Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease whose aetiopathogenesis is unknown. PSC is frequently associated with inflammatory bowel disease, in particular chronic ulcerative colitis, is most commonly observed in young males and is clinically characterized by fatigue, pruritus and jaundice. The diagnosis is supported by a cholestatic biochemical profile and histological abnormalities, and confirmed by visualization of an abnormal biliary tree. The natural history of the disease is currently being evaluated but is generally recognized to be slowly progressive, leading to complications of chronic cholestasis, portal hypertension and biliary cirrhosis. There is no specific medical treatment, and orthotopic liver transplantation remains the only definitive treatment for patients with end-stage PSC. A more rational approach to medical therapy will ensue upon a better understanding of the aetiopathogenesis of this disease.
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PMID:Sclerosing cholangitis. 951 10

Progressive familial intrahepatic cholestasis (PFIC), also known as Byler disease, is an inherited cholestasis of hepatocellular origin which is characterized by cholestasis presenting often in the neonatal period leading to death due to liver failure at ages ranging from infancy to adolescence. The pattern of appearance of affected children within families is consistent with autosomal recessive inheritance. The etiology is poorly understood but several studies have recently provided support for an heterogeneity with at least three subcategories among the spectrum of PFIC. The first subtype is characterized by an early onset, often during the neonatal period, a severe pruritus, normal serum gamma-glutamyltransferase (GGT) activity and cholesterol level, high concentration of serum primary bile acids, absence or very low levels of primary bile acids, absence or very low levels of primary bile acids in bile, and absence of ductular proliferation on standard optical liver histology. Its leads to death due to liver failure within a few years, rarely after adolescence. It is possibly due to an inborn error in primary bile acid secretion and recently, a locus for this subtype has been mapped in the original Byler pedigree to 18q21-q22, the benign recurrent intrahepatic cholestasis region. In the second subtype, affected children exhibit also normal serum GGT activity and cholesterol level and absence of ductular proliferation, but have no pruritus and only traces of primary bile acids in serum. An inborn error in primary bile acid synthesis has been demonstrated in this subtype. The third subtype presents later in life, carries a higher risk of portal hypertension and gastrointestinal bleeding and ends in liver failure at a later age. It is characterized by a mild and unconstant pruritus, high GGT serum activity, moderately raised concentrations of serum primary bile acids, normal concentration of biliary primary bile acids, and ductular proliferation and inflammatory infiltrate with patency of intra and extrahepatic bile ducts. An abnormal expression of the MDR3 gene is involved. A fair proportion of children affected with all subtypes of PFIC may benefit from oral bile acid therapy. In some cases partial external biliary diversion or liver transplantation should be proposed.
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PMID:[Progressive familial intrahepatic cholestasis and hereditary anomalies lf hepatocellular metabolism of bile acids]. 1022 12

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 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

Most of the care of liver disease in alpha(1)-antitrypsin (alpha(1)-AT) deficiency involves supportive management for complications of chronic liver disease including gastrointestinal bleeding, ascites, edema, encephalopathy, coagulation disturbances, spontaneous bacterial peritonitis, and hepatorenal syndrome. Some of these patients will have manifestations of cholestatic injury, including pruritus, hypercholesterolemia, and steatorrhea with fat-soluble vitamin deficiencies. The major challenge for the clinician taking care of these patients is the timing of referral for liver transplantation therapy. Timing of such referral is a relatively straightforward decision in alpha(1)-AT-deficient patients with progressive liver dysfunction. Some patients have nonprogressive or slowly progressing liver disease even after the development of cirrhosis or portal hypertension. Timing of liver transplantation in these patients should not be based simply on the presence of cirrhosis, portal hypertension or mild liver synthetic dysfunction, but rather on the basis of a subjective judgment by the hepatologist, patient, and family that manifestations of liver disease are interfering with overall life functioning.
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PMID:Alpha(1)-Antitrypsin Deficiency. 1109 5

The treatment of children with end-stage liver disease involves the coordinated management of nutritional deficiencies, ascites, pruritus, encephalopathy, and portal hypertension. The implementation of management strategies depends upon a parent or guardian to administer the plan in the context of a child at different stages of developmental, physiologic, emotional, and physical maturity. Fat-soluble vitamins (A, D, E, and K) and micronutrient levels should be monitored routinely and supplemented if deficient. In some patients, supplemental nutrition to provide additional energy and protein is needed to ensure optimal growth and development. Ascites often respond to spironolactone and sodium restriction, but may require the addition of a loop diuretic or even abdominal paracentesis. Pruritus significantly impairs the quality of life of patients and is typically treated with ursodeoxycholic acid, rifampin, or an antihistamine. Partial biliary diversion, or liver transplant in some instances, is necessary for patients with self-mutilating pruritus that results from intrahepatic cholestasis. Hepatic encephalopathy is poorly defined in infants and small children. Elevated serum ammonia serves as a surrogate marker for encephalopathy, which is treated with dietary protein restriction and lactulose. The usefulness of medical prophylaxis for esophageal varices has been noted in adults, though such studies have not been performed in children. If variceal bleeding becomes problematic, treatment with endoscopic variceal banding or sclerotherapy is indicated. A surgical shunt to reduce portal pressure is needed in some cases. Orthotopic liver transplant ultimately may be necessary to overcome the unrelenting consequences of end-stage liver disease.
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PMID:End-stage Liver Disease in Children. 1156 Jul 88

