver function test, serum ceruloplasmin, 24 hour urinary copper excretion, ATP7B gene analysis and liver histology. All cases were diagnosed from January 2007 to October 2012 at Third Hospital of Hebei Medical University and China-Japan Friendship Hospital. Results There were 18 males and 11 females with an average age of 25. 9 years. The major clinical symptoms included fatigue （n = 18, 62. 1% ） , abdominal distension （n = 4,13.8% ） and pruritus （n = 4, 13.8% ）. The common physical signs were hepatomegaly （ n = 11, 37.9% ）, splenomegaly（ n = 15, 51.7% ） and ascites （ n = 4, 13.8% ）. The laboratory examinations included abnormal liver function （ n = 29, 100% ） , high level of 24-hour urinary copper excretion （n = 29, 100. 0% ） , low serum ceruloplasmin （n =24, 82. 8% ） and Kayser-Fleischer ring （n=8, 27.6% ）. ATPTB gene mutations were at exons 5, 8, 11, 12, 16 and 18. The earliest histologic abnormalities of liver included steatosis （both microvesicular and maerovesicular）. Timm＇s stain showed positive or negative staining. There was no or focal hepatoeellular necrosis in liver. During chronic hepatitis phase, the major changes included inflammatory cells infiltration in portal area with biliary epithelium degeneration. The periportai area hepatic eells were swollen, cytoplasm slightly stained and aceompanied with some copper particles deposition and eholestic changes. There were many spotty or focal lesion of necrosis in liver. During cirrhotic phase, portal area became enlarged by fibrotic tissue, numerous copper particles deposited in wide fibrous septa and small bile duets were damaged and became proliferative. Hepatocytes around fibrous interval showed eholestatie changes and contained many copper particles. They diagnosed on the basis of clinical

关 键 词：肝豆状核变性 血浆铜蓝蛋白 突变 基因 ATPTB 

分 类 号：R742[医药卫生—神经病学与精神病学]