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

Cholestasis may be extrahepatic or intrahepatic in origin. The block in bile secretion may be complete or incomplete to variable extent. Complete cholestasis occurs in case of primary parenchymal disease (intrahepatic cholestasis) or total obstruction of extrahepatic bile ducts (extrahepatic cholestasis). Incomplete block in bile secretion is due to incomplete obstruction of intra- or extrahepatic bile ducts (intra- or extrahepatic cholestasis or both). Histologically, it is useful to distinguish between bilirubionstasis and cholate-stasis. Complete secretory block causes as early changers: bilirubinostasis (in hepatocytes, canaliculi and Kupffer cells) in acinar zone 3, and "ductular reaction" in acinar zone 1. The latter refers to an increase in periportal ductular profiles, associated with neutrophil infiltration. With longer duration of cholestasis, further lesions ensue: feathery degeneration of hepatocytes due to retention of detergent bile acids, cholestatic liver cell rosettes representing a shift from hepatocellular to biliary differentiation, xanthomatous cells reflecting hyperlipidemia, cholate stasis in acinar zone 1 due to overload of membrane-damaging bile acids, eventually paraportal bile infarcts, and progressive ductular reaction. The latter may be due to multiplication of pre-existing ductules, to metaplasia of periportal hepatocytes, or to activation of progenitor cells. It is invariably associated with periductular fibrosis: the pacemaker for increasing matrix deposition, resulting in biliary fibrosis and eventually in true biliary cirrhosis. Incomplete cholestasis (e.g. PBC, PSC) is characterized by absence of bilirubinostasis during long periods of time, whereas the afore mentioned features of chronic cholestasis do appear. Hence follows that the most reliable markers of chronic incomplete cholestasis are cholate stasis, cholestatic rosettes and ductular reaction. Bilirubinostasis is only a late and often ominous sign.
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PMID:Histopathology of cholestasis. 860 Jun 86

Sympathetic nervous system activation has been documented in several cardiovascular disorders. In some, characterized by cardiac failure and portal hypertension accompanying hepatic cirrhosis, the sympathetic nervous stimulation is reflex and, to some extent, compensatory but has adverse consequences. For example, in cardiac failure, the sympathetic nerves of the heart are preferentially stimulated, providing adrenergic support to the failing myocardium but at the probable cost of arrhythmogenesis and progressive myocardial deterioration. The sympathetic activation present in patients with essential hypertension, which involves the sympathetic outflows to skeletal muscle, heart, and kidneys and is seen particularly in younger patients, differs from these examples in that the sympathetic nervous stimulation is apparently not reflex and the primary cause is unknown. There is, however, evidence that activation of forebrain pressor noradrenergic nuclei may be of importance as an underlying central nervous system mechanism. This sympathetic nervous stimulation in patients with essential hypertension, in addition to initiating the blood pressure elevation, may also contribute to the commonly associated metabolic abnormalities of insulin resistance and hyperlipidemia, with neural vasoconstriction having metabolic consequences, impairing glucose delivery and causing insulin resistance in muscle, and retarding postprandial clearing of lipids in liver. Trophic effects of sympathetic activation on cardiovascular growth are claimed but have yet to be demonstrated conclusively in humans.
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PMID:Sympathetic nervous system: contribution to human hypertension and related cardiovascular diseases. 864 1

