先天性肝纤维化临床及病理学特点分析

目的探讨先天性肝纤维化(congenital hepatic fibrosis, CHF)的临床和病理特征。方法收集2014—2021年中山大学附属第三医院病理科CHF病例12例, 进行临床及病理特征分析。结果 12例患者中, 男性6例, 女性6例, 年龄5～24岁, 中位发病年龄13岁。临床表现为发热、呕血/便血、牙龈/鼻腔出血、黄疸、乏力。病理特征为肝组织被大小不等的纤维间隔分隔成结节状, 汇管区纤维组织明显增生, 汇管区中央的胆管扩张, 周边小胆管增生, 炎细胞浸润不明显。结论 CHF好发于儿童或年轻人, 以汇管区纤维化扩大及胆管增生、扩张为主要病理学改变。肝活检是诊断CHF的首选方案。     

孕鼠肝内胆汁淤积症对母鼠和胎鼠心脏的影响

目的探讨孕鼠肝内胆汁淤积症对母鼠和胎鼠心脏的影响。方法应用雌、孕激素建立妊娠肝内胆汁淤积大鼠模型,光镜和电镜观察母鼠和胎鼠心脏的病理改变。结果（1）胆淤组和对照组比较,孕鼠血清丙氨酸转氨酶（ALT）、门冬氨酸转氨酶（AST）、总胆汁酸（TBA）的差异有显著性（P〈0．01）。（2）胆淤组孕鼠肝脏光镜下见部分肝细胞有颗粒样变性和空泡变性,电镜下见肝组织中毛细胆管扩张,毛细胆管及肝细胞内见高电子致密物沉积。（3）胆淤组孕鼠胎盘光镜下见部分滋养细胞颗粒样变性和空泡变性。（4）胆淤组孕鼠心脏光镜下见心肌组织中局灶性心肌细胞颗粒样变性。（5）胆淤组胎鼠心脏光镜下见心肌组织中心肌细胞广泛空泡变性;电镜下见胎鼠心肌细胞内高电子致密物沉积,部分肌丝断裂,肌节模糊,细胞内线粒体水肿,脱髓鞘样改变。结论孕鼠肝内胆汁淤积症时高胆汁酸血症对母鼠和胎鼠心肌细胞均有明显的毒性作用,尤其以胎鼠心肌细胞病变更为严重。     

MRP2在胆汁淤积中的研究进展

胆汁淤积（cholestasis）是肝内外各种疾病所引起的胆红素代谢障碍的综合性病理过程,胆道梗阻、肝叶切除、肝移植、内毒素血症、药物性肝脏损害、原发性胆汁性肝硬化、原发性硬化性胆管炎等疾病常并发胆汁淤积的病理改变。多药耐药相关蛋白2（Mu ltidrug resistance-assoc iated prote in 2,MRP2）又名毛细胆管面多特异性有机阴离子转运子（thecanalicu larmu ltispec ific organ ican ion transporter,cMOAT）与胆汁淤积密切相关,是近年来的研究热点。     

乙酸消融胆道的实验研究

目的探讨乙酸消融家兔胆道后病理及肝功改变,为临床应用消融栓塞胆道治疗肝内胆管结石提供实验依据。方法观察家兔右外叶胆道于25%至5%浓度乙酸消融后肝脏功能状态、肝组织病理改变和术后存活情况。结果25%乙酸胆道消融造成右外叶肝脏大块坏死,仅肝叶边缘有少量存活肝组织。20%乙酸胆道消融后近肝门部肝实质以汇管区为中心的坏死,肝叶中部见汇管区及周围少量肝细胞坏死,肝叶边缘见汇管区点状坏死。15%乙酸胆道消融后近肝门部见汇管区及周围少量组织坏死,肝叶中部及边缘组织见胆管无明显改变,周围组织点状坏死。10%乙酸胆道消融后近肝门部汇管区胆管坏死,周围充血,肝叶中部胆管上皮完整,周围组织充血,肝叶边缘胆管完整,周围少量肝细胞肿胀。5%乙酸胆道消融后近肝门部胆管上皮坏死,肝叶中部胆管上皮完整,仅充血或少量肝细胞肿胀。结论20%为乙酸消融胆道较理想的浓度。     

