Embryology of Extra‐ and Intrahepatic Bile Ducts,the Ductal plate

In the human embryo, the first anlage of the bile ducts and the liver is the hepatic diverticulum or liver bud. For up to 8 weeks of gestation, the extrahepatic biliary tree develops through lengthening of the caudal part of the hepatic diverticulum. This structure is patent from the beginning and remains patent and in continuity with the developing liver at all stages. The hepatic duct (ductus hepaticus) develops from the cranial part (pars hepatica) of the hepatic diverticulum. The distal portions of the right and left hepatic ducts develop from the extrahepatic ducts and are clearly defined tubular structures by 12 weeks of gestation. The proximal portions of the main hilar ducts derive from the first intrahepatic ductal plates. The extrahepatic bile ducts and the developing intrahepatic biliary tree maintain luminal continuity from the very start of organogenesis throughout further development, contradicting a previous study in the mouse suggesting that the extrahepatic bile duct system develops independently from the intrahepatic biliary tree and that the systems are initially discontinuous but join up later. The normal development of intrahepatic bile ducts requires finely timed and precisely tuned epithelial–mesenchymal interactions, which proceed from the hilum of the liver toward its periphery along the branches of the developing portal vein. Lack of remodeling of the ductal plate results in the persistence of an excess of embryonic bile duct structures remaining in their primitive ductal plate configuration. This abnormality has been termed the ductal plate malformation. Anat Rec, 291:628–635, 2008. © 2008 Wiley‐Liss, Inc.     

左外叶活体肝移植的解剖学研究

目的：模拟左外叶活体肝移植门静脉、肝动脉和胆管的切取方法。方法：解剖正常人肝脏标本30具，观察肝脏铸型标本30具，测量门静脉、肝动脉及胆管长度、管径及属支或分支分布情况。结果：左外叶门静脉的血供来自门静脉左支，主要为左外叶上段门静脉支、左外叶下段门静脉支；动脉主要来源于肝固有动脉、肝左动脉、肝中动脉，偶有迷走动脉支；胆道引流属支有左外叶上段胆管支、左外叶下段胆管支。结论：左外叶解剖变异较多，活体取肝前应仔细研究其结构特点，设计合理的切取模式；对门静脉、肝动脉和胆管支需行必要的整形，以便与受体相应的管道进行吻合。     

Intraductal oncocytic papillary neoplasm of the liver

A very rare case of intraductal oncocytic papillary carcinoma of the liver is reported. A 63-year-old Japanese man was admitted to our clinic because of abdominal pain and jaundice. Imaging techniques revealed a unilocular cystic neoplasm of 14 cm diameter in the medial segment of the left hepatic lobe. Combined percutaneous and endoscopic retrograde cholangiographies revealed the unilocular cystic neoplasm contained a lot of mucus and communicated with the left segmental intrahepatic bile duct, and that mucus filled the left segmental and hepatic ducts. Left lobectomy was performed. The postoperative course was good, and the patient is free of disease 30 months after operation. Pathological examination revealed that the cavity of the neoplasm was continuous with the left segmental intrahepatic bile duct, and that a lot of mucus was present in the neoplasm, as well as in the left segmental and hepatic ducts. The neoplasm consisted of papillary growth of atypical epithelial cells with oncocytic changes. Atypical goblet cells were also recognized. No invasion into the surrounding liver was noted. Non-tumorous intrahepatic bile ducts near the lesion occasionally showed epithelial dysplasia and contained a lot of mucus. Immunohistochemically, the tumor cells were rich in mitochondria and were immunoreactive for cytokeratins 7, 18 and 19, carbohydrate antigen 19-9, and hepatocyte-specific antigen. Some tumor cells were immunoreactive for pancreatic alpha-amylase and lipase. Ultrastructurally, the tumor cells showed numerous mitochondria and mucus droplets. Intraductal neoplasm communicating with the intrahepatic bile ducts has rarely been reported. The present case suggests that intraductal oncocytic papillary neoplasm, as described in the pancreas, may also occur in the intrahepatic bile ducts, and that such hepatic intraductal neoplasm may express hepatocellular and pancreatic acinar phenotypes.     

