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)

The effects of rifampicin treatment (10 mg.kg-1.day-1) on pruritus and cholestasis were evaluated in 16 patients with primary biliary cirrhosis and pruritus followed up for 2-24 months. Assessment of pruritus severity, liver tests, aminopyrine breath test, and bile acids was done at 2 weeks and every 3 months after the beginning of the study. Two patients (12.5%) were withdrawn after 2 months of treatment because they had hepatitis caused by rifampicin. Four patients were withdrawn after 4 months because of liver transplantation (3 cases) and the development of leg edema associated with administration of rifampicin. The remaining 10 patients received therapy for 14.4 +/- 0.7 months and did not experience side effects. Pruritus improved in all patients and disappeared in 11 patients (79%) after 3 months of treatment. Moreover, all patients followed up for more than 1 year were free of pruritus. The alkaline phosphatase level decreased significantly, and the aminopyrine breath test results increased significantly after 2 weeks of treatment (P less than 0.001) and did not change thereafter. In the 9 patients treated for 15 months, alkaline phosphatase levels decreased to 63% of the basal levels and aminopyrine breath test results increased to 153% of baseline values. Transaminases, gamma-glutamyltransferase, and total bile salt levels decreased significantly after 2 weeks of treatment but returned to baseline after 3 months. No changes in bilirubin and cholesterol levels were observed. It is concluded that long-term rifampicin treatment is effective for relieving pruritus in primary biliary cirrhosis, but liver enzymes should be monitored to detect drug-induced hepatitis.
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PMID:Effects of long-term rifampicin administration in primary biliary cirrhosis. 158 27

We investigated the effects of once-daily oral administration of 10 mg/kg ursodeoxycholic acid (generic name, ursodiol) on elevated serum enzyme activities, bilirubin, cholesterol, bile acids and symptoms in patients with primary sclerosing cholangitis. A 30-mo, open-label, pilot trial was designed to cover four periods: (a) 3 mo of pretreatment observation (period 1), (b) 6 mo on ursodiol (period 2), (c) 3 mo withdrawal of treatment (period 3) and (d) 18 mo of extended retreatment (period 4). Diagnosis was confirmed by cholangiography and liver biopsy specimens. We enrolled 12 patients with persistently elevated pretreatment alkaline phosphatase and gamma-glutamyltransferase levels (at least twice the upper limit of normal), and observed them for a median of 37 mo. Significant reductions in serum total cholesterol levels and in serum enzyme activities indicating cholestasis and hepatocellular injury occurred during ursodiol treatment in both treatment periods 2 and 4 and relapsed with treatment interruption in period 3. Elevated serum bilirubin and symptoms of disabling fatigue, pruritus and diarrhea were improved by ursodiol. Improvements have continued after 2 yr of treatment in 10 patients (1 patient had a transplantation after he relapsed on withdrawal of ursodiol therapy; another died of postoperative complications of colon resection for carcinoma). No other cases of clinical deterioration were observed in the retreatment period. The longer term reductions of alkaline phosphatase, transaminases, bilirubin and cholesterol after 2 yr of treatment were even greater than the initial reductions after 6 mo of treatment. These results justify initiation of larger, controlled clinical trials, with serial morphological evaluations of the liver and biliary tree.
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PMID:Ursodeoxycholic acid for the treatment of primary sclerosing cholangitis: a 30-month pilot study. 193 90

Seven patients developed acute hepatitis after receiving Plethoryl for obesity for 4 to 16 weeks. Jaundice was generally associated with or preceded by asthenia, nausea and pruritus. Serum aminotransferase activities were markedly increased whereas alkaline phosphatase and gamma-glutamyltransferase activities were moderately elevated. There was no hepatic failure. In all cases, Plethoryl administration was promptly discontinued. In 6 cases, jaundice disappeared within 2 to 4 weeks, and recovery occurred within 2 to 5 months. In one case, however, jaundice disappeared within 12 weeks and recovery took 10 months.
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PMID:[Hepatitis probably caused by Plethoryl. Apropos of 7 cases]. 337 97

