Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestatic liver disease is primarily caused by impaired bile production on the level of hepatocytes and cholangiocytes. Clinically cholestasis can be divided into intrahepatic and extrahepatic forms based on the presence or absence of dilated bile ducts (sonography). Intrahepatic cholestasis is most frequently caused by end stage liver cirrhosis followed by primary cholangiopathies and canalicular transport defects in hepatocytes. The causes of the most important cholangiopathies, such as Primary Biliary Cirrhosis (PBC) and Primary Sclerosing Cholangitis (PSC) are so far not known. Therefore, drug therapy of cholestatic liver disease focuses on the improvement of symptoms such as fatigue, pruritus, abdominal discomfort, jaundice, xanthoma, hypercholesterolemia, portal hypertension, blood count abnormalities, osteoporosis/osteomalacia, and the prevention of complications such as bile-duct strictures in PSC and development of cholangiocarcinoma. The first choice drug in the treatment of cholestatic liver disease of various causes is urosodeoxycholic acid (UDCA), that has been shown to decrease bile acid toxicity in general and prolong the transplant free survival of patients with PBC. If cholestasis persists cirrhosis of the liver is the major complication and liver transplantation may be the definitive treatment in advanced cases of cholestatic liver disease.
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PMID:[Cholestatic liver diseases]. 945 66

Central fatigue commonly occurs in patients with primary biliary cirrhosis (PBC) and correlates closely with depression, and cholestatic rats exhibit central fatigue. Therefore, we undertook a series of experiments in both rats with cholestasis caused by bile duct resection (BDR) and sham-resected controls (15 days after surgery) to determine if experimental cholestasis is associated with symptoms of depression that can be modeled in rats, namely anhedonia (loss of pleasure) and the loss of social interest. BDR rats exhibited significant anhedonia compared with sham controls as indicated by a loss in their preference for consuming a saccharin solution, a highly desirable drink for rats. Furthermore, social interest was examined by determining the time BDR or sham rats spent investigating a juvenile rat in an open-field apparatus compared with the time spent on nonsocial behaviors. BDR rats exhibited significantly reduced time spent in social investigation and significantly more time in nonsocial behaviors than did sham rats. Major depression in humans is often associated with elevated circulating glucocorticoid levels and impaired glucocorticoid feedback. Therefore, we measured these parameters in BDR and sham rats and found a striking elevation in circulating glucocorticoid levels in BDR compared with sham animals. However, elevated circulating glucocorticoid levels in BDR rats suppressed normally in response to exogenous dexamethasone, indicating intact glucocorticoid feedback control at the pituitary level in BDR rats. In summary, we have identified behaviors in cholestatic rats that are consistent with those seen in depression.
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PMID:Chronic cholestasis in rats induces anhedonia and a loss of social interest. 965 89

Liver transplantation is a highly effective treatment for patients with advanced primary biliary cirrhosis and primary sclerosing cholangitis. Transplantation is indicated when the patient's survival with transplantation is better than without or, earlier than this, if the patient's quality of life is intolerable from intractable fatigue or pruritus. Medical therapies for chronic cholestatic liver diseases are very limited. Ursodeoxycholic acid therapy in primary biliary cirrhosis reduces cholestasis and prolongs transplant-free survival; no other drugs are of proven efficacy in primary biliary cirrhosis, and none have any benefit on the disease progression of primary sclerosing cholangitis. Aggressive endoscopic therapy may produce symptomatic and biochemical improvement in primary sclerosing cholangitis but should be done without the expectation of retarding disease progression. Bilirubin is one of five criteria of the Child-Turcotte-Pugh score, which is necessary for the United Network for Organ Sharing listing for orthotopic liver transplantation. In addition, it is a major prognostic indicator in all the predictive models for primary biliary cirrhosis. Bilirubin reduction with ursodeoxycholic acid therapy in primary biliary cirrhosis appears to parallel disease severity, and prognostic models utilizing bilirubin retain their predictive power for survival even in treated patients. In summary, medical therapies for chronic cholestatic liver disease have very little effect on disease progression and, subsequently, on the timing or selection for transplantation. Liver transplantation is the only definitive therapy for primary biliary cirrhosis and primary sclerosing cholangitis.
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PMID:Liver transplantation for primary biliary cirrhosis and primary sclerosing cholangitis: does medical treatment alter timing and selection? 974 89

