Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gallstones are common and their incidence increases with age. Fifty per cent of these stones are in the common bile duct (CBD) in the elderly. Most of them are silent but with time there is an increasing chance of developing symptoms which are more likely to be serious in the elderly. Failure to relieve mechanical obstruction of bile flow may lead to secondary biliary cirrhosis. It has been estimated that on average secondary biliary cirrhosis develops some seven years after the onset of obstruction from a stricture, four and half years after gallstone obstruction and 10 months after the onset of malignant stricture. The characteristic features are the pathological findings of portal-portal linkages, with a pattern of monolobular cirrhosis and the preservation of normal vascular relationships. Secondary biliary cirrhosis may lead to hepatic insufficiency and portal hypertension with the resultant complications, such as bleeding oesophageal varices, hypersplenism with pancytopenia, ascites and encephalopathy. We describe a patient in whom the diagnosis was not suspected until laparotomy and confirmed only at autopsy.
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PMID:Gallstone cirrhosis: are we only seeing the tip of the iceberg? 834 47

Secondary biliary cirrhosis in the rat is an attractive model since unlike other models it does not rely on exogenous toxic compounds to induce cirrhosis. However, because little is known about the microcirculatory abnormalities of this model, this study investigated hemodynamics in rats with predefined functional impairment and related them to different aspects of stereologically quantified structure. All animals with at least 50% reduction in microsomal function, assessed by the aminopyrine breath test, had portal hypertension. The sinusoidal space, as assessed by multiple indicator dilution in the perfused liver, was reduced whereas large vessel space was increased. This reduction in sinusoidal space could contribute to increased portal resistance. The degree of intrahepatic shunting varied as assessed by a microsphere technique (13.9 vs. 0.5% in controls). These alterations were confirmed by stereological analysis. Numerically, there was excellent agreement between functional indicator dilution data and anatomic quantitation. Microvascular exchange was impaired as in other models of cirrhosis as shown by a reduced extravascular albumin space (4.5 vs. 2.2%, p < 0.01). In contrast to alterations in vascular space, this functional impairment was not reflected in the stereologically assessed space of Disse which averaged 5% of liver volume in both groups. Finally, in spite of reduced microsomal function in vivo (aminopyrine breath test) and in vitro (aminopyrine N-demethylase activity), the smooth endoplasmic reticulum was maintained (4.3 vs. 3.5 m2/ml cytosol, n.s.), which demonstrates that microsomal function in this model is reduced per unit hepatocyte. This suggests that the sick-cell hypothesis applies to secondary biliary cirrhosis in the rat.
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PMID:Structure-function relationship in secondary biliary cirrhosis in the rat. Stereologic and hemodynamic characterization of a model. 844 30

The characterization of mice models of portal hypertension (PHT) is lacking in the literature. Therefore, the aim of the present study was to make a histological approach during development of PHT in two models of cirrhosis with PHT compared with one model of isolated PHT. The model of isolated PHT was developed by partial portal vein ligation (PPVL). Two portal hypertensive cirrhotic mice models were developed either by common bile duct ligation (CBDL) or administration of carbon tetrachloride (CCl(4)) subcutaneously (twice weekly, 1 ml/kg). These models represent, respectively, a secondary biliary cirrhosis and alcoholic cirrhosis. Mice were killed at several time points to evaluate liver changes by histological and ultrastructural methods. A correlation was made with portal pressure measurements. Histology revealed the absence of fibrosis or cirrhosis in PPVL mice. They developed an isolated portal hypertension. After CBDL induction, the mice developed the characteristics of cirrhosis after 6 weeks, with simultaneous increase in portal pressures. Fifty percent of the mice had ascites at that time point. Sixteen weeks after administration of CCl(4), a micronodular cirrhotic aspect of the liver was seen associated with signs of portal hypertension. This is the first descriptive study of three widely used animal models in mice, allowing the study of pathophysiological changes in cirrhosis and portal hypertension. The PPVL in mice leads to a model of isolated portal hypertension. Secondary biliary cirrhosis developed after 6 weeks of common bile duct ligation in 50% of the mice that developed ascites. Subcutaneous injection of CCl(4) for 16 weeks induces cirrhosis and portal hypertension, without ascites. Moreover, the present study is the first description of a cirrhotic model in mice developed by subcutaneous injections of CCl(4). Well-described mice models will facilitate use of knock-out or transgenic mice and lead to a better understanding of the underlying molecular pathways in the field of portal hypertension and cirrhosis.
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PMID:Comparison of three research models of portal hypertension in mice: macroscopic, histological and portal pressure evaluation. 1871 70