There have been a few reports of infants with severe neonatal cholestasis related to a defect in primary bile acid synthesis. To assess the importance of such deficiency among children with progressive intrahepatic cholestasis (Byler disease), screening for inborn errors in bile acid synthesis was performed by fast atom bombardment ionization-mass spectrometry of urine samples from 30 affected children. Bile acid analysis revealed a specific fast atom bombardment ionization-mass spectrometry profile for 3 beta-hydroxy-C27 steroid dehydrogenase/isomerase deficiency in five children who had jaundice, hepatosplenomegaly, and fatty stools beginning at ages ranging from 4 to 46 months. None of them had pruritus. Liver function tests showed persistently normal serum gamma-glutamyltransferase activity, low serum cholesterol and vitamin E levels, normal serum bile acid concentrations despite raised serum bilirubin levels, and decreased prothrombin time and clotting factor V. In four of the cases a similar disease was observed in siblings. Liver function returned to normal after oral ursodeoxycholic acid therapy. We conclude that 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency should be considered when idiopathic cholestatic liver disease with clinical features akin to Byler disease is characterized by the association of normal serum gamma-glutamyltransferase activity, normal serum bile acid concentration, absence of pruritus, and a return to normal liver function during ursodeoxycholic acid therapy. Early identification of these children is essential because they benefit from bile acid therapy and might thus avoid the need for liver transplantation.
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PMID:A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency. 791 5

Methotrexate (2.5 mg/day) was used in addition to ursodeoxycholic acid (10-15 mg/kg per day) in 8 female patients with primary biliary cirrhosis. All patients had undergone ursodeoxycholic acid treatment for more than 6 months preceding this study and their serum alkaline phosphatase remained constant at more than 300 U/l for more than 2 months. One patient showed histologic stage I, three stage II, two stage III and two stage IV disease. Within 6 months, fatigue and itching disappeared in all symptomatic patients. Serum alkaline phosphatase activities improved dramatically (621 +/- 299 to 378 +/- 258, mean +/- S.D.) in all but one patient and normalized in four. Serum gamma-glutamyltransferase activities (180 +/- 99 U/l vs. 150 +/- 125 U/l) and immunoglobulin M concentrations (616 +/- 424 vs. 362 +/- 195 mg/dl) also improved. Adverse effects of methotrexate therapy were only regularly observed within the first 2-6 weeks, such as fatigue and transient enhancement of transaminases and serum bile acid concentrations. We conclude that methotrexate may be a highly effective drug for the treatment of primary biliary cirrhosis in patients whose symptoms and/or laboratory liver function tests are not improved enough by ursodeoxycholic acid alone. However, its influence on histology and the natural history of the disease needs to be established.
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PMID:Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. 810 53

Primary sclerosing cholangitis is a cholestatic disease of the liver characterized by progressive fibrotic inflammation and obliteration of the extra- and/or intrahepatic bile ducts. There is no effective therapy. We, therefore, studied the safety and efficacy of ursodeoxycholic acid in patients with primary sclerosing cholangitis with or without additional ulcerative colitis. In a 1-year ursodeoxycholic acid treatment period, which preceded the controlled study period, ursodeoxycholic acid was well tolerated in 22 of 24 patients with ulcerative colitis and in all three patients without ulcerative colitis. In two patients with ulcerative colitis the dose of 750 mg ursodeoxycholic acid/day led to diarrhea, but following reduction of the dose to 500 and 250 mg/day ursodeoxycholic acid was well tolerated. After 1 year of ursodeoxycholic acid treatment, 20 patients were randomly assigned to receive either ursodeoxycholic acid 750 mg/day or placebo. All of them finished a double-blind, placebo-controlled study period. During ursodeoxycholic acid treatment, the liver enzymes improved markedly. The difference in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyltransferase between the placebo and ursodeoxycholic acid group was significant (p < 0.05). Following ursodeoxycholic acid treatment, pruritus and fatigue improved in half of the patients but the difference between the placebo and ursodeoxycholic acid group was not significant. According to the ethical guidelines, after 3 months of placebo treatment, the controlled study had to be discontinued because of a more than twofold increase of serum transaminases in 8/10 patients on placebo. After the end of the controlled study, all patients were continuously treated with ursodeoxycholic acid for up to 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of ursodeoxycholic acid on liver and bile duct disease in primary sclerosing cholangitis. A 3-year pilot study with a placebo-controlled study period. 820 Dec 24

