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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcoidosis often involves the liver with mild elevation of serum enzymes and granulomas histologically. Rarely, chronic cholestasis, portal hypertension, cirrhosis, or nodular hyperplasia may be found. The pathogenesis of the portal hypertension and of the cirrhosis are not understood, in part because large samples of tissue have seldom been described. We describe the clinical and anatomic findings of four patients with sarcoid liver disease in whom the whole livers were available for examination. One patient had cirrhosis, one had diffuse nodular hyperplasia, and two had small regions of parenchymal fibrosis. The first two of these had a history of variceal bleeding and healed portal vein thrombosis. One had chronic cholestasis without cirrhosis. We suggest that the cirrhosis and focal fibrosis were caused by ischemia secondary to primary granulomatous phlebitis of portal and hepatic veins. The portal hypertension in two patients was likely secondary to portal vein thrombosis, because cirrhosis was absent at the onset of variceal bleeding.
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PMID:The role of granulomatous phlebitis and thrombosis in the pathogenesis of cirrhosis and portal hypertension in sarcoidosis. 930 82

We studied, retrospectively, 92 children who were first seen with neonatal cholestasis and who were followed up until liver test results normalized. Among the 92 children, 81 displayed factors responsible for chronic and/or acute perinatal distress. Onset of jaundice was recorded at a mean age of 7 days, and mean duration was 3.5 months. Stools, initially discolored in 39 children, were normally colored at a mean age of 1.7 months. Hepatomegaly present in 90 children resolved at a mean age of 13 months. Liver test results were normal at the age of 1 year in 83 children and normalized at a mean age of 10 months. Liver histologic examination, performed in 70 children, showed moderate portal and lobular fibrosis, multinucleated giant hepatocytes, and hematopoietic foci; findings in follow-up liver biopsy specimens from 15 children were normal or improved. Spontaneously resolving forms of neonatal cholestasis may result from the association of several factors, including immaturity of bile secretion and perinatal disease leading to hepatic hypoxia or ischemia.
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PMID:Transient neonatal cholestasis: origin and outcome. 1035 58

Parenchymal microabscesses (MA) in liver transplant biopsies are frequently associated with cytomegalovirus (CMV) infection. However, other potential causes of MA have not been fully investigated. We studied additional etiologies for MA via histological evaluation and clinicopathological correlation. Three hundred seventy-two liver transplant biopsies from 97 patients (from 1991 to 1997) were reviewed and stained immunohistochemically for CMV. Numerous histological features were evaluated including size and number of MA, lobular and portal inflammation, and cholestasis. Medical records were reviewed for radiographic, laboratory, and other clinical data from the time of biopsy. The chi2 or Fisher's Exact test and ANOVA with adjusted multiple comparisons were used to determine statistical significance. Sixty-two of 372 biopsies (17%) from 43 patients contained MA. Biopsies were obtained between 4 days and 2.3 years posttransplant (median, 14 days). Nineteen percent of biopsies had CMV infection at the time of biopsy; 27% were associated with other bacterial, viral, or fungal infections; 10% had graft ischemia; 15% had biliary obstruction/cholangitis; 3% had a combination of ischemia and sepsis; and no explanation was found in 26% of biopsies. Numerous MA within a biopsy (>9) correlated with CMV infection (P <.005); no other histological features, including size of MA, correlated with the etiology of MA. Overall, 43 of 97 (44%) liver transplantation patients at our institution had biopsies demonstrating MA at some point in their posttransplantation course. CMV infection appears responsible for only a minority of cases. MA, although nonspecific, are an important histological finding in numerous conditions that may have a significant impact on both graft survival and overall patient morbidity.
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PMID:The significance of microabscesses in liver transplant biopsies: a clinicopathological study. 982 17

