血色病肝脏铁沉积的病理特点分析

Pathology of hepatic iron deposition in hemochromatosis

目的 探讨不同原因造成的血色病肝脏铁沉积程度、分布特点及其与组织学改变的关系.方法 对31例血色病患者肝活体组织标本进行HE、网状纤维、胶原纤维及普鲁士蓝染色,组织学改变及铁沉积情况分别用Ishak评分及Deugnier评分系统评估,部分病例留取外周血进行血色病及相关遗传代谢疾病基因检测.统计处理均使用SPSS 19.0统计软件,用t检验比较两组数据之间的差异. 结果 31例血色病中,1例为遗传性血色病基因突变的原发性血色病伴Gilbert综合征、4例Gilbert综合征铁沉积均主要位于Ⅰ区肝细胞内,围绕汇管区,Ⅰ区至Ⅲ区铁沉积递减,炎症及纤维化程度均较轻;1例Ⅰ型遗传性血色病基因突变的原发性血色病伴乙型肝炎铁沉积与8例病毒性肝炎铁沉积相似,均在小叶内弥漫分布,有明显的肝细胞、肝窦及汇管区细胞铁沉积,炎症及纤维化轻重不一;5例血液系统疾病铁沉积也主要位于Ⅰ区,但肝细胞及肝窦、汇管区细胞均有铁沉积,炎症及纤维化程度较轻;5例脂肪性肝病及5例药物性肝损伤铁沉积量较少,主要位于肿胀或气球样变的肝细胞内;2例食物中铁摄入过多,铁在小叶内弥漫分布,肝细胞、肝窦及汇管区细胞均有.非肝细胞铁沉积评分、肝脏炎症活动度评分和纤维化程度评分：有遗传性疾病患者和无遗传性疾病患者分别为4.09±4.01和8.75±6.54、2.45±1.13和8.20±4.15、0.91±0.30和2.70±1.38,t值分别是-2.45、-5.81、-5.57,P值分别＜0.05 ～＜0.01.结论 不同原因造成的血色病肝脏铁沉积模式不同,铁在肝内沉积程度、分布特点的分析有助于病因诊断及预后评估.

Objective To identify the type of iron deposition and describe its amount,distribution and associated lesions,in order to support an etiologic diagnosis for hemochromatosis.Methods Hematoxylineosin （HE） stain,reticular fiber stain,Masson＇s stain and Perl＇s iron stain were used to assess liver biopsies from 31 patients with hemochromatosis.The Ishak scoring system and Deugnier scoring system were used to assess the histological change in liver and to semi-quantify the excess of hepatic iron.Genetic testing results were received from a portion of the patients and used in analysis.Results One patient had hereditary （-HFE） hemochromatosis complicated with Gilbert＇s syndrome,for which the pattern of iron deposition was similar to that of the four patients with Gilbert＇s syndrome.Iron accumulation appeared as fine granules predominating at the biliary pole of cells and was distributed throughout the lobule with a decreasing gradient spanning from the periportal to centrolobular areas.Mild chronic inflammation was found to be commonly associated with low stage fibrosis.One patient had HFE hemochromatosis complicated with hepatitis B virus infection,and the pattern of iron deposition resembled that in the eight patients with viral hepatitis,wherein the deposition was mainly in the sinusoidal cells and/or portal macrophages.Histological grading and fibrosis staging differed among patients.The five patients with blood disordered showed iron accumulation mainly in the periportal hepatocytes,but mesenchymal iron deposits were also present.The grade of inflammation,as well as of fibrosis,was mild.The five patients with alcoholic disease and the five patients with drug-induced hepatitis showed hepatic iron deposition in swollen or ballooned hepatocytes.The two patients with excessive iron supply showed iron deposition localized within the parenchymal and mesenchymal cells.Conclusion Etiologic diagnosis of hemochromatosis relies on both the type of iron deposition and the nature of associated lesions.Liver biopsy is necessary for both diagnosis and prognosis.