Liver disease is accompanied by major qualitative and quantitative disturbances in plasma lipoprotein metabolism, the extent and intensity of which depend on the degree of parenchymal damage, cholestasis, or both. The main objective of this study was to determine the cholesteryl ester transfer CETP activity and its association with the lipoprotein neutral lipid composition in patients with either liver cirrhosis or cholestasis, as compared to normal controls. Lipoproteins were isolated by ultracentrifugation, lipids and apolipoproteins were measured by conventional methods, and the fatty acid composition was established by gas chromatography; CETP activity in lipoprotein-deficient plasma was measured by determining the transfer of [3H]cholesteryl esters from HDL to VLDL. Lipoprotein lipase and hepatic lipase activities were measured in post-heparin plasma by radiochemical methods. In patients with liver cirrhosis, low levels of VLDL, HDL, apo B, and Lp(a) were observed, as well as a change in the composition of HDL particles, with increases in the relative proportion of triglyceride and free cholesterol. Respectively, the last two changes could be attributed in part to the low hepatic lipase activity observed in this study, and to the low lecithin:cholesterol acyltransferase activity previously observed by others. In patients with cholestasis, a moderate hyperlipidemia due to the elevation of LDL was found. In contrast, HDL and apo A-I levels were very low reflecting a low number of HDL particles, which also had altered compositions with increases in the triglyceride and free cholesterol contents relative to apo A-I and esterified cholesterol, respectively. As regards the fatty acid composition of lipoprotein lipids, the two groups of patients showed, in general, a lower proportion of linoleic acid and a compensating higher proportion of oleic acid as compared to the controls, changes that were observed in both cholesteryl esters and triglycerides. In contrast, the proportions of oleic and palmitoleic acids in phospholipids were increased, whereas that of stearic acid was decreased in patients as compared to controls. In patients with liver cirrhosis, as well as in controls, no changes were observed in the fatty acid compositions of cholesteryl ester, triglycerides, or phospholipids among the different lipoproteins, which probably reflects the equilibration reached by the action of CETP. In patients with cholestasis, no differences were observed in fatty acid composition among the lipoprotein phospholipids but, interestingly, cholesteryl esters from VLDL had a significantly lower linoleic acid content than those from HDL, whereas triglycerides from VLDL had significantly higher oleic acid and lower linoleic acid contents than those from HDL. This distinct fatty acid composition of the neutral lipids between lipoproteins was associated with a significant decrease (25%) in the cholesteryl ester transfer activity in patients with cholestasis. We suggest that fat malabsorption due to the biliary defect may induce a decrease in cholesteryl ester transfer protein synthesis or section, which in turn would slow the equilibration of the neutral lipids among plasma lipoproteins.
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PMID:Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids. 874 May 80

The objective of this study was to evaluate the association of intrahepatic cholestasis, pulmonary stenosis, and hyperlipemia with osseous and renal abnormalities in Alagille's syndrome. A total of 37 patients (25 males and 12 females) with ages ranging between 8 months and 27 years were included. Clinical records as well as radiological and ultrasonographic studies were reviewed. Chronic cholestasis was observed in all patients. Thirteen had favorable clinical outcome and normal hepatic sonograms. Clinical and sonographic evidence of portal hypertension was found in 13 patients and of cirrhosis in 8 patients. The remaining 3 patients required hepatic transplantation due to severe cholestasis. Hyperlipemia correlated with hepatic malfunction. Pulmonary stenosis and renal hypoplasia were the most frequently associated abnormalities. All patients showed a peculiar facies. Abnormal "butterfly" vertebrae were present in 18 patients and ulnar or phalangeal shortening in 11 patients. Ultrasonography allowed hepatobiliary disease assessment and helped to establish indications for hepatic transplantation. Renal and osseous abnormalities were not specific but in the appropriate clinical setting reinforced the diagnosis.
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PMID:Syndrome of Alagille: radiological and sonographic findings. A review of 37 cases. 900 Apr 11

Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non-progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non-progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.
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PMID:Review: nonalcoholic steatohepatitis. 919 88

Chronic administration of a soybean-derived polyenylphosphatidylcholine (PPC) extract prevents the development of cirrhosis in alcohol-fed baboons. To assess whether this phospholipid also affects earlier changes induced by alcohol consumption (such as fatty liver and hyperlipemia), 28 male rat littermates were pair-fed liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 21 d, and killed 90 min after intragastric administration of the corresponding diets. Half of the rats were given PPC (3 g/l), whereas the other half received the same amount of linoleate (as safflower oil) and choline (as bitartrate salt). PPC did not affect diet or alcohol consumption [15.4 +/- 0.5 G/(kg.d)], but the ethanol-induced hepatomegaly and the hepatic accumulation of lipids (principally triglycerides and cholesterol esters) and proteins were about half those in rats not given PPC. The ethanol-induced postprandial hyperlipemia was lower with PPC than without, despite an enhanced fat absorption and no difference in the level of plasma free fatty acids. The attenuation of fatty liver and hyperlipemia was associated with correction of the ethanol-induced inhibition of mitochondrial oxidation of palmitoyl-1-carnitine and the depression of cytochrome oxidase activity, as well as the increases in activity of serum glutamate dehydrogenase and aminotransferases. Thus, PPC attenuates early manifestations of alcohol toxicity, at least in part, by improving mitochondrial injury. These beneficial effects of PPC at the initial stages of alcoholic liver injury may prevent or delay the progression to more advanced forms of alcoholic liver disease.
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PMID:Polyenylphosphatidylcholine attenuates alcohol-induced fatty liver and hyperlipemia in rats. 927 63

