原发性胆汁性肝硬化临床病理分析

目的探讨原发性胆汁性肝硬化(PBC)的临床病理学特征及其发病机制. 方法对30例PBC患者,其中早期组(Scheuer分期Ⅰ、Ⅱ期)19例,晚期组(Scheuer分期Ⅲ、Ⅳ期)11例,进行临床、病理和血清学研究分析.以标志性抗体进行免疫组织化学染色,对肝组织中树突状细胞(DC)和肝星状细胞(HSC)的变化进行观察研究. 结果 30例PBC患者中,男女之比为15,平均年龄为40.6岁.血清总胆红素(TBil)均值(95.9±88.5)μmol/L,碱性磷酸酶(ALP)均值(537.2±339.2)U/L,谷氨酰转肽酶(GGT)均值(582.0±351.2)U/L,抗线粒体抗体(AMA)阳性率为73.3%,GGT水平与AMA滴度成明显正相关(r＝0.778,P＝0.000).PBC晚期黄疸、肝大明显(χ2值分别为5.182和13.659,P值分别为<0.05和0.001).病理改变主要为汇管区及其周围病变,早期表现为小叶间胆管的毁损,小胆管的明显增生;晚期主要为肝纤维化及肝硬化.肝细胞内色素颗粒沉积、肝细胞的玫瑰花形排列、增生的小胆管侵蚀小叶界板、肉芽肿形成、淋巴滤泡样结构、泡沫细胞等病变在早、晚期均可出现,但后二者早期较晚期多见(t值分别为4.489和4.019,P值均<0.05).铁、铜沉积不同程度增多.DC、HSC主要位于汇管区,尤其是损伤胆管的周围. 结论 PBC患者AMA水平与胆红素及转氨酶间无直接关系.增生的小胆管上皮细胞可能已含有免疫抗原,为免疫攻击的直接靶细胞,而DC作为抗原递呈细胞在PBC的病理机制中可能起重要作用.

Clinical and pathological analysis on characteristics of primary biliary cirrhosis

OBJECTIVES: To explore the clinical and pathological features and the pathogenesis of primary biliary cirrhosis (PBC) in Chinese Mainland. METHODS: 30 PBC patients were divided into the early group (Scheuer stage I and II, 19 patients) and the late group (Scheuer stage III and IV, 11 patients). The data of clinics and serology were analyzed, and the pathological features of the liver tissues were characterized. The changes of dendritic cells (DCs) and hepatic stellate cells (HSCs) were studied by immunohistochemistry. RESULTS: In all the PBC patients, the rate of the male to the female was 1 to 5, and the average age was 40.6 years. The mean levels of TBiL, ALP and GGT in the sera were (95.9+-88.5) micromol/L, (537.2+-339.2) U/L, and (582.0+-351.2) U/L, respectively. 73.3% patients showed AMA positive, and the level of GGT was positively correlated with the AMA level according to the result of statistical analysis (r=0.778, P=0.000). The symptoms of jaundice and hepatomegaly were presented more commonly in the late group than those in the early group (chi2=5.182, P<0.05; chi2=13.659, P<0.01, respectively). The main changes of morphology of PBC located in portal tracts. The liver tissues in the early stage of PBC showed the damage of bile ducts and obvious proliferation of small bile ducts. The granulomas, the lymphoid follicles and the foamy cells were found in the liver tissues of PBC (2/19 patients, 12/19 patients, and 10/19 patients in the early stage respectively, while 0/11 patients, 4/11 patients, and 3/11 patients in the late stage respectively). There was significant difference between the early stage and the late stage in presence of the lymphoid follicles and the foamy cells (t=4.489, P<0.05; t=4.019, P<0.05, respectively). The biliary pigmentary particles were mainly accumulated in the liver cells around the portal tracts in 90.0% PBC patients, and the accumulation of copper and iron increased, compared with that in normal specimens. The DCs and HSCs located mainly in the portal tracts, especially around the damaged bile ducts. CONCLUSIONS: There are some clinical and pathological characteristics in the patients with PBC. The level of AMA has no direct relationship with the level of transaminase or bilirubin. The proliferated bile ductules may express the antigens which maybe the target of immune attack. As an antigen-presenting cell, DCs may play an important role in the pathogenesis of PBC.