Damaged Bile Ducts Research Articles

Immunohistochemical analysis of adhesion molecules in the micro-environment of portal tracts in relation to aberrant expression of PDC-E2 and HLA-DR on the bile ducts in primary biliary cirrhosis.

We have examined immunohistochemically the expression of adhesion molecules in the micro-environment of portal tracts and their relationship to the expression of the pyruvate dehydrogenase E2 complex (PDC-E2) and HLA-DR in liver biopsy specimens. Ten cases of primary biliary cirrhosis (PBC) and 19 controls were examined, including four cases of extrahepatic biliary obstruction, six of chronic viral hepatitis, and nine normal livers. In PBC, the damaged small bile ducts demonstrated an increased expression of PDC-E2 and an aberrant expression of HLA-DR; about half of these damaged bile ducts also expressed intercellular adhesion molecules (ICAM)-1 and a few expressed vascular adhesion molecule (VCAM)-1. In addition, lymphocyte function-associated antigen (LFA)-1 and very late antigen (VLA)-4 were expressed on infiltrating lymphocytes around these bile ducts. In contrast, in control livers, these alterations in antigen expression on the bile ducts were either not observed or were only focal and weak, when present. These findings suggest that ICAM-1/LFA-1 and also VCAM-1/VLA-4 linkages between the damaged bile ducts and lymphocytes may facilitate antigen-specific reactions such as the presentation of antigens, possibly PDC-E2, to the periductal lymphocytes in PBC. ICAM-1, VCAM-1, and E-selectin were strongly expressed on the endothelial cells of some vessels in the portal tracts in PBC, suggesting the facilitation of the recruitment of lymphocytes around the bile ducts of PBC. VCAM-1, a member of the immunoglobulin superfamily, has not hitherto been reported on bile ducts.

Apoptosis of bile duct epithelial cells in hepatic allograft rejection

Liver biopsy remains the 'gold standard' for monitoring rejection in liver transplant patients. Portal inflammation, bile duct damage and endothelialitis are recognized features of hepatic allograft rejection. The pathogenesis of the bile duct injury during rejection, however, remains unclear. To define the mechanism of bile duct damage, we studied the light- and electronmicroscopic appearance of hepatic tissue from selected patients in whom allograft failure was solely due to rejection. Of the 25 orthotopic liver transplant rejection cases examined, 17 were mild, seven were moderate and one was severe rejection. Light microscopy examination of the damaged bile duct epithelium revealed evidence of apoptosis which was confirmed by electronmicroscopy. Furthermore, there appeared to be a positive correlation between the grade of rejection and the number of apoptotic cells. Also included in the study were 13 cases of chronic active hepatitis and 10 normal livers which showed the least apoptotic cells. We conclude that the identification of apoptotic cells in damaged bile ducts in allograft biopsies might be helpful in the diagnosis of rejection and in assessment of the severity of rejection.

Eosinophilic infiltration of the liver in primary biliary cirrhosis: A morphological study

Eosinophils and their secretory proteins are important in necroinflammatory processes. In this study we surveyed eosinophilic infiltration of the liver in 176 liver biopsy specimens from patients with primary biliary cirrhosis. A considerable number of eosinophils were found in the portal tracts in 51 of these specimens (29%), whereas this finding occurred in only 2 of 50 (4%) specimens from patients with viral chronic active hepatitis. Eosinophilic infiltration of the portal tracts was focal. These eosinophils were immunohistochemically shown to contain the secreted form of eosinophilic cationic protein. Grades of eosinophilic infiltration of the portal tracts were higher in those livers with higher grades of lymphoplasmacytic infiltration, granulomas and florid duct lesion in the portal tracts, and they were lower in those livers with higher grades of bile duct disappearance and orcein-positive granuoles in hepatocytes. In the livers of patients with primary biliary cirrhosis, eosinophils were abundant around the damaged bile ducts, around the portal vein branches and at the marginal regions, and they were scattered in the portal tracts, whereas only the last pattern was seen in viral chronic active hepatitis. Peripheral blood eosinophils tended to be increased in primary biliary cirrhosis patients with higher grades of eosinophilic infiltration of the portal tracts. Eosinophilic infiltration of the portal tracts may play a role in immunological injuries of the interlobular bile ducts in primary biliary cirrhosis. (HEPATOLOGY 1993;17:206–212.)