肝血管阻塞在乙型肝炎肝硬变中的作用

目的；揭示乙型肝炎肝内血管阻塞在肝硬变发展听作用。方法：对３５０例不同类型的肝硬变标本进行了ＨＥ、组化、免疫组化及超微结构的观察。结果：（１）肝内血管阻塞性病变是乙型肝炎肝硬变的组织病理学特征，有血栓、炎性栓塞、栓塞性静脉炎、血管闭塞性纤维化等表现；（２）血管阻塞性损伤能引起血管、胆管及弹力纤维增生；（３）血管阻塞的大小与肝实质变性坏死密切相关，严重者可引起肝梗塞；（４）血管阻塞－血管纤维化是构成     

实验性肝纤维化大鼠层粘连蛋白含量的变化

用四氯化碳诱导大鼠肝脏纤维化，采用酶联免疫吸附法（ＥＬＩＳＡ）检测大鼠血清和肝组织匀浆中层粘连蛋白（ＬＮ）含量，并分析ＬＮ与肝功能及肝组织学病理改变之间的关系。结果发现，血清ＬＮ在大鼠肝脏受损伤后早期即出现增加，并随肝组织损害程度的加重而递增，与肝功能改变及病理损伤有一定相关性。肝匀浆中ＬＮ含量在肝损伤晚期才升高，与肝功能指标没有相关性，提示，血清ＬＮ含量改变是反映肝脏损伤的敏感指标，可用于动态观     

Caroli病的临床病理学观察

目的：探讨Caroli病的临床病理特征。方法：复习7例Caroli病全部临床,影像资料和手术记录,对肝脏病变切除标本行病理常规切片、HE染色、光镜观察。结果：本病发病年龄3－62岁,平均38岁,男女比为1：25。临床上以右上腹疼痛为首发症状,2例合并胆管癌、胆囊癌,无1例在术前被确诊。影像学提示肝内胆管有不同程度扩张和纤维化、病理上表现为肝内胆管囊性扩张、上皮增生呈乳头状,伴有胆管周围纤维组织细胞增生、变性和大量炎细胞浸润。结论：Caroli病是少见的生天性肝脏病变,临床易误诊为胆囊炎、胆石症、确诊依赖于病理和影像学检查。     

肝脏纤维化与免疫调控

肝纤维化是慢性肝病的晚期病理改变和临床转归之一,是脏器纤维化的典型例证。肝脏具有异于其他脏器组织解剖学和免疫学等方面的特点。肝脏血管网密集,增生的结缔组织可引起其血流异常,如循环短路,可导致肝实质细胞的继发性坏死和一系列病理生理改变~([1])。肝脏供血丰富,是机体进行物质交换和代谢的中心,易与外来异物抗原接触,从而激活细胞免疫系统,产生对纤维母细胞有促进效应的活性物质。近年的研究表明,机体细胞免疫系统对肝脏纤维化起着关键的调节作用。     

Gordon-Sweets银氨染色和Masson三色套染技术在肝穿刺病理诊断中的应用

正肝穿刺活体组织检查(简称肝穿刺活检)是一种在B超、CT的定位和引导下经皮肤穿刺获取少量肝脏标本,经过处理后行病理组织学、免疫组化、特殊染色等,在镜下观察肝脏组织和细胞形态的一门技术[1]。在肝穿刺病理诊断工作时,为了解肝脏的炎症和纤维化程度,常用的特殊染色方法     

肝内胆汁淤积症胎鼠脑组织中NPY的表达定位及意义

目的观察妊娠肝内胆汁淤积症(ICP)孕鼠肝脏、胎鼠脑组织结构变化;分析神经肽Y(NPY)在妊娠期肝内胆汁淤积症(ICP)胎鼠脑组织中的表达及意义。方法选择孕15 d SD大鼠,用孕酮及乙炔雌二醇建立孕鼠ICP模型,观察孕鼠肝脏和胎鼠脑组织的病理变化;应用免疫组织化学染色方法及图像分析检测ICP孕鼠(20例,实验组)及正常孕鼠(20例,对照组)脑组织中NPY的表达及定量。结果 ICP孕鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆酸(TBA)明显升高;光镜下见部分肝细胞有颗粒样变性和空泡变性。电镜下见肝组织中毛细胆管扩张、微绒毛肿胀,毛细胆管周围肝细胞内见电子致密物沉积。胎鼠脑组织疏松,空泡样变性明显,部分细胞溶解,甚至消失。实验组胎鼠脑组织NPY表达免疫阳性神经元主要位于海马区,免疫阳性细胞被染成棕黄色,免疫阳性颗粒主要分布在胞质和细胞膜表面。对照组海马区仅少部分细胞膜着色或无免疫着色。胎脑组织NPY的免疫组化结果用图像分析仪测定,结果显示:实验组NPY平均光密度值(1.0486±0.0182)明显高于对照组的(0.6297±0.0278),两者比较有显著性差异(P<0.05)。结论 ICP母鼠肝脏及胎鼠脑组织有明显病变,胎鼠脑组织中的NPY表达升高,可能与胎脑组织受损有关。     