Pregnancy is very uncommon in patients with primary biliary cirrhosis (PBC) and only few reports exist about pregnancy and PBC. However, no data are available on therapy and potential risks of treatment with ursodeoxycholic acid (UDCA) in PBC, especially in the first trimester of pregnancy. Furthermore, it is not known, whether UDCA is secreted into the breast milk during lactation. We report a 41 year old patient with the diagnosis of PBC stage III, who had been treated with UDCA (750 mg/day) for three years. At the time of diagnosis of pregnancy (5th gestational week), UDCA was withdrawn. Within nine days, severe pruritus developed, alkaline phosphatase and gamma-glutamyltransferase increased. UDCA was administered again (750 mg/day). The pruritus disappeared completely within one week. Liver enzymes decreased to baseline values and remained stable throughout the remainder of the pregnancy. No drug-related side effects were observed. Caesarean section for placental insufficiency unrelated to PBC was performed at the 34th week of pregnancy. The newborn thrived normally during a follow-up period of six months. When the patient's breast milk was analyzed by high pressure liquid chromatography, cholic acid, deoxycholic acid and lithocholic acid, but not UDCA were detected in trace amounts. It is concluded that UDCA therapy in PBC may be continued in the early pregnancy and during the breast feeding period. UDCA may be effective for the prevention of cholestasis in PBC during pregnancy.
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PMID:-Therapy with ursodeoxycholic acid in primary biliary cirrhosis in pregnancy-. 865 Sep 73

Benign recurrent intrahepatic cholestasis (BRIC or Summerskill-Walshe-Tygstrup-syndrome) is a rare autosomal recessive form of liver disease, which usually becomes manifest in childhood. Characteristic are recurrent episodes of jaundice and itching of different duration. Number and duration of episodic attack and asymptomatic period develop individually. For diagnosis of BRIC following criteria are proposed: At least three episodes of severe jaundice and pruritus with biochemical evidence of cholestasis, normal intra-and extrahepatic bile ducts on cholangiography, absence of a factor known to produce intrahepatic cholestasis and symptom-free intervals of several months or years. Often the diagnosis of BRIC is made very late and patients have to suffer invasive investigations (explorative laparotomy). Because of the unknown pathophysiological mechanism there is no specific treatment. We report on a 53-year-old patient with jaundice, severe pruritus, vomiting, loss of hair and weight, extreme sleeplessness and intractable cough. At the onset of the attack an increase of serum bilirubin concentration and serum alkaline phosphatase was observed, whereas aspartate and alanine aminotransferase and gamma-glutamyltransferase were normal. Histological findings of liver biopsy revealed accumulation of bile plugs in bile canaliculi. The long-term follow-up of our patient confirms that the prognosis is good.
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PMID:[Follow-up of benign recurrent intrahepatic cholestasis (Summerskill-Walshe-Tygstrup syndrome) over 46 years]. 965 5

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

Recent advances in genetics and in physiopathology of bile composition and excretion have clarified the understanding of progressive familial intrahepatic cholestasis (PFIC). The aim of the present study is to review the experience of our center in terms of diagnosis, management and outcome of 49 pediatric PFIC patients, belonging to the three classical subtypes described. We analyse the clinical, biological, and histological patterns and review the response to the medical and surgical treatment and the global outcome. The only clinical difference between the different subtypes of PFIC patients was the intensity of pruritus. Serum gamma-glutamyltransferase (GGT) and liver histology allowed to differentiate PFIC III from PFIC I and II patients. High levels of biliary bile acids in 2 low-GGT patients was associated with favourable outcome. Response to ursodeoxycholic acid (UDCA) varies from patient to patient and was not associated to a particular subtype of PFIC. In five patients of this cohort, external biliary diversion was performed without improvement. Transplantation is indicated whenever medical treatment fails to restore normal social life, growth and well being of the child and it is associated with excellent survival (> 90%).
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PMID:Fifteen years single center experience in the management of progressive familial intrahepatic cholestasis of infancy. 1572 74


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