Cell death by apoptosis is thought to be involved in various pathophysiological situations involving the liver. Indeed, an understanding of apoptosis is becoming increasingly helpful for understanding disease and for patients' care. In this article, we review current scientific and clinical concepts of apoptosis, including death factors such as Fas ligand and tumor necrosis factor, apoptotic signal transduction mechanisms, and the role of intracellular proteinases called caspases. We also discuss apoptosis in the liver, as related to ischemia/reperfusion injury, cholestasis, and cancer, circumstances which physicians often face in the field of the liver surgery.
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PMID:Apoptosis and the liver: relevance for the hepato-biliary-pancreatic surgeon. 993 90

Cholangiocytes contribute significantly to bile formation through the vectorial secretion of water and electrolytes and are a focal site of injury in a number of diseases including liver ischemia and post-transplantation liver failure. Using ischemia in intact liver and adenosine triphosphate (ATP) depletion in cultured cells to model cholangiocyte injury, these studies examined the effects of metabolic inhibition on cholangiocyte viability and structure. During 120 minutes of ischemia or ATP depletion, cell viability and tight junctional integrity in cholangiocytes were maintained. However, both the in vivo and in vitro models displayed striking alterations in the secondary structure of the plasma membrane. After 120 minutes, the basolateral (BL) interdigitations were diminished and the apical (Ap) microvilli were significantly decreased in number. The BL and Ap membrane surface areas decreased by 42 +/- 8% and 63 +/- 2%, respectively. Despite these changes, F-actin remained predominantly localized to the membrane domains. In contrast, in a time course that paralleled the loss of microvilli, the actin-membrane linking protein ezrin progressively dissociated from the cytoskeleton. These studies indicate that cholangiocyte ATP depletion induces characteristic, domain-specific changes in the plasma membrane and implicate alterations in the membrane-cytoskeletal interactions in the initiation of the changes. Pending the re-establishment of the differentiated domains, the loss of specific secondary structures may contribute to impaired vectorial bile duct secretion and postischemic cholestasis.
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PMID:Reorganization of cholangiocyte membrane domains represents an early event in rat liver ischemia. 1021 17

Hepatic blood flow decreases under cholestasis and there is evidence that NO regulates liver microvascular perfusion. Thus, the aim of the present study was to evaluate NO synthesis in cholestasis. Cholestasis was induced by bile-duct ligation (BDL) in male Wistar rats. Bilirubins and enzyme activities were measured in serum. Lipid peroxidation, GSH, GSSG and glycogen were determined in liver. Histopathological analysis was performed. Serum NO2- + NO3- concentration was measured by the Gries reaction. iNOS immunoblot analysis was carried out using an iNOS polyclonal antibody. After 7 days of BDL lipid peroxidation increased while GSH/GSSG ratio decreased. Serum NO2- + NO3- and liver iNOS protein were reduced, accompanied by ischemia as revealed by the histopathological analysis. GSH upregulates NO synthesis by increasing iNOS mRNA levels and iNOS activity, thus the reduction of GSH/GSSG ratio may be responsible for the downregulation of iNOS protein and NO synthesis, which in turn may explain the observed ischemia and the decreased hepatic blood perfusion in cholestasis reported by others.
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PMID:Nitric oxide and inducible nitric oxide synthase expression are downregulated in acute cholestasis in the rat accompanied by liver ischemia. 1124 95

Cholestasis is a common finding after liver transplantation and usually signifies graft dysfunction. The most important factor in the evaluation of patients with cholestasis is an awareness of the disorders that commonly arise along a time continuum post-transplant. Therefore, the approach to cholestasis requires a systematic review of biochemical, histological, and radiographic data. This article considers the causes of cholestasis in liver transplant recipients, excluding those associated with biliary anastomotic stricturing. These causes include conditions as diverse as ischemia reperfusion injury, ABO blood group incompatibility, hepatic arterial thrombosis, cytomegalovirus infection, fibrosing cholestatic hepatitis secondary to hepatitis B and C viruses, recurrent primary sclerosing cholangitis, recurrent primary biliary cirrhosis, and chronic rejection. Also examined are management issues pertinent to these conditions and strategies used in preventing or diminishing the effects of cholestasis once established.
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PMID:Cholestatic diseases of liver transplantation. 1135 20