Cholestatic liver disease affects a small percentage of children, but therapy results in millions of healthcare dollars being spent each year. Close monitoring of nutritional status, pruritus, and complications from portal hypertension should improve the patient's quality of life and survival without liver transplantation. Other comorbid conditions, such as cardiac or renal disease, must also be integrated into the care plan and will affect the overall prognosis of the patient. Portal hypertension leads to ascites, variceal hemorrhage, and infection, which can result in significant mortality if not promptly recognized and treated. Surgical shunts are being used less because the expertise to perform endoscopic sclerotherapy and endoscopic band ligation is available at most medical centers. However, many cholestatic diseases, including biliary atresia, progressive familial intrahepatic cholestasis (PFIC) I, II, and III, and Alagille syndrome, may still require liver transplantation (Table 1). The cost of this procedure can exceed several hundred thousand dollars per patient, without including the annual costs of immunosuppressant therapy and medical monitoring. Meticulous medical management of nutrition and the sequelae of portal hypertension may prolong survival and reduce the potential morbidity and mortality of liver transplantation.
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PMID:Treatment of Pediatric Cholestatic Liver Disease. 1295 47

When cholestatic liver disease is present, liver ultrasound should be performed to ascertain if cholestasis is extrahepatic or intrahepatic. If bile ducts appear dilated and the probability of interventional treatment is high, endoscopic retrograde cholagio-pancreatography (ERCP) or trans-hepatic cholangiography (THC) should be the next step. If the probability of interventional therapeutics is low, cholangio-MRI should be performed. Once bile duct dilation and space occupying lesions are excluded, a work up for intrahepatic cholestasis should be started. Some specific clinical situations may be helpful in the diagnostic strategy. If cholestasis occurs in the elderly, drug-induced cholestatic disease should be suspected, whereas if it occurs in young people with risk factors, cholestatic viral hepatitis is the most likely diagnosis. During the first trimester of pregnancy cholestasis may occur in hyperemesis gravidorum, and in the third trimester of gestation cholestasis of pregnancy should be suspected. A familial history of recurrent cholestasis points to benign recurrent intrahepatic cholestasis. The occurrence of intrahepatic cholestasis in a middle-aged woman is a frequent presentation of primary biliary cirrhosis, whereas primary sclerosing cholangitis should be suspected in young males with inflammatory bowel disease. The presence of vascular spider nevi, ascites, and a history of alcohol abuse should point to alcoholic hepatitis. Neonatal cholestasis syndromes include CMV, toxoplasma and rubinfections or metabolic defects such as cystic fibrosis, alpha1-antitrypsin deficiency, bile acid synthesis defects, or biliary atresia. The treatment of cholestasis should include a management of complications such as pruritus, osteopenia and correction of fat soluble vitamin deficiencies. When hepatocellular failure or portal hypertension-related complications occur, liver transplantation should be considered.
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PMID:Diagnostic and therapeutic approach to cholestatic liver disease. 1497 98

To test new treatment modalities, a pilot study with a novel noninvasive biophysical methodology (Delta-S DVD) that can artificially exert a "decrease of entropy" through the patented electromagnetic-driven delivery of "energy clusters" was designed. This process has been modulated and integrated by the body as a "self" source to support the energy-dependent functional stores, thus modifying reparative into regenerative mechanisms of liver parenchyma. Seven long-standing hepatitis C virus-positive (Child A-B) cirrhosis patients with overt symptoms and portal hypertension and failure or side effects of antiviral drug treatment underwent 40-min sessions of Delta-S DVD daily for six months and were followed up monthly. At the end of the first month, rapid improvement of symptoms and a decrease of portal hypertension were noted. At the end of treatment, all patients showed either a complete (80%) or a partial (20%) regression of fatigue (FISK score), peripheral edema, pruritus, and palmar erythema. As observed, despite having stopped beta-blockers, F1 esophageal varices disappeared (60%), whereas F2 decreased to F1. The Doppler ultrasound aspect of partial (40%) or total (20%) atrophy was either reduced (60%) or reverted to normal (20%), and the respiratory dynamics of the portal vein improved (80%) or normalized (20%), whereas gross scarring nodules disappeared in 40% of cases. These promising data pave the way for an innovative physiopathological approach with extensive clinical applications.
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PMID:Cirrhosis progression as a model of accelerated senescence: affecting the biological aging clock by a breakthrough biophysical methodology. 1524 89

Liver transplantation is the treatment of choice for end stage liver disease and not a treatment specifically for portal hypertension. A patient with complications of portal hypertension must be evaluated for the presence, etiology, and severity of liver disease to determine the most appropriate therapy. In a Child's Class A patient, who would not be a liver transplant candidate for two to three years, surgical shunts may be indicated. Shunt surgery, however, does not address the underlying liver disease. Liver transplantation is reserved for the patient with complications of cirrhosis (such as ascites, encephalopathy, malnutrition, intractable pruritus, and variceal hemorrhage) for whom no other form of therapy exists.
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PMID:The role of liver transplantation in the management of portal hypertension. 1556 72


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