Eosinophilic infiltration of the liver in primary biliary cirrhosis: A morphological study

Eosinophils and their secretory proteins are important in necroinflammatory processes. In this study we surveyed eosinophilic infiltration of the liver in 176 liver biopsy specimens from patients with primary biliary cirrhosis. A considerable number of eosinophils were found in the portal tracts in 51 of these specimens (29%), whereas this finding occurred in only 2 of 50 (4%) specimens from patients with viral chronic active hepatitis. Eosinophilic infiltration of the portal tracts was focal. These eosinophils were immunohistochemically shown to contain the secreted form of eosinophilic cationic protein. Grades of eosinophilic infiltration of the portal tracts were higher in those livers with higher grades of lymphoplasmacytic infiltration, granulomas and florid duct lesion in the portal tracts, and they were lower in those livers with higher grades of bile duct disappearance and orcein-positive granuoles in hepatocytes. In the livers of patients with primary biliary cirrhosis, eosinophils were abundant around the damaged bile ducts, around the portal vein branches and at the marginal regions, and they were scattered in the portal tracts, whereas only the last pattern was seen in viral chronic active hepatitis. Peripheral blood eosinophils tended to be increased in primary biliary cirrhosis patients with higher grades of eosinophilic infiltration of the portal tracts. Eosinophilic infiltration of the portal tracts may play a role in immunological injuries of the interlobular bile ducts in primary biliary cirrhosis.

Expression of HLA-DR antigens on interlobular bile ducts in primary biliary cirrhosis and other hepatobiliary diseases: An immunohistochemical study

Using a monoclonal antibody to α chains of HLA-DR antigens, we found that damaged biliary epithelial cells in primary biliary cirrhosis (PBC) and, to a lesser degree and frequency, in other hepatobiliary diseases expressed HLA-DR antigens, while normal bile ducts did not. There was no correlation between biliary epithelial expression of HLA-DR antigens and intraepithelial migration of HLA-DR-positive cells. In PBC, HLA-DR antigens were strongly expressed on the damaged bile ducts surrounded by no or mild inflammatory cell infiltration (nonflorid duct lesion) and on those surrounded by intense lymphoid cells (florid duct lesion). Immunoelectron microscopy confirmed the presence of HLA-DR antigens on the cellular membranes of damaged biliary epithelial cells. Although expression of HLA-DR antigens on bile ducts may itself be a nonspecific epiphenomenon of damaged bile ducts, it seems possible in PBC that biliary epithelial cells are at first damaged in some way and express HLA-DR antigens (and probably self-antigens), and then fall victim to an autoimmune reaction characterized by marked lymphoid cell infiltration (florid duct lesions). The agent causing nonflorid duct lesions is unknown. The reasons why such expression does not lead to immunologic reactions in other hepatobiliary diseases are only speculative.

Clinicopathological Significance of Granulomas

Primary biliary cirrhosis (PBC) is histologically characterized by chronic non-suppurative destructive cholangitis (CNSDC), and is also a granulomatous disease. The characteristics of granulomas and the correlation between granulomas and bile duct changes were morphologically investigated in 31 patients with granulomas, compared with in those without granulomas.Results were as follows : 1) Most of the granulomas (93%) were poorly-defined, and well-organized granulomas with distinct fibrosis were rare (7 %).2) Granulomas with multinucleated giant cells (MGCs) were not always well-organized and were found both in portal area and near central veins. MGCs sometimes had inclusions with negative H-E stain.3) Seventy-two per cent of granulomas were found in portal area, some of them were in contact with damaged bile ducts, others surrounded them.4) The patients with granulomas were rather early in the histologic stages. Twenty-three of 31 patients with granulomas were asymptomatic.5) Ratio of disappearance of interlobular bile ducts was significantly lower in PBC patients with granulomas than in those without granulomas.From these results, it was suggested that granulomas in PBC were closely related to interlobular bile duct lesions and that something derived from interlobular bile ducts seemed to play an important role for granuloma formation.

Expression of beta 2-microglobulin on interlobular bile ducts in primary biliary cirrhosis and other hepatobiliary diseases.

Expression of beta 2-microglobulin, a reliable marker of HLA Class I, on the interlobular bile ducts (bile ducts) was surveyed using an immunoperoxidase method in paraffin sections of specimens from patients with a variety of hepatobiliary diseases. Normal bile ducts showed negativity or weak cytoplasmic positivity in normal as well as diseased livers. On the other hand, abnormal bile ducts showing degenerative or proliferative changes in primary biliary cirrhosis and graft-versus-host disease revealed enhanced expression of this protein, suggesting that these damaged bile ducts might be more susceptible to T cell-mediated immune attack in these immunologic diseases. However, enhanced expression of this protein was also similarly found on abnormal bile ducts in several nonimmunologic biliary diseases including extrahepatic biliary obstruction. Enhanced expression of this protein on the interlobular bile ducts may therefore be an epiphenomenon secondary to different primary pathologic events in the biliary tree, such as immunologic and nonimmunologic processes.