Clinicopathological study of a hilar nodule in the livers of long-term survivors with biliary atresia

With the application of liver transplantation for patients with biliary atresia (BA), we have had the opportunity to review the clinicopathologic features of the native livers from 10 transplanted BA patients. A single large nodule at porta hepatis (hilar nodule) was noted in three of 10 patients, and an ill-defined nodule-like lesion at porta hepatis was present in two other patients. The three BA patients with hilar nodules were long-term survivors, compared to the patients with nodule-like and those without nodules. The hilar nodules measured between 5.0 cm and 8.0 cm and histologically, they were partly surrounded by fibrous septa with relatively well-preserved liver architectures and fewer inflammatory cells at the portal triads when compared to the surrounding cirrhotic lesions. No nuclear or cellular atypia was observed. Proliferating cell nuclear antigen labeling index was higher in the surrounding cirrhotic lesions than the hilar nodules. The nodule-like lesions at porta hepatis also showed similar light microscopic and immunohistochemical features as the hilar nodules. These hilar nodules did not seem to contain any malignant potential. The benign histology with relatively well-preserved liver architecture and the preferential site of occurrence at porta hepatis where bile seemed to flow more smoothly, suggested possible residues of less-affected hepatic tissues.     

The developing human biliary system at the porta hepatis level between 11 and 25 weeks of gestation: A way to understanding biliary atresia. Part 2

In biliary atresia, inflammation and destruction of extra-hepatic and intrahepatic bile ducts with eventual fibrous obliteration occurs, causing neonatal obstructive jaundice. The onset of the disorder may start antenatally and progress after birth, and the porta hepatis is a constant site of involvement. To date, little is known about the intrauterine development of the bile ducts at the porta hepatis. The present work gives an account of the developmental pattern of bile ducts at the level of the porta hepatis in the normal human fetus from the 11th to the 25th weeks of gestation. It has been observed that the proximal portion of the hilar bile ducts derives from the intrahepatic biliary ductal plate. This occurs following a predictable remodeling sequence by which, from many ductal plate-derived ductules, those destined to become definitive bile ducts are enveloped in a concentric cuff of mesenchyma. Those which are not are deleted. The distal portions of the right and left main hepatic ducts develop from the extrahepatic bile duct. There was no gestational period in which the extrahepatic bile duct and the intrahepatic blliary system were separated. Furthermore, the developing intrahepatic bile ducts maintain lumina continuity with the common bile duct from the start of organogenesis. Biliary atresia may result from: (i) failure to establish a definitive type of bile duct; (ii) leakage of bile from primitive bile ducts resulting in an interstitial inflammatory reaction in the adjacent mesenchyma; and (iii) continuous proliferation of primitive bile ducts at the level of the porta hepatis beyond the 25th week of gestation, as a failed compensatory mechanism.     

Intrahepatic biliary cysts in congenital biliary atresia

A case of pronounced cystic dilatation of the intrahepatic bile ducts with biliary atresia is presented. Intrahepatic biliary cysts have been described in biliary atresia, although, as far as we are aware, none as extensive as in this case. The cysts represent end-stage obstruction with irreversible liver injury; thus, drainage of these cysts does not alleviate the condition. The differential diagnosis includes Caroli's disease, congenital hepatic fibrosis, and polycystic liver disease.     

