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)

Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin's disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.
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PMID:Intrahepatic cholestatic syndromes: pathogenesis, clinical features and management. 1043 57

We describe a series of cases of extreme hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver after an allogeneic bone marrow transplant. All of the patients presented with a total cholesterol in excess of 1000 mg/dl (25.9 mmol/l). At the time they were also noted to have pseudohyponatremia. Cholesterol appeared to be predominantly carried by lipoprotein X. Intrahepatic cholestasis leading to reflux of bile lipoproteins into the bloodstream and subsequent formation of protein X appears to be the mechanism underlying this phenomenon. Complications, including retinal cholesterol thromboembolism and cholesteroloma of the lung have been seen in the patient with the highest cholesterol levels. Severe hypercholesterolemia is an important, and likely more common than previously reported, long-term complication of allogeneic hematopoietic stem cell transplantation. It is important for clinicians to familiarize themselves with the diagnostic and therapeutic challenges this condition presents.
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PMID:Severe hypercholesterolemia mediated by lipoprotein X in patients with chronic graft-versus-host disease of the liver. 1553 4

Intrahepatic cholestasis has been recognized as one of the characteristic features of the hepatic manifestations in graft-versus-host disease (GVHD). Tight junctions (TJs) play crucial roles in bile formation and alterations of TJs in hepatocytes and/or biliary epithelial cells (BECs) that cause intrahepatic cholestasis. To assess the changes of TJs in hepatocytes and BECs in a rat model of GVHD, we examined the localization of TJ-associated proteins, 7H6 and zonula occludens (ZO)-1. GVHD was induced by injecting spleen cells of parental strain rats (Brown Norway) into non-irradiated (Brown Norway x Lewis) F1 hybrid rats. Untreated F1 hybrid rats served as controls. Double-labeled immunofluorescent staining for 7H6 and ZO-1 was performed in liver sections. In control rats, immunostaining for 7H6 and ZO-1 colocalized to the apical site of BECs and was continuous along the bile canaliculi. In GVHD, 7H6 expression was decreased in BECs and was discontinuous along the bile canaliculi. On the other hand, the intensity of ZO-1 staining in hepatocytes increased and did not change in BECs compared with that of control rats. Changes in TJ-associated proteins of both hepatocytes and BECs may reflect the immunopathogenesis of GVHD-associated intrahepatic cholestasis.
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PMID:Cholestasis in a rat model of graft-versus-host disease is accompanied by alteration of the expression and distribution of tight-junction-associated proteins. 1570 33