Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reviews cholestatic liver diseases which are characterized by disappearance of the intrahepatic bile ducts ("vanishing bile duct" diseases). In neonates and children, the most important entities are extrahepatic bile duct atresia and paucity of intrahepatic bile ducts, including syndromatic and nonsyndromatic varieties. Immunological mechanisms play a role in the bile duct obstruction observed in primary biliary cirrhosis, graft-versus-host disease and chronic liver transplant rejection, and possibly also in primary sclerosing cholangitis and sarcoidosis with chronic intrahepatic cholestasis. Idiopathic adulthood ductopenia represents a newly defined entity, the nature of which remains unclear. Mention is made of recently reported forms of intrahepatic bile duct destruction due to toxins and drugs (iatrogenic cholangiopathies). New insight into the pathogenesis of these diseases has been brought about by progress in immunology, imaging techniques of the liver and hepatobiliary surgery.
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PMID:Destructive intrahepatic bile duct diseases. 225 46

Diseases with disappearing intrahepatic bile ducts may be developmental, immunological, infective, vascular, or chemical in origin. The immunological group includes primary biliary cirrhosis, graft-versus-host disease, and sarcoidosis. HLA class 2 antigens are displayed on the bileducts and recognition of biliary antigens by cytotoxic T-cells leads to destruction of interlobular ducts. Primary sclerosing cholangitis is associated with immunological features, but the hepatic histology is not that of immunological duct disease. The association with immunodeficiency syndromes, and the finding that secondary sclerosing cholangitis may occur in patients with the acquired immunodeficiency syndrome who are infected with cytomegalovirus, suggest that primary sclerosing cholangitis might be infective in origin. In bacterial cholangitis there is contiguity between the biliary system and the intestinal tract and usually, but not necessarily, partial biliary obstruction. Interference with the hepatic arterial supply to the bileducts leads to vascular cholangitis. Chemical cholangitis follows injection of scolicidal agents into the biliary tree. Diseases with disappearing bileducts have a long natural history and hepatocellular failure occurs late. In the late stages hepatic transplantation gives good results.
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PMID:The syndrome of disappearing intrahepatic bile ducts. 288 86

Bile duct cells (BDCs), especially intrahepatic cholangiocytes, are primary targets of immune-related injury in such pathologic processes as liver graft rejection, liver graft-versus-host disease, and primary sclerosing cholangitis. Cholestasis and progressive loss of intrahepatic BDCs indicate chronicity in these diseases. The present investigation characterizes the acquisition of immune markers of intrahepatic BDCs isolated from mice after bile duct ligation. Purified BDCs from cholestatic C57BL/6 (H-2b) mice express not only the major histocompatibility complex (MHC) class I and class II antigens but also the costimulatory molecules B7-1 (CD80) and B7-2 (CD86). The expression of the MHC class II molecules on BDCs before and after interferon (IFN)-gamma exposure is also demonstrated by immunohistochemistry on the cultured cells. Cytotoxicity assays indicate the vulnerability of these cells as targets for immunologic injuries. Effector cells generated from B10.BR splenocytes (H-2k) against C57BL/6 splenocytes (H-2b) show comparable killing of BDCs and EL4 cells, the latter being a lymphoma line that was established from the C57BL/6N (H-2b) mouse. An immortalized mouse BDC line (IBDC) is included in this study to validate some of the findings from BDCs isolated from bile duct-ligated mice. We suggest that cholestatic BDCs express surface antigens different from those of normal epithelial cells that result in increased susceptibility to damage by immune mechanisms.
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PMID:Phenotypical and functional characterization of intrahepatic bile duct cells from common duct ligated mice. 896 Jun 34

Ursodeoxycholic acid is a dihydroxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established. Newer indications include its use in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft-versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis.
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PMID:Ursodeoxycholic acid in the treatment of liver diseases. 912 1

Experimental graft-versus-host disease (GVHD) across minor histocompatibility antigens was developed by injecting spleen and bone marrow cells (9:1) of congenic B10.D2 mice into sublethally irradiated BALB/c mice, and the histologic features of the liver were studied for up to 14 months after transplantation. Both intrahepatic and extrahepatic bile ducts were severely involved in the GVHD process and showed features of non-suppurative cholangitis. Inflammatory cells, mainly lymphocytes, abutted the bile ducts and infiltrated into the duct epithelial layer together with a variety of degenerative changes in the epithelial cells. The peak inflammatory activity occurred about 2-3 weeks after transplantation. Thereafter, the inflammatory cell infiltration around the bile ducts and in the bile duct epithelial layer gradually became reduced in severity, although the infiltration persisted during the entire 14 month observation period. Periductal and duct wall fibroplasia began about 1 week after transplantation and gradually progressed. After 2-3 months post-transplantation, distinct ductal and periductal fibrosis of both intrahepatic and extrahepatic bile ducts was observed. This histologic feature resembled that of primary sclerosing cholangitis (PSC). These results suggest that PSC lesions might develop as a result of chronic cellular immunologic mechanisms in GVHD across minor histocompatibility barriers.
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PMID:Diffuse biliary tract involvement mimicking primary sclerosing cholangitis in an experimental model of chronic graft-versus-host disease in mice. 970 53