The aim of this study is to analyze the impact of the recipient's disease severity on graft size requirements and outcome in adult-to-adult living donor liver transplantation. A limiting factor in adult-to-adult living donor liver transplantation has been adequacy of graft size. A minimal graft-recipient weight ratio (GRWR) of 0.8% to 1% has been suggested, without taking the recipient's disease into account. Forty adults underwent liver transplantation using left (n = 10; mean weight, 481 +/- 83 g) or right lobes (n = 30; mean weight, 845 +/- 182 g). We recorded graft survival, Child-Turcotte-Pugh score, and occurrence of small-for-size syndrome (poor bile production, prolonged postoperative prothrombin time, and cholestasis without ischemia markers). Small grafts were defined as GRWR of < or =0.85%. Large grafts were defined as GRWR greater than 0.85%. Six patients died within 6 months of transplantation (early patient survival rate, 85%); two patients died late of tumor recurrence. Among transplant recipients with normal liver function or Child's class A, there was no significant difference with the use of small (n = 6) or large (n = 9) grafts (graft survival rates, 83% v 88%, respectively; P =.65). Among patients with Child's class B or C, graft survival rates were 74% in recipients of large grafts (n = 19) and 33% in recipients of small grafts (n = 6; P =.023). Five of 6 patients with Child's class B or C who received small grafts developed small-for-size syndrome; 2 patients died (1 patient after retransplantation) and 3 patients survived (2 patients after retransplantation). Graft function and survival are influenced not only by graft size, but also by pretransplantation disease severity. GRWR as low as 0.6% can be used safely in patients without cirrhosis or in patients with Child's class A. Transplant recipients with Child's class B or C require a GRWR greater than 0.85% to avoid small-for-size syndrome and related complications.
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PMID:Critical graft size in adult-to-adult living donor liver transplantation: impact of the recipient's disease. 1169 30

Primary sclerosing cholangitis (PSC) is an idiopathic inflammatory disorder of the biliary tract characterized by diffuse biliary tract stricture formation, progressive chronic cholestasis and the development of secondary biliary cirrhosis. Biliary tract ischemia can produce morphological changes identical to PSC. We propose the existence of a localized renin-angiotensin system within the liver and extend the hypothesis that aberrant production of angiotensin II within the portal tract is the critical event contributing to the pathogenesis of PSC. A chronic reparative and proliferative state caused by chronic ischemia may promote carcinogenesis. Proof of this hypothesis will have implications for future therapeutic approaches given that current treatments for PSC aimed at reducing inflammation or the effects of cholestasis have proven ineffective.
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PMID:Aberrant local renin-angiotensin II responses in the pathogenesis of primary sclerosing cholangitis. 1278 43

BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury is characterized by features such as cholestasis. Mitochondria become susceptible to damage during ischemia and after reperfusion. The aim of this study was to determine if silymarin and tauroursodeoxycholic acid (TUDC), would prevent impairment of liver mitochondrial function following I/R injury. METHODS: Livers of male Wistar rats were subjected to 45 min of hepatic ischemia. During the 90 min of reperfusion, livers were perfused with either vehicle, silymarin, or TUDC. Changes in membrane potential, mitochondrial respiration as well as susceptibility to mitochondrial permeability transition (MPT) induction were evaluated and endogenous adenine nucleotides were measured. RESULTS: In rats subjected to I/R, compared with the control group, a severe impairment of mitochondrial bioenergetics was observed. State 3 respiration was decreased and state 4 enhanced, associated with lower membrane potential developed following succinate energization. An increased susceptibility to MPT induction by calcium/phosphate was also observed. The effects of I/R injury were ameliorated in the presence of silymarin but not TUDC. Similarly, ATP levels following I/R were lower, in comparison with the control group and the silymarin treatment but not TUDC. CONCLUSION: Thus, silymarin, but not TUDC, prevents the most significant changes that occur in mitochondria during I/R, and probably, the associated cell dysfunction, through their central role in cellular bioenergetics.
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PMID:Protection against post-ischemic mitochondrial injury in rat liver by silymarin or TUDC. 1285 Jun 94


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