Hilar biliary plexus in human liver. A comparative study of the intrahepatic bile ducts in man and animals

A comparative study of the hepatic bile ducts of man and laboratory animals was made by means of scanning electron microscopy of biliary tract casts. In man, the large intrahepatic bile ducts at the hilum have many irregular side branches and pouches which are all situated in one plane corresponding anatomically to the transverse fissure (porta hepatis). At the bifurcation, some of the side branches from two or three bile ducts communicate with each other. The anastomosing plexus so formed provides communications between the main bile ducts. Bile ducts of the rhesus monkey show a similar but less well developed structure. In the pig, many pouches are observed around not only large but also small bile ducts. No such structures are observed in dog, guinea pig, or rabbit bile ducts. These irregular side branches and pouches correspond to the "vasa aberrantia" and "parietal sacculi" described by L. S. Beale (The Liver. Lecture on the Principles and Practice of Medicine, p 47. London, Churchill, 1889), and they may store and modify bile. The plexus described in man in this report may provide an anatomical basis for incomplete biliary obstruction without cholestasis. A role in biliary atresia and in Caroli's disease is also raised.     

The pattern of differentially expressed genes in biliary atresia

Biliary atresia is a progressive obliterative cholangiopathy, but the etiology of this disorder remains uncertain. Identifying genes specifically expressed in biliary atresia and analyzing the pattern of expression may lead to a better understanding of the pathogenesis. Liver tissues were taken from a recipient with biliary atresia and a normal donor during liver transplantation. Total RNA was extracted from each sample and reversely transcribed to cDNA. Then radiolabeled cDNA probe pools were made by random primed DNA labeling method and used for screening of differentially expressed genes by hybridizing with expressed sequence tags (EST) dot blot panel. Northern blot hybridization was done to confirm that these genes are also differentially expressed in other liver tissues. Among 1730 EST clones, 26 cDNA clones were significantly overexpressed in biliary cirrhosis, while 2 clones were significantly decreased in biliary atresia. By Northern blot hybridization, the results of tissue inhibitor of metalloproteinase (TIMP)-1 and IGFBP-2 were well correlated with differential EST screening (DES). This study identified the pattern of differentially expressed genes in the biliary cirrhosis due to biliary atresia using DES technique.     

Extrahepatic biliary atresia. Morphological study of 98 biliary remnants

Histologic examination was performed on 98 biliary remnants. Classification into three types was made according to the presence of epithelial structure; biliary and glandular formations had to be separated. Atretic lesions were predominantly observed at the pars inferior of the remnants. These histological findings agree with the theory of a dynamic ascending process that leads to progressive, complete destruction of the biliary and glandular structure, although main ducts may remain preserved by the vicinity of the porta hepatis. Classic clinical data suggest that the damage is initiated in utero. The lesions certainly progress after birth; in some cases the fibrotic process of the remnant may have already reached completion at birth, whereas in some others it may become clinically evident after birth.     

Distortion in TGFβ1 peptide immunolocalization in biliary atresia: Comparison with the normal pattern in the developing human intrahepatic bile duct system

Biliary atresia is an important cause of neonatal obstructive jaundice in which there is inflammation, sclerosis and eventual obliteration of the bile duct system. Its onset may be antenatal, affecting the normal development of the biliary system. The intrahepatic biliary system is derived from the ductal plate, a sheath of cuboidal epithelium that appears at the hepatocyte-mesenchymal junction around the portal vein branches at 6 weeks gestation. This epithelial structure is moulded into a network of tubular bile ducts by the proliferating mesenchyme. Certain portions of the ductal plate are selected to become definitive bile ducts, while redundant biliary epithelium is deleted. The molecular dynamics controlling the intra-uterine development of the biliary system in humans are not yet clearly understood. Transforming growth factor-β1 is a cytokine that stimulates mes-enchymal proliferation and inhibits epithelial growth, and has been shown to be important in organogenesis. In the present study, the pattern of TGFβ1 peptide immunolocalization was investigated with the aid of computerized image analysis, in normal human bile duct development and in biliary atresia. TGFβ1 peptide was detected within hepata-cytes and ductal plate epithelium from 7 weeks gestation; increased TGFβ1 immunoreactivity was present within the epithelium of developing bile ducts at 13 weeks gestation, and apical polarization of the cytokine was observed from 16 weeks gestation. In biliary atresia, the TGFβ1 immunoreactivity pattern within the bile duct structures at the porta hepatis and within intrahepatic portal tracts resembled that of the primitive ductal plate, and there was no significant apical polarization. This may indicate a developmental arrest in the normal ductal plate remodelling process in biliary atresia, and suggests an underlying epithelial-mesenchymal interactive disorder.