This manuscript reviews and summarizes the histopathology of the liver in the various "vanishing bile duct diseases". These represent conditions associated with progressive disappearance of intrahepatic bile duct branches. Congenital diseases of this nature comprise so-called extrahepatic bile duct atresia and paucity of interlobular bile ducts (syndromic and non-syndromic). In the adult, vanishig bile duct diseases are represented amongst others, by primary biliary cirrhosis, primary sclerosing cholangitis, idiopathic adulthood ductopenia, liver allograft rejection, graft-versus-host disease and drug-induced and toxic cholangitis.
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PMID:Histopathology of vanishing bile duct diseases. 1035 36

Many hepatobiliary diseases can result in cholestasis. The main causes of chronic cholestasis in adults are primary biliary cirrhosis, which is characterized by portal triad inflammation and segmental necrosis of interlobular bile ducts, and primary sclerosing cholangitis, in which the intra and/or extrahepatic bile ducts undergo inflammation and fibrosis. The diagnosis is based on the presence of evidence of cholestasis and of symptoms specific for each condition. A number of drugs, sarcoidosis, total parenteral nutrition, chronic liver transplant rejection, and graft-versus-host disease can also cause chronic cholestasis. The treatment of these conditions has benefited greatly from rational use of ursodeoxycholic acid.
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PMID:[Chronic cholestatic disorders in the adult]. 1060 78

Ursodeoxycholic acid is currently the only established drug for the treatment of chronic cholestatic liver diseases. It has cytoprotective, anti-apoptotic, membrane stabilizing, anti-oxidative and immunomodulatory effects. Prolonged administration of ursodeoxycholic acid in patients with primary biliary cirrhosis (PBC) is associated with survival benefit and a delaying of liver transplantation. There is evidence that it might even prevent progression of the histologic stage of PBC. It also has a beneficial effect on primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, liver disease associated with cystic fibrosis, chronic graft versus host disease, total parenteral nutrition associated cholestasis and various pediatric cholestatic liver diseases. In the present review the current knowledge about the mechanisms of the action and role of ursodeoxycholic acid in the treatment of various liver diseases has been discussed.
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PMID:Use of ursodeoxycholic acid in liver diseases. 1120 13

1. Recurrent primary biliary cirrhosis (PBC) after transplantation is controversial, but most studies support disease recurrence within the graft. 2. Granulomatous destructive cholangitis should be present, and exclusion of acute and chronic rejection, graft-versus-host disease, biliary obstruction, viral hepatitis, and drug effects is mandatory before making a diagnosis of recurrent PBC. 3. Recurrent primary sclerosing cholangitis (PSC) after transplantation is difficult to diagnose because of the lack of a diagnostic gold standard. 4. Well-defined cholangiographic and histological criteria should be present, and exclusion of preservation injury, blood group type incompatibility between donor and recipient, chronic rejection, hepatic arterial occlusion, and viral infection is mandatory before making a diagnosis of recurrent PSC. 5. Most studies support recurrent autoimmune hepatitis (AIH) after transplantation based on clinical, biochemical, serological, and histological criteria. Exclusion of rejection, viral infection, drug effects, and biliary obstruction is mandatory before making a diagnosis of recurrent AIH. 6. Intermediate-term patient and graft survival are excellent for patients with recurrent autoimmune liver diseases within the transplanted liver, but additional studies are required to address the impact of disease recurrence on long-term patient and graft survival.
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PMID:Recurrent primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis after transplantation. 1168 82

Ursodeoxycholic acid (UDCA), the 7beta-epimer of chenodeoxycholic acid, has multiple hepatoprotective activities. UDCA modifies the bile acid pool, decreasing levels of endogenous, hydrophobic bile acids while increasing the proportion of nontoxic hydrophilic bile acids. UDCA has a choleretic effect, increasing hepatocellular bile acid excretion, as well as cytoprotective, antiapoptotic, and immunomodulatory properties. UDCA has been shown to delay development of gastroesophageal varices and progression to cirrhosis as well as to improve long-term survival in patients with primary biliary cirrhosis. Significant improvement of abnormal liver tests may be achieved during UDCA therapy in patients with primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis-associated liver disease, nonalcoholic fatty liver disease, graft-versus-host disease of the liver, total parenteral nutrition-induced cholestasis, and in some pediatric cholestatic liver diseases. However, unlike the effects of UDCA in primary biliary cirrhosis, the long-term effects of UDCA in disease progression and survival in these other conditions remain to be established.
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PMID:Use of ursodeoxycholic acid in patients with liver disease. 1182 40


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