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)

Greenland familial cholestasis is a severe form of intrahepatic cholestasis described among indigenous Inuit families in Greenland. Patients present with jaundice, pruritus, bleeding episodes, and steatorrhea, and die in childhood due to end-stage liver disease. We investigated the possibility that Greenland familial cholestasis is caused by a mutation in FIC1, the gene defective in patients with progressive familial intrahepatic cholestasis type 1 and many cases of benign recurrent intrahepatic cholestasis. Using single-strand conformation polymorphism analysis and sequencing of the FIC1 exons, a missense mutation, 1660 G-->A (D554N), was detected and was shown to segregate with the disease in Inuit patients from Greenland and Canada. Examination of liver specimens from 3 Inuit patients homozygous for this mutation revealed bland canalicular cholestasis and, on transmission electron microscopy, coarsely granular Byler bile, as previously described in patients with progressive familial intrahepatic cholestasis type 1. These data establish Greenland familial cholestasis as a form of progressive familial intrahepatic cholestasis type 1 and further underscore the importance of unimpeded FIC1 activity for normal bile formation.
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PMID:A missense mutation in FIC1 is associated with greenland familial cholestasis. 1109 41

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

Drug-induced liver disease can result from dosage-dependent hepatotoxicity or from adverse reactions to drugs used in therapeutic dosage. The latter idiosyncratic hepatotoxins can cause clinical syndromes that mimic all known liver diseases, so that drugs must be considered as the possible causal agent for all unexplained cases of liver disease. The only specific antidote for dosage-dependent hepatotoxicity is n-acetylcysteine (and some other sulfhydryl donors), which is highly effective for the prevention of significant hepatotoxicity after acetaminophen overdose. Early diagnosis and prompt withdrawal of the offending drug is the key to successful management of most drug-induced liver diseases. The mainstay of treatment is supportive care, with careful monitoring for signs of acute liver failure or progression to chronic liver disease. In cases of liver failure, close liaison with a liver transplant center is crucial; referral for liver transplantation should be considered if standard transplant criteria are fulfilled. Pruritus is a major symptom of drug-induced cholestasis; protracted cases may respond to ursodeoxycholic acid. Corticosteroids can be considered for cases of drug-induced hepatitis, especially those with evidence of immune hypersensitivity, if no improvement is seen in 8 to 12 weeks. Although there are no controlled trials, some patients may respond favorably.
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PMID:Drug-Induced Liver Disease. 1109 6

The treatment of patients with pruritus of liver disease poses a challenge to the clinician. Resins (cholestyramine or colestipol) in quantities of 4 to 16 grams a day should be the initial agents used. In those who remain refractory, diphenhydramine should be added, although sedation may limit the use of higher doses. If symptoms still persist, rifampin up to 600 mg/day can be added to the above regimen with close monitoring of hepatic function. If, despite this combination, pruritus persists and quality of life remains poor, experimental therapies in the form of oral opioid antagonists, and orthotopic liver transplantation should be considered.
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PMID:Pruritus. 1109 28

Benign recurrent intrahepatic cholestasis is a rare autosomal recessive disorder characterized by repeated episodes of intense pruritus and jaundice. Each attack lasts from several weeks to months before resolving spontaneously. Patients are completely asymptomatic for months to years between symptomatic periods. The disorder does not lead to progressive liver disease. Although attacks seem to be associated with a viral prodrome, an inciting viral agent or toxin has not been defined. Genetic studies have mapped the defect of this disorder to the long arm of chromosome 18 and a gene that codes for a P-type ATPase, which appears to be involved in aminophospholipid transport. Therapy during symptomatic periods is supportive and aimed at relief of severe pruritus until the episode resolves spontaneously.
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PMID:Benign recurrent intrahepatic cholestasis. 1129 Dec 37

We report here, the first pediatric living-related liver transplant in Saudi Arabia and the Middle East. Our patient is a 2 year old girl with a diagnosis of progressive familial intrahepatic cholestasis, causing intractable pruritus and failure to thrive requiring liver transplantation. The child was successfully transplanted using a segment of her mother's liver for living-related liver transplantation. Two years post-transplantation the patient is doing well. With the ongoing crises in cadaveric organ availability and the high prevalence of pediatric liver disease, living related liver transplantation is an ideal solution to this difficult and challenging problem.
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PMID:Living-related liver transplantation. 1130 18