Nonalcoholic steatohepatitis (NASH) is the term used for a common form of fatty liver presenting in adults with varied clinical manifestations. The most common presentation is asymptomatic elevation of liver enzymes (AST or SGOT and ALT or SGPT), which can be discovered incidentally in the course of an annual checkup, life insurance examination, or as part of surrogate screening before blood donation. At the other end of the clinical spectrum is the patient with complications from cryptogenic cirrhosis, who also shows a lack of evidence of alcohol as an etiological factor in pathogenesis. Clinical associations of probable relevance include gender (female), obesity, diabetes, and hyperlipidemia, but many patients do not conform to any of these stereotypes (e.g., young men of normal weight with normal fasting glucose and lipid levels). Liver biopsy confirms the diagnosis of NASH, the association of steatosis with an inflammatory response being the sine qua non for the condition and "creeping fibrosis" being a variable but possibly sinister feature. Newer imaging techniques may provide convincing evidence of steatosis, but they give little insight into ongoing fibrosis, and liver biopsy therefore remains the gold standard. The mainstay of treatment remains judicious weight loss coupled with positive dietary advice, including the ingestion of adequate but not excessive vitamins. After initial encouraging data. the assessment of ursodeoxycholic acid currently being studied under randomized controlled conditions is eagerly awaited.
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PMID:Nonalcoholic fatty liver (NASH syndrome). 943 7

Chronic pancreatitis (CP), a disease described only in 1946 by Comfort and colleagues is currently a global disease. Chronic alcoholism, albeit is the most frequent etiologic factor for the disease in most of the affluent nations, a form of CP of undetermined etiology, tropical calculous pancreatitis (nutritional pancreatitis, Afro-Asian pancreatitis, or tropical calculous pancreatopathy) has been recognized to be prevalent in many developing nations. Hereditary pancreatitis inherited as an autosomal dominant disease is reported from all parts of the world. A landmark is the recent discovery of a gene that transmits the disease. Nearly 10% of cases of CP are truly "idiopathic" with no identifiable cause. Recent studies indicate that the idiopathic variety of CP has two subsets--a juvenile form and a senile or late onset form, with distinct clinical features. It is extremely rare to see CP secondary to hyperlipidemia or hypercalcemia. These etiologic associations appear to be overemphasized. Epidemiological studies indicate that alcoholism is growing in incidence all over the world along with an increase in all alcohol-associated disorders such as cirrhosis of the liver or pancreatitis. A genetic predisposition to alcoholic pancreatitis is suspected based on population studies, but not proven. The influence of cigarette smoking in enhancing alcohol-induced injury to the pancreas underscores the health hazard associated with alcoholism and cigarette smoking--two habits that often coexist in many individuals. The recent finding that all forms of CP are premalignant further emphasizes the need to enforce preventive measures. The hope is that CP is a preventable disease. The despair is that alcoholism is increasing and spreads across geographic and religious boundaries.
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PMID:Chronic pancreatitis: a historical and clinical sketch of the pancreas and pancreatitis. 953 Nov 14

Liver transplantation is now routinely used as a definitive treatment for patients with advanced cirrhosis. As survival after transplantation in most centers is at or above 70% to 80% at 1 year, an increasing number of liver transplant recipients requires further medical care. Several medical complications may develop during the immediate or long-term postoperative periods, including renal dysfunction, arterial hypertension, neurological complications, and psychiatric complications. In addition, other metabolic complications often develop in a more insidious manner, such as obesity, hyperlipidemia, diabetes mellitus, and posttransplant bone disease. Because the liver allograft function is frequently normal in many recipients experiencing the above-mentioned complications, the gastroenterologist, internist, or family practitioner frequently has a role in the diagnosis and management of these complications. In this review, we discuss the basic pathophysiological concepts and suggest guidelines for the diagnosis and management of frequent medical problems encountered after liver transplantation.
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PMID:Common medical diseases after liver transplantation. 970 Aug 42

1. There is accumulating evidence for a range of abnormalities in the nitric oxide (NO) signalling cascade in human cardiovascular disorders. 2. In the present review we assess the literature detailing such evidence in early (hyperlipidaemia) and end-stage (heart failure) disease, with emphasis on the mechanisms by which the disturbances are thought to occur. 3. Strategies for the correction of disturbed NO signalling in these states are reviewed and include both prescribed pharmacological interventions, such as lipid-lowering therapy and novel uses of angiotensin-converting enzyme inhibitors, as well as non-pharmacological interventions, such as exercise and dietary supplementation with L-arginine and n-3 polyunsaturated fatty acids. 4. In addition to a decreased production/function of NO, the possible detrimental effects of a chronic elevation in NO production in patients with liver cirrhosis, together with a novel use of antibiotics to correct this perturbation, is outlined.
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PMID:Restoration of nitric oxide function in human hyperlipidaemia, congestive heart failure and liver cirrhosis. 975 Sep 51


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