'Undifferentiated progenitor cells' in focal nodular hyperplasia of the liver

Focal nodular hyperplasia is a tumour like lesion, characterized by a central fibrous scar with irradiating fibrous septa that surround hyperplastic nodules and contain multiple bile ductules. The origin of the bile ductular structures is not clear. Recently, we found evidence for the existence of human counterparts of rat oval cells (potential stem cells) that have the ability of differentiating towards both bile duct cells and hepatocytes. These cells were found in regenerating human liver as well as in chronic cholestatic conditions. Because cholestatic features are seen in focal nodular hyperplasia, we initiated an immunohistochemical study on 23 surgical specimens using antibodies specific for cytokeratins 7 and 19 (bile duct type cytokeratins), OV6 (rat oval cell marker), chromogranin-A (shown to be positive in reactive bile ductules and human oval-like cells) and neural cell adhesion molecule—NCAM (shown to be positive in reactive bile ductules) to investigate whether ‘undifferentiated progenitor cells’ are also present in focal nodular hyperplasia. Electronmicroscopy was applied in five cases. Bile ductules invariably showed immunoreactivity for CK7 and 19, OV6, chromogranin-A and NCAM. In addition, small individual cells with an oval nucleus and a small rim of cytoplasm, in the vicinity of the septa, were immunoreactive for chromogranin-A, CK7 and 19 and OV6. These cells were hardly recognizable on routine light microscopy. Clusters of periseptal hepatocytes, seemingly in continuity with bile ductular structures, had a transitional phenotype: they stained positive for chromogranin-A, CK7 and OV6 and sometimes formed liver cell rosettes. The number of OV6-positive hepatocytes was greater than the number of chromogranin-A and CK7 positive hepatocytes. This indicates that, in human liver, OV-6 is not purely a marker of progenitor cells. Ultrastructurally, small immature cells, highly resembling rat oval cells, were recognized in the vicinity of septa. In addition, transitional cells displaying characteristics both of hepatocytes and bile duct cells were also present. These results confirm the presence of ‘undifferentiated progenitor cells’ in focal nodular hyperplasia and suggest that the ductular reaction in these lesions results, at least partly, from activation of these cells.     

Mucin-histochemical and immunohistochemical profiles of epithelial cells of several types of hepatic cysts

Summary Epithelial cells of several types of hepatic cysts were examined by mucin histochemistry and immunohistochemically. There were some differences in mucus and antigenic expression among the hepatic cysts examined. Epithelial cells of non-parasitic simple cysts and adult-type polycystic liver showed similar mucin-histochemical and immunohistochemical features, and were characterized by little mucin and weak immunoreactivities to several antibodies examined. Epithelial cells of hepatic hilar cysts were characterized by much mucin and moderate immunoreactivities to carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Epithelial cells of ciliated hepatic foregut cysts were characterized by much mucin and immunoreactivities to actin and tubulin which were positive in cilia. Epithelial cells of biliary cystadenoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. Epithelial cells of biliary cystadenocarcinoma were characterized by much mucin and moderate to strong immunoreactivities to cytokeratins CAM5.2 and AE1 and 3 as well as to CA 19-9, CEA, EMA and DU-PAN-2. These differences in epithelial mucus and antigenic expression among several types of hepatic cysts may reflect differences in their origin and biological characteristics. These differences may be helpful in the differential diagnosis of hepatic cysts in small biopsy specimens.     

Changes in the liver following penetration by a gastric ulcer (experimental investigation)

Changes in the liver following penetration by a gastric ulcer were studied in 130 albino rats. Ulcers were produced by Okabe's method. During penetration the capsule of the liver is destroyed and four zones can be distinguished in the tissues of the organ: necrosis, demarcation inflammation, necrobiosis, and proliferation of hepatocytes. Together with destructive processes, in the early stages repair processes developed in the parenchyma and connective-tissue structures. Active proliferation of hepatocytes and of bile ducts leads to their penetration into the granulation tissue at the base of the ulcer. After healing of the ulcer complete restoration of the affected areas of the liver takes place but adhesions with the stomach remain.Central Research Institute of Gastroenterology, Main Board for Health Care, Moscow City Executive Committee, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR A. I. Strukov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 370–372, March, 1980.     