The pathogenesis of the pruritus that complicates cholestasis in patients with primary biliary cirrhosis (PBC) is uncertain. The limited and inconsistent efficacy of conventional empiric therapies, such as anion exchange resins and rifampicin, has led to inconclusive trials of invasive experimental therapies, such as plasmapheresis, charcoal haemoperfusion and partial external diversion of bile. However, some double-blind, placebo-controlled trials that used a subjective primary efficacy end-point (the perception of pruritus) have suggested that certain drugs that affect the metabolism of many compounds, for example rifampicin, may be efficacious. The potential mechanisms by which such drugs may mediate a beneficial effect have not been determined. There is a paucity of data to indicate whether peripheral events, such as the accumulation of bile acids in interstitial fluid of the skin, initiate the neural events which mediate this form of pruritus. Recent findings suggest that central events in the brain, specifically an increase in neurotransmission/ neuromodulation mediated by endogenous opioid agonists (increased opioidergic tone), may be implicated. This hypothesis is supported by three lines of evidence. (1) Opioid receptor ligands with agonist properties (e.g. morphine) mediate pruritus. (2) Endogenous opioid-mediated neurotransmission/neuromodulation in the central nervous system (CNS) is increased in cholestasis. (3) Controlled trials have shown that opiate antagonists induce ameliorations of the behavioural consequence of the pruritus of cholestasis (scratching activity). In such trials, measurements of scratching activity independent of limb movements constituted an objective quantitative primary efficacy end-point. Potent opiate antagonists, that are bioavailable when given by mouth, such as nalmefene and naltrexone, may have a place in the long-term management of pruritus in patients with PBC. Evidence that increased serotoninergic neurotransmission also contributes to the pruritus is at present less strong than that implicating an involvement of the opioid system, and further investigation is needed to determine whether specific serotonin receptor subtype ligands have a place in the treatment of pruritus in patients with PBC. There is some evidence which suggests that increased serotoninergic neurotransmission in the CNS contributes to fatigue of central origin, but whether there is a causal relationship between altered serotoninergic neurotransmission and the profound fatigue that occurs in many patients with PBC is currently uncertain.
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PMID:The pathogenesis and treatment of pruritus and fatigue in patients with PBC. 1041 33

Primary biliary cirrhosis (PBC) is a serious and life-threatening illness that mainly affects women. Epidemiological data on the prevalence of the illness are unclear. The experience of women with this chronic illness has not been explored within nursing research. A review of the literature concerning PBC therefore is based on general themes relating to chronic illness. A chronic illness has two meanings: the symbolic significance and the consequences for the individual. The symbolic significance of PBC can be related to symbolism relating to the liver in general and to the general assumption that liver disease is related to alcohol consumption. The consequences for the individual woman with PBC have been described as following a disease management trajectory. This may include appreciating the major symptoms of the illness. The main symptoms of PBC are fatigue and pruritus. These are both insidious and debilitating symptoms of unclear aetiology that can cause women with PBC problems when seeking an illness explanation. The symptoms may also interfere with the woman's body image and her caring role. It is suggested that the factors that relate to PBC may result in social isolation for women with the illness.
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PMID:The experience of women with primary biliary cirrhosis: a literature review. 1045 54