This study was aimed to investigate the molecular mechanisms underlying prevention of hepatic fibrosis by S-nitroso-N-acetylcysteine (SNAC), a nitric oxide donor that inhibits lipid peroxidation. Secondary biliary cirrhosis was induced by 4 weeks of common bile duct ligation (CBDL). Both sham-operated and CBDL animals received SNAC (6.0 micromol/kg/day) starting 2 weeks after surgery. SNAC treatment reduced the increase in blood enzyme activities (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), induced by CBDL. Histological changes were attenuated and there was a significant decrease in the area of liver fibrosis and in the activation of stellate cells measured by alpha-smooth muscle actin (alpha-SMA) immunostaining. The increase in TBARS concentration and hydroperoxide-induced chemiluminescence were also reduced by SNAC treatment. SNAC down-regulated expression of collagen 1 alpha, alpha-SMA, tumor necrosis factor-alpha, tumor growth factor-beta, metalloproteinase-2, metalloproteinase inhibitor 1, platelet-derived growth factor (PDGF), and PDGF receptor in CBDL rats. These effects were accompanied by inhibited activation of extracellular signal-regulated kinases, Jun amino-terminal kinases, p38 and Akt. Antifibrotic effects were more efficient than those of the free thiol NAC administered at a dose of 60 mumol/kg. In conclusion, results obtained indicate that SNAC, beyond its antioxidant capacity, exerts antifibrotic effects in rats with secondary biliary cirrhosis by down-regulating increased expression of genes and modulating intracellular signaling pathways that contribute to the accumulation of matrix proteins. Thus, SNAC may be an interesting candidate for the treatment of human fibrosis and cirrhosis.
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PMID:S-nitroso-N-acetylcysteine attenuates liver fibrosis in cirrhotic rats. 2006 61

Late complications arising after bile duct injury (BDI) include biliary strictures, hepatic atrophy, cholangitis and intra-hepatic lithiasis. Later, fibrosis or even secondary biliary cirrhosis and portal hypertension can develop, enhanced by prolonged biliary obstruction associated with recurrent cholangitis. Secondary biliary cirrhosis resulting in associated hepatic failure or digestive tract bleeding due to portal hypertension is a substantial risk factor for morbidity and mortality after bile duct repair. Parameters that determine the management of late complications of BDI include the type of biliary injury, associated vascular injury, hepatic atrophy, the presence of intra-hepatic strictures or lithiasis, repetitive infectious complications, the quality of underlying parenchyma (fibrosis, secondary biliary cirrhosis) and the presence of portal hypertension. Endoscopic drainage is indicated for patients with uncontrolled acute sepsis, patients at high operative risk, patients with cirrhosis who are not eligible for liver transplantation and patients who have previously undergone several attempts at repair. Roux-en-Y hepaticojejunostomy, whether de novo or as an iterative repair, is the technique of reference for post-cholecystectomy BDI. Hepatic resection is indicated in only rare instances, mainly in case of extended hilar stricture, multiple stone retention in one sector of the liver or in patients for whom the repair is deemed technically difficult. Liver transplantation is indicated only in exceptional circumstances, when secondary biliary cirrhosis is associated with liver failure and portal hypertension.
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PMID:Long-term consequences of bile duct injury after cholecystectomy. 2495 66