肝门静脉肝内分支的形态观测及临床意义

目的 测量肝门静脉入肝后的左干、右干的有关数据，为临床肝脏疾病导管介入治疗等应用提供形态学资料。方法 取无肝病死亡后的人体肝脏标本，用游标卡尺和三角尺等进行有关数据的测量。结果 肝门静脉左干横部的长度为23～33mm；横部的根部外径为6．2～10．8mm；左干矢状部外径为6．5～9．9mm；左干外上叶支外径为3．3．6．5mm。肝门静脉右支主干长度为15～25．8mm；根部的外径为8．4～12．0mm；右后叶支外径为5．0～9．4mm；右前叶支外径为4．6～9．2mm。结论 有关形态学测量数据在肝脏疾病的导管介入性治疗和诊断应用中具有一定的参考价值。     

What is congenital hepatic fibrosis?

The hypothesis presented in this paper suggests that, at birth, the basic lesion of congenital hepatic fibrosis corresponds to ductal plate malformation of interlobular bile ducts, resulting from faulty development, i.e. disturbance in epithelio-mesenchymal inductive interactions. The immature bile ducts are subject to a progressive destructive cholangiopathy, resulting in a pattern of more or less advanced fetal type of biliary fibrosis. The destructive cholangiopathy may be of variable speed and duration in different patients. The renal lesions in autosomal recessive polycystic kidney disease, which is most often associated with congenital hepatic fibrosis, show a comparable pattern and evolution. The hypothesis that congenital hepatic fibrosis corresponds to a fetal type of biliary fibrosis would explain a number of disparate observations. According to this concept, congenital hepatic fibrosis does not correspond to a single clinical entity but to a broad, merging spectrum of conditions. All have in common that they represent some stage of biliary fibrosis, usually of the fetal type, rarely of the adult type, resulting from a slowly progressive, destructive cholangiopathy.     

Immunoglobulin deposits in the biliary remnants of extrahepatic biliary atresia: a study by immunoperoxidase staining in 128 infants

Bile duct remnants taken from 128 infants during surgery for extrahepatic biliary atresia were paraffin embedded prior to immunoperoxidase staining. Immunoglobulin deposits were found in 44 remnants. They were made up of IgM alone in 25 cases and of IgM and IgG in 19. Deposits were observed along the basement membranes of glandular structures. These findings suggest that extrahepatic bilary atresia might be an acquired and evolving disease.     

Liver stem cells: when the going gets tough they get going

The ability of the liver to regenerate is widely acknowledged, and this is usually accomplished by the entry of normally proliferatively quiescent hepatocytes into the cell cycle. However, when hepatocyte regeneration is impaired, small bile ducts proliferate and invade into the adjacent hepatocyte parenchyma. In humans and experimental animals these ductal cells are referred to as oval cells, and their association with defective regeneration has led to the belief that they are the progeny of facultative stem cells. Oval cells are of great biological interest since they may represent a target population for hepatic carcinogens, and they may also be useful vehicles for ex vivo gene therapy for the correction of inborn errors of metabolism.
The ability of oval cells to differentiate into hepatocytes has been demonstrated unequivocally. However, this process only occurs when the regenerative capacity of hepatocytes is overwhelmed, and thus, unlike the intestinal epithelium, the liver is not behaving as a classical continually renewing stem cell-fed lineage.     

结肠炎诱发肝脏屏障功能障碍的研究进展

肝脏屏障是肝脏抵御外源性有害物质侵袭的主要结构,在维持肝脏分泌功能,调控胆汁转运及细胞间信息传递中发挥重要作用。内毒素、炎性因子及胆汁酸等诱发肝脏屏障蛋白改变及屏障功能障碍,可能参与结肠炎性肝病发生。探究结肠炎对肝脏屏障的影响及机制,从肝脏屏障角度阐释结肠炎性肝病的发生机制有望为其防治提供线索和依据。     

The role of E. coli infection in the pathogenesis of primary biliary cirrhosis

Among various infectious agents possibly involved in the pathogenesis of primary biliary cirrhosis (PBC), Escherichia Coli (E. coli) has received special attention because of epidemiological and experimental evidence linking this bacterium with the disease's development. This review discusses early and more recent epidemiological studies associating recurrent urinary tract infections with E. coli and the development of PBC. We also critically review data provided over the years demonstrating disease-specific humoral and cellular immune responses against E. coli antigens in patients with PBC. Finally, we assess the relevance of experimental findings reporting cross-reactive immunity between mimicking sequences of E. coli and the major PBC mitochondrial antigens in the pathogenesis of the PBC. We also address the extent to which molecular mimicry and immunological cross-reactivity can be considered as a critical pathogenic process linking infection with self destruction.