The diagnosis of primary biliary cirrhosis (PBC) is most often made in the asymptomatic phase, sometimes before the development of abnormal liver biochemistry. The antimitochondrial antibody remains the predominant hallmark, although not all patients test positive, even when the most sensitive techniques are used. The etiology of PBC remains elusive; studies suggest that the interlobular bile duct destruction is immune based, and associated autoimmune diseases are common. There are no surrogate markers that predict outcome in asymptomatic patients, whose chance of survival is less than that of age- and sex-matched populations but much better than the median survival of eight years in patients with symptomatic PBC. Symptoms common in this disease are fatigue, pruritus and xanthelasma, as well as complications of portal hypertension and osteoporosis. Treatment includes symptomatic and preventive measures, as well as specific therapeutic measures. Immunosuppressive therapy has yielded disappointing results in the long term management of PBC, and the only therapy shown to improve survival is the hydrophobic dihydroxy bile acid ursodeoxycholic acid. Treatment at a dose of 13 to 15 mg/kg/day is optimal, given in separate doses or as a single dose at least 4 h from giving the oral anion exchange resin cholestyramine, which may be used to control pruritus. However, liver transplantation remains the only cure for this disease, and the best postoperative survival is seen in patients whose serum bilirubin does not exceed 180 micromol/L at the time of liver transplantation. Recurrence takes place but is rarely symptomatic and does not deter from the benefits of transplantation.
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PMID:Update on primary biliary cirrhosis. 1065 26

Primary biliary cirrhosis (PBC) is a chronic autoimmune disease characterised by cholestatic liver function tests, antimitochondrial antibodies, and abnormal liver histology. Early descriptions of a rare rapidly progressive disease no longer reflect the more indolent progress often seen today. Many patients have significant long term morbidity through symptoms such as fatigue and itch with a minority progressing to liver failure and need for transplantation. The current data on the diagnosis, clinical progression, and treatment of PBC are reviewed.
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PMID:Primary biliary cirrhosis: new perspectives in diagnosis and treatment. 1072 61

Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver, which predominantly affects women once over the age of 20 years. Most cases are diagnosed when asymptomatic (60%). The antimitochondrial antibody is present in serum in most, but not in all, patients with PBC. The disease generally progresses slowly but survival is less than an age- and gender-matched general population. The symptomatic patient may have fatigue, generalized pruritus, portal hypertension, osteoporosis, skin xanthomata, fat soluble vitamin deficiencies, and/or recurrent asymptomatic urinary tract infections. Many nonhepatic autoimmune diseases are found in association with PBC and may prompt initial presentation. To date, immunosuppressive therapy has not been shown to prolong survival in PBC. The hydrophilic bile acid, ursodeoxycholic acid (UDCA), has been shown when given in a dose of 13 to 15 mg/kg daily for up to 4 years to delay the time to liver transplantation or death. This therapy also causes a significant improvement of all the biochemical markers of cholestasis but has no beneficial effects on any of the symptoms or associated disorders. Treatment with UDCA does not obviate the need for liver transplantation. Therapies to prevent complications arising from malabsorption, portal hypertension, and/or osteoporosis are required as well. Good control of pruritus can be achieved in most patients. PBC is diagnosed with increasing frequency, but the agent(s) responsible for this slowly progressive destruction of the interlobular bile ducts remains elusive and hence a specific therapy remains unavailable.
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PMID:Management of primary biliary cirrhosis. The American Association for the Study of Liver Diseases practice guidelines. 1073 59

Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterised by the destruction of small intrahepatic bile ducts. Although known for many years its etiology and pathogenesis still remains uncertain. Alterations of humoral and cellular immune functions suggests an autoimmune pathogenesis. Primary biliary cirrhosis typically affects middle-aged women who reports fatigue and itching. Diagnosis is usually based on abnormal biochemical tests of liver function, presence of antimitochodrial antibodies (especially anti-M2) and histologic evaluation of liver biopsy specimens. Relatively small number of diagnosed cases in Poland may be due to insufficient knowledge on this disease in our country.
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PMID:[Primary biliary cirrhosis]. 1096 8

Pruritus is experienced by about 80% of patients with primary biliary cirrhosis. It can have a marked negative impact on the quality of life of patients, and it can be an indication for liver transplantation. There is evidence to suggest that the pruritus of cholestasis is mediated, at least in part, by endogenous opioids. A central component has been proposed. Behavioural data have shed light on the pathogenesis of this form of pruritus. Fatigue affects the majority of patients with primary biliary cirrhosis. It interferes with work performance and family life. An idea is emerging that suggests that fatigue in primary biliary cirrhosis also may be mediated centrally. Research tools need to be developed to study fatigue objectively in patients with primary biliary cirrhosis.
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PMID:Pruritus and fatigue in primary biliary cirrhosis. 1097 20


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