Human amnion as a bioprosthesis for bile duct reconstruction in the pig

Despite technical advances in management, the complication of late stricture formation and biliary sepsis still occur in bile duct reconstruction. In an attempt to avoid bilioenteric anastomosis, which bypasses the biliary sphincter mechanism, various biologic and artificial materials have been employed clinically and experimentally to replace the damaged bile duct. No satisfactory biliary replacement material has yet been found. In the experimental model of bile duct stricture that has been presented, human amnion bile duct injuries mimicking those seen in clinical practice were repaired using human amnion as a free graft. Noncircumferential duct loss appeared to be satisfactorily repaired using amnion, and the amnion repair was found to be as good as or superior to plastic repair; however, circumferential duct loss was not adequately repaired with the amnion graft.

In situ characterization of the cell-surface antigens of the mononuclear cell infiltrate and bile duct epithelium in primary biliary cirrhosis

To analyze the tissue distribution of mononuclear cells and HLA antigens in primary biliary cirrhosis, we studied liver biopsies of 12 patients at different stages of the disease, using the avidin-biotin-peroxidase technique and monoclonal antibodies directed against T and B lymphocytes, T-cell subsets, macrophages, NK/K cells, dendritic cells, and HLA class I and II antigens. To evaluate the proportion of activated T cells we used anti-interleukin-2-receptor antibodies and a double-staining technique for T cells and class II HLA antigens. In all biopsies activated T cells predominated in the portal areas and around the damaged bile ducts. T4 cells almost always outnumbered T8 cells. While B cells, NK/K cells, and dendritic cells were always scarce, macrophages constituted about 30% of the cellular infiltrate. Biliary epithelium, which normally expresses HLA class I antigens, displayed mainly HLA class II antigens. The predominance of T4 cells around the bile ducts, which express class II antigens, suggests that class II-restricted T4 lymphocytes may mediate liver damage in primary biliary cirrhosis.

Effect of toluene exposure on the liver under different experimental conditions

The effect of exposure to toluene inhalation was studied in adult mice, rats, and rabbits, and, further, in rats of different age groups and rats subjected to partial hepatectomy or ligation of the common bile duct. It was found that (1) toluene has no substantial liver damaging effect on the mouse, rat, or rabbit; (2) induction of microsomal monooxygenase enzymes by toluene is almost completely independent of physiological changes affecting the functional-anatomical state of the liver (aging), of restriction of the functional capacity of the organ (partial hepatectomy), and of irreversible hepatic damage (bile duct ligation); (3) toluene does not in any way interfere with surgically induced hepatic damage. The consequences of surgical interventions, in turn, just like the age-dependent changes, do not modify the minimal ultrastructural damaging effect of toluene.

Slow infusion cholangiography in jaundice. An experimental study in the dog

56 intravenous cholangiograms were performed in eleven dogs with either advanced hepatic damage or complete common bile duct obstruction. If radiographic visualization of the biliary system did not occur within 8 hours after a 30 minute infusion with 0.6 ml/kg iodipamide 52%, the result could not be improved by just extending the infusion time to 2 and 6 hours. However, a slight improvement was obtained, when the iodipamide dose was increased up to 1.8 ml/kg. Nevertheless we do not recommend a massive increase of the dose in the icteric patient, because it is likely that the risk of toxic side effects increases with an increasing iodipamide dose.

Analysis of Causes and Treatment of Biliary Leakage after Hepatobiliary Surgery

Hepatobiliary surgery is very common, and its operation is mainly based on the principle of human anatomy to carry out operations. In the actual operation, if there are no corresponding protective measures, it is easy to damage bile tract and bile duct, even biliary leakage complications will be caused after the surgery, and a certain effect will have on the patient's body and mind. It is necessary to strengthen the prevention and treatment of biliary leakage on the basis of thinking on the causes of bile leakage, and it can reduce the chance of the complications. Therefore, this article mainly focuses on strengthening the analysis and discussion on the cause of biliary leakage after hepatobiliary surgery and the treatment of related aspects.

The Damaged Bile Duct

The Damaged Bile Duct