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)

Progressive familial intrahepatic cholestasis (PFIC) is a lethal inherited childhood cholestasis of hepatocellular origin. Different subtypes of PFIC have been described according to serum gamma-glutamyl transpeptidase (GGT) activity. There is currently no effective medical therapy available for children with PFIC. We report on 39 patients with PFIC who received ursodeoxycholic acid (UDCA) orally (20-30 mg/kg b.w./day) for a period of 2 to 4 years. Group 1 (n = 26) consisted of children with normal GGT activity, and group 2 (n = 13) of children with high GGT activity. Within group 1, liver tests normalized in 11 children, improved in 5, and stabilized or worsened in 10. Within group 2, liver tests normalized in six children, improved in four, and stabilized or worsened in three. Improvement of parameters was associated with an enrichment of the circulating pool of bile acids with UDCA. Hepatosplenomegaly and pruritus disappeared or diminished in children in whom liver tests normalized. In nine of these children, liver tests worsened and normalized again after stopping and restarting UDCA. Liver histology assessed in four children after normalization of liver tests and 2 years of treatment showed a decrease in fibrosis. We conclude that UDCA should be considered in the initial therapeutic management of children with PFIC, because it appears effective in resolving or improving the liver function and the clinical status of a fair proportion of children. Chronic UDCA therapy might thus avoid the need for liver transplantation in some children with PFIC.
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PMID:Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. 904 90

The beneficial effect of ursodeoxycholic add have been documented in adults but experience with this agent is limited in the pediatric population. The objective of this study was to evaluate ursodeoxycholic acid treatment in children with cholestatic liver disease. Twenty-four patients with intrahepatic cholestasis (neonatal hepatitis 7, Byler disease 7, idiopathic intrahepatic cholestasis 10) whose ages ranged from 1.5 months to 15 years were treated with ursodeoxycholic acid (15-20 mg/kg/day) for 12 months. Liver biopsy was performed initially on all patients and on 17 at the end of the twelve months. The outcome was evaluated by monitoring clinical and biochemical markers of cholestasis, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, cholesterol, total serum tasting bile acids and total and conjugated bilirubin at entry and every three months of treatment. Pruritus was ameliorated in all patients; there was complete disappearance of itching in 16.7 percent. There were significant decreases in mean serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin and gamma-glutamyl transpeptidase. Liver biopsy specimens showed a significant improvement in the cholestasis but not in fibrosis. No adverse effects of therapy were noted. The improvements in the clinical and biochemical parameters and tolerability of the drug suggest that ursodeoxycholic acid is a safe and effective treatment in children with intrahepatic cholestasis.
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PMID:Ursodeoxycholic acid therapy in children with cholestatic liver disease. 1077 Jun 81

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

Abnormal liver function in thyroid disorders may be secondary to thyrotoxicosis or to autoimmune injury to the liver. We report the case of a 36-year-old female who developed jaundice and pruritus with mild cholestasis and moderately elevated transaminase levels. The diagnosis of Graves' disease was made shortly thereafter. Laboratory findings were: alanine and aspartate aminotransferase 219 (IU/I (N: 9-50) and 102 IU/I (N: 10-15) respectively, alkaline phosphatase 336 IU/I (N: 40-135), bilirubin 24 micromol/I (N: 2-23), and gamma-glutamyl transpeptidase 232 IU/I (N: 9-43). Abdominal ultrasonography showed normal bile ducts; echocardiography ruled out heart failure; viral and autoimmune markers for hepatitis and cirrhosis were negative. Percutaneous liver biopsy showed moderate intrahepatic steatosis, anisokaryosis, lymphocyte infiltration in the portal areas, and Kupffer cell hyperplasia. Outcome was favorable after seven months of iodine therapy, confirming the diagnosis of thyrotoxicosis hepatitis.
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PMID:[Thyrotoxicosis hepatitis: a case report]. 1145 76

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritus, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.
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PMID:Autoimmune cholangitis in a patient with thymoma. 1548 46

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.
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PMID:Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum. 1556 72