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly affects middle-aged women; fatigue and pruritus are the most common symptoms at presentation. Liver function tests are consistent with cholestasis and reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase with or without elevation of aminotransferase levels. Histologically, PBC is characterized by the destruction of the intrahepatic small bile ducts and subsequently fibrosis. The serological hallmark of the disease is the presence of antimitochondrial antibodies, which are found in 95% of patients with PBC. The antimitochondrial antibodies are directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. PBC generally slowly progresses, even over decades, and may lead to liver failure. In symptomatic patients, advanced age, elevated serum bilirubin levels, decreased serum albumin levels, and cirrhosis each correlate with shortened survival. Immunosuppressive and anti-inflammatory drugs have been used in the treatment of PBC based on the presumed autoimmune pathogenesis, but satisfactory agents leading to complete reversal or cure of the disease are not available. At present ursodeoxycholic acid appears to be the only effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving ursodeoxycholic acid still develop progressive disease and require transplantation; transplantation is the only effective therapy at the end stage of the disease.
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PMID:Primary biliary cirrhosis: from induction to destruction. 1135 23

We describe a patient who suffered from intestinal perforation after abdominal trauma. Perioperatively, he was treated with a single dose of piperacillin and 9 doses of imipenem/cilastatin over 3 days. The patient was discharged 5 days after surgery in good clinical condition and with normal liver values except for a marginal elevation of alanine aminotransferase. Two weeks after discharge, he developed fatigue, fever and pruritus, necessitating rehospitalization. He was jaundiced and had elevated alkaline phosphatase and transaminases. After exclusion of an intra-abdominal fluid collection, a vascular problem, and infectious or autoimmune liver disease, a liver biopsy was performed. The biopsy revealed centrizonal bilirubinostasis, a portal infiltrate rich in eosinophils and cholangitis. Lymphocyte transformation tests for piperacillin and imipenem/cilastatin were positive, suggesting an immunological mechanism for the observed hepatopathy. Cholestasis gradually decreased but was detectable for several weeks. The patient had a full clinical and biochemical recovery after 3 months. We conclude that short-term therapy with piperacillin, imipenem/cilastatin or the combination of these drugs can lead to the same type of hepatopathy as described for amoxycillin/clavulanic acid or antistaphylococcal penicillins. Liver biopsy and positive lymphocyte transformation are compatible with an immunological mechanism.
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PMID:Cholangiopathy after short-term administration of piperacillin and imipenem/cilastatin. 1142 85

Hyperlipidemia with a marked increase of low-density lipoprotein (LDL) and high- density lipoprotein (HDL) cholesterol levels is a common feature in patients with chronic cholestatic liver disease. Excess morbidity and mortality from cardiovascular disease has not been reported in these patients. This may be due to the particular lipoprotein pattern observed during chronic cholestasis, characterized by elevated serum HDL cholesterol, which may have a cardioprotective effect. However, in a subgroup of patients with chronic cholestasis, hyperlipidemia is characterized by markedly elevated LDL levels with normal or low HDL levels, probably reflecting hypercholesterolemia with coexisting familial and nutritional origins. Ursodeoxycholic acid, the only drug approved for the treatment of chronic cholestatic liver diseases, has been shown to slightly decrease serum cholesterol concentrations. However, the extent of LDL reduction by ursodeoxycholic acid may be insufficient to protect this subgroup of patients from increased cardiovascular risk. Patients in this subgroup probably would benefit from dietary modification, weight loss, and the administration of specific lipid-lowering drugs. Cholestyramine, which is the first-line treatment for pruritus in chronic cholestasis, may be also indicated for its cholesterol-lowering capacity in patients with hypercholesterolemia who complain of pruritus. Administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (simvastatin or pravastatin, 20 mg/d) should be limited to hypercholesterolemic patients with mild chronic cholestatic liver diseases in whom HDL serum levels are below the protective range or if additional risk factors for cardiovascular diseases are present.
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PMID:Hyperlipidemia in Chronic Cholestatic Liver Disease. 1146 68

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


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