摘要目的 探讨糖尿病肝微血管病变及糖尿病肝硬化症(DHS)临床及病理组织学特征.方法 选择性收集120例2型糖尿病患者的尸体解剖肝脏材料为糖尿病组,除外其他已知病因引起的肝纤维化及肝硬化病例.48例同年代、性别、同年龄组非糖尿病患者为对照组.观察肝脏标本中微血管、汇管区、肝窦的病理形态学改变.结合组织化学过碘酸-雪夫(PAS)染色、唾液酶消化-PAS、Van Gieson(VG)染色、弹力染色、Masson 三色染色及免疫组织化学染色进行研究.收集符合DHS诊断患者的临床资料并进行分析.结果 (1)2型糖尿病组120例患者均为老年男性,出现微血管病变65例,占54.2%(65/120).微血管病变表现为:小叶间动脉(微动脉,管腔直径<100 μm)内膜内皮细胞脱落、嗜伊红物质沉积、内膜偏心性增厚,管腔狭窄至闭塞;中膜平滑肌增生或萎缩;外膜纤维组织增生,部分呈洋葱皮样增厚.对照组16.7%(8/48)的患者出现微血管病变,两组比较差异有统计学意义(x2=19.622,P<0.01).(2)55.8% (67/120)的患者汇管区纤维化、硬化,表现为玻璃样变的胶原纤维在小叶间动脉、静脉及小叶间胆管周沉积,使汇管区扩大,进而使汇管区三联管萎缩、消失,形成硬化的汇管区.对照组22.9%(11/48)的患者出现汇管区纤维化、硬化表现,两组比较差异有统计学意义(x2=14.936,P<0.01).(3)2型糖尿病组符合DHS诊断17例,占14.2% (17/120).HE染色显示纤维化、硬化的汇管区呈蜘蛛丝样,沿肝板向周围肝组织延伸或为肝窦内出现非区带性嗜伊红物质沉积,肝窦内纤维化、硬化.Masson三色及VG染色显示肝窦内胶原纤维沉积,免疫组织化学染色显示Ⅳ型胶原、平滑肌肌动蛋白、CD34肝窦内阳性.对照组未见肝窦内硬化病例.17例符合DHS病理改变的患者中13例伴有明显的肝微血管病变;17例均伴有汇管区纤维化、11例伴汇管区硬化改变;10例同时伴有糖尿病肾病改变.肝功能检查中,7例出现碱性磷酸酶升高,其中3例同时伴有丙氨酸转氨酶及天冬氨酸转氨酶轻度升高.结论 糖尿病肝微血管病变在2型糖尿病老年男性患者中较为常见;DHS与糖尿病肝微血管病变相关;汇管区纤维化、硬化可能为DHS的早期或伴发组织形态学改变;DHS为2型糖尿病并发症之一.
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abstractsObjective To study the clinicopathological features of diabetic microangiopathy in liver and diabetic hepatosclerosis (DHS) of elderly male with type 2 diabetes mellitus (T2DM).Methods One hundred and twenty autopsy eases with T2DM (diabetic group) and contemporary 48 cases,non-diabetic and glucose tolerance abnormal,matched by gender and age (control group) were selected in the study.Cases with the cirrhosis and fibrosis of liver caused by other foregone etiological factors were excluded.The histopathological changes of microangiopathy in liver,hepatic portal areas and hepatic sinusoid were investigated by HE staining,histochemical and immunohistochemical stain methods.The clinical data of diagnostic DHS cases were analyzed.Results (1) Microangiopathy was observed in 54.2% (65/120) cases of diabetic group.Histological features:microangiopathy was found in interlobular arteries (especially in arteriole,the lumen diameter < 100 μm),which included endothelial denudation,eosinophilic material deposition in the tunica intima of artery,and eccentric intimal thickening.The smooth muscle fibers of tunica media were hyperplastic or atrophy.Fibroplasia and collagen deposition were found in the tunica adventitia of artery.Arterial lumina showed stenosis and occlusion.Microangiopathy was seen in 16.7% (8/48) cases of the control group.There was statistically significant difference between the two groups (x2 =19.622,P <0.01).(2) The fibrosis and sclerosis of portal areas were detected in 55.8% (67/120) cases of T2DM group.Hyaline collagen fiber tissues was deposited around interlobular arteries,interlobular veins and interlobular bile ducts,resulting in enlargement of the portal area and the secondary atrophy and disappearance of portal triad.The fibrosis and sclerosis of portal areas were detected in 22.9% (11/48)cases of the control group.There was a statistically significant difference between the two groups (x2 =14.936,P <0.01).(3) The pathological features of 14.2% (17/120)cases were consistent with the diagnosis of DHS.The fibrous tissue extended from fibrosis or sclerosis of portal areas,or eosinophilic material deposition in the hepatic sinusoid in non-zonal pattern.The results of histochemical staining showed collagen fiber deposition in hepatic sinusoid.Stainings for Collagen Ⅳ,SMA,CD34 were found in the hepatic sinusoid.The sclerosis of hepatic sinusoid was not detected in any case in the control group.Overall,13/17 and 11/17 DHS cases had liver microangiopathy and portal areas sclerosis respectively.Diabetic nephropathy was seen in 10 of 17 DHS cases.Among the 17 cases,7 cases showed ALP elevation,of which there were 3 cases with ALT and AST mild elevation.Conclusions Diabetic microangiopathy is common in the liver of elderly men with T2DM.And DHS is associated with diabetic microangiopathy.Fibrosis and sclerosis of portal areas may be the early or concomitant changes of DHS on histological ground.DHS is one of the complications of T2DM.
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