We report a case of acute hepatotoxicity in a 42-year-old woman after administration of clindamycin for a dental infection. After 6 d of treatment, she had fatigue, nausea, vomiting, anorexia, pruritus and jaundice. Her laboratory analysis showed alanine aminotransferase (ALT), 1795 IU/L (normal range 0-40); aspartate aminotransferase (AST), 1337 IU/L (normal range 5-34); alkaline phosphatase (ALP), 339 IU/L (normal range 40-150); gamma-glutamyl transpeptidase (GGT), 148 IU/L (normal range 9-64 IU/L); total bilirubin, 4.1 mg/dL; direct bilirubin, 2.9 mg/dL and prothrombin time (PT), 13.5 s, with international normalized ratio (INR), 1.04. She was hospitalized, with immediate drug discontinuation. Her liver biopsy specimen showed mixed-type (both hepatocellular and cholestatic) hepatic injury, compatible with a diagnosis of drug-induced hepatitis. An objective causality assessment using the Naranjo probability scale suggested that clindamycin was the probable cause of the acute hepatitis. In susceptible individuals, clindamycin use may lead to acute mixed-type liver toxicity. Complete recovery may be possible if the drug is discontinued before severe liver injury is established.
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PMID:Clindamycin-induced acute cholestatic hepatitis. 1787 18

Inborn errors of bile acid synthesis are rare genetic disorders that can present as neonatal cholestasis, neurologic disease or fat-soluble-vitamin deficiencies. There are nine known defects of bile acid synthesis, including oxysterol 7alpha-hydroxylase deficiency, Delta(4)-3-oxosteroid-5beta-reductase deficiency, 3beta-hydroxy-Delta(5)-C(27)-steroid dehydrogenase deficiency, cerebrotendinous xanthomatosis (also known as sterol 27-hydroxylase deficiency), alpha-methylacyl-CoA racemase deficiency, and Zellweger syndrome (also known as cerebrohepatorenal syndrome). These diseases are characterized by a failure to produce normal bile acids and an accumulation of unusual bile acids and bile acid intermediaries. Individuals with inborn errors of bile acid synthesis generally present with the hallmark features of normal or low serum bile acid concentrations, normal gamma-glutamyl transpeptidase concentrations and the absence of pruritus. Failure to diagnose any of these conditions can result in liver failure or progressive chronic liver disease. If recognized early, many patients can have a remarkable clinical response to oral bile acid therapy.
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PMID:Mechanisms of disease: Inborn errors of bile acid synthesis. 1857 77

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomic-recessive inherited cholestatic disorders that begin in the neonatal period or in the first years of life. There are three types of PFIC defined by different mutations located in the gene responsible for the bile flow through the intrahepatic canalicular transporter system. These disorders usually present in children or young adults and the main clinical manifestations are cholestasis, jaundice and pruritus, and they progress slowly towards liver fibrosis in adult life. PFIC diagnosis is based on clinical suspicion, biochemical findings (that include normal gamma-glutamyl transpeptidase in type 1 and 2, but increased levels in type 3), image techniques that rule-out other disorders, and histological confirmation. Initial treatment consists of symptomatic relief of cholestatic symptoms with choleretic agents (urso-deoxycholic acid). Partial biliary derivation and ileal bypass are intermediate therapeutic options. In case of no response to these treatments, liver transplantation is indicated. We report the case of a neonate with PFIC type 2 presenting as a liver failure.
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PMID:[Progressive familial intrahepatic cholestasis presenting as liver failure]. 1981 57

Primary biliary cirrhosis is often associated with autoimmune diseases. However, its association with pernicious anemia has rarely been reported.We report a case of a 68-year-old woman who presented jaundice and pruritus. Mildly elevated serum levels of alkaline phosphatase and gamma-glutamyl transpeptidase were detected. The titer of anti-mitochondrial M(2 )anti-body was elevated. Histology of liver biopsy showed features of primary biliary cirrhosis. In addition, aregenerative macrocytic anemia was found in the full blood count. The diagnosis of pernicious anemia was established by megaloblastosis in bone marrow, atrophic gastritis without Helicobacter pylori, low level of vitamin B(12 )and good response to treatment regimen of vitamin B(12). The association of primary biliary cirrhosis and pernicious anemia is unlikely to be casual and may be explained by autoimmune mechanism commonly shared by the diseases.
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PMID:A case of primary biliary cirrhosis associated with pernicious anemia: a case report. 2014 39


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