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 biliary cirrhosis is a chronic liver disease of unknown etiology characterized by slowly progressive intrahepatic cholestasis due to an inflammatory destruction of small intrahepatic bile ducts. The clinical course of PBC is variable ranging from a few years in rapidly progressive cases to a normal life-expectancy in a proportion of asymptomatic cases. The typical patient is a middle-aged woman who may present with pruritus, increasing pigmentation of the skin, and eventually jaundice. The level of serum alkaline phosphatase is almost invariably elevated, serum mitochondrial antibodies are present in more than 90 per cent, and an elevated serum IgM is usually present. PBC is associated with many immunologic abnormalities and appears to be a classic autoimmune disease. Some of the immune defects may be epiphenomena; others such as a marked defect in suppressor T cell function seem to be related to the pathogenesis of the disease. All drug therapy that is aimed at slowing the disease process is experimental. A place for immunosuppressive drugs in the management of PBC would be anticipated. However, no drug has to date been definitively shown to have a beneficial effect on the disease. Currently, the main treatments used are aimed at preventing or correcting the complications of intractable cholestasis. Patients with PBC and evidence of hepatic decompensation and/or poor quality of life make good candidates for liver transplantation. The current aim of therapy is to find an effective regime of immunosuppression that will make hepatic transplantation redundant for this disease.
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PMID:Primary biliary cirrhosis. 265 67

Proposed mechanisms, clinical features, prevalence, and treatment of phenothiazine-induced cholestatic jaundice are reviewed, and interactions between phenothiazines and other drugs that could theoretically alter the risk of cholestasis are described. Phenothiazine-induced jaundice is classified as a form of cholestatic hepatocanalicular hepatotoxicity and as an acute liver disease. Occasionally cholestatic jaundice may progress to chronic liver disease. The mechanism of hepatotoxicity is not completely understood but may involve a combination of physiochemical, immune, and direct toxic effects. Based on proposed mechanisms, concomitant use of drugs that alter microsomal hepatic enzyme function or have metabolic pathways that interfere with or overlap with those of the phenothiazines could be expected to potentiate or reduce the risk of cholestasis. The estimated prevalence of jaundice with chlorpromazine is 1-2%. The prevalence of jaundice with other phenothiazines is probably similar. The onset of jaundice usually occurs during the first one to four weeks of therapy. In most cases, discontinuation of the offending drug is the only treatment required. Jaundice usually resolves without sequelae two to eight weeks later. Pruritus can be relieved by topical corticosteroid or analgesic therapies or by oral antihistamines or bile acid sequestrants if topical therapy is ineffective. Whenever possible, reinstitution of neuroleptic therapy should be delayed until the reaction has resolved. Selection of a nonphenothiazine neuroleptic agent may be preferred. Phenothiazine-induced cholestatic jaundice occurs relatively infrequently and is usually self-limited; topical agents and oral antihistamines can alleviate the discomfort associated with the reaction.
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PMID:Phenothiazine-induced cholestatic jaundice. 290 41

A case report is presented of a 43-year-old woman with generalized peliosis hepatitis that developed during longterm use of oral contraceptives (OCs). The patient had been in good health until the last 2 years when she began to experience vague epigastric pains and a feeling of abdominal distension. Several months prior to admission, she had started to complain of itching and fatigue. There was no history of dark urine, white stools, or hepatitis. On physical examination, no jaundice or cutaneous stigmata of chronic liver disease were observed. Laboratory studies showed a normal erythrocyte sedimentation rate and hematological blood count. A radionuclide study of the liver showed hepatomegaly; especially the left lobe was enlarged. A computerized tomographic scan of the liver showed multiple areas of decreased density in both of the enlarged lobes. There was no evidence of a tumor. Selective transfemoral angiography of the celiac artery also showed hepatic enlargement but no signs of a space-occupying lesion. At laparoscopy, the liver was grossly enlarged and had a lumpy appearance, but again there were no signs of a tumor. No evidence of veno-occlusive disease or hepatocellular adenoma was found. The diagnosis was peliosis hepatitis. The OCs were withdrawn, and the patient was discharged. Regular follow-up in the outpatient department showed no decrease in the size of the liver. The alkaline phosphatase level rose. The fatigue became worse, and cholestyramine was prescribed for progressive itching. In September 1980, the patient was admitted for reevaluation. A repeated CT scan and angiography of the liver again yielded no evidence of a tumor. Esophagoscopy showed the presence of varices grade 2. The liver at laparoscopy had the same appearance as it had in 1976. Histological examination of a biopsy specimen showed occasional dilated sinusoids and locally marked periportal and intralobular fibrosis. No regeneration nodules were found. The diagnosis was liver fibrosis. The patient's condition deteriorated gradually in the following years. She experienced increasing fatigue. Steatorrhea developed, and the patient lost weight. She needed increasing doses of cholestyramine and oral supplementation of vitamins A, D, and K. She was admitted for a 3rd time in February 1985. Esophagoscopy revealed varices grade 4. A CT scan of the liver showed no change. The patient successfully underwent an orthotopic liver transplantation in January 1987. The diagnosis of peliosis hepatis was well documented in this patient.
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PMID:Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives. 312 33

A survey of vitamin D status in 152 patients with chronic gastrointestinal conditions and 104 patients with chronic liver diseases is presented. Mild deficiency was common and severe deficiency, as judged by plasma 25-OHD levels less than 8 nmol/l, was encountered in every disease category tested. In the gastrointestinal disease patients, deficiency was significantly more common in patients following gastroenterostomy than other gastric surgery, in patients with active Crohn's disease than in those with inactive disease and in patients with chronic pancreatitis or pancreatic carcinoma with cholestatic features than in those without cholestatic features. Deficiency was as common in patients with Crohn's disease who had not been treated surgically as in those who had. There was no significant correlation between plasma 25-OHD levels and any laboratory index of malabsorption or malnutrition except for serum albumin in the gastric surgery patients, haemoglobin and ESR in the Crohn's disease patients and albumin and vitamin E in the group of patients with gastrointestinal disorders taken as a whole. In the chronic liver disease patients, those with late primary biliary cirrhosis had lower plasma 25-OHD levels than those with histological Stage I and II disease who all had normal levels, and those with pruritus and jaundice were more commonly severely deficient. Whatever the underlying disease process, patients with other coincidental medical conditions were much more likely to be deficient as were patients with cholestasis. Evidence of secondary hyperparathyroidism and osteomalacia on bone histology indicated the clinical relevance of the vitamin D deficiency. This study showed no relationship between abnormal plasma vitamin D binding protein levels and vitamin deficiency.
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PMID:A survey of vitamin D deficiency in gastrointestinal and liver disorders. 654

An effective hepatic assist system could serve as a bridge to transplantation or to treat acute or chronic hepatic failure. Early nonbiological approaches focused on the removal of low molecular weight toxins by dialysis or hemoperfusion, such as over charcoals or resins. This approach led to clinical trials that showed varying degrees of success. Introduction of more porous membranes and blood separation technologies stimulated the development of plasma exchange, on-line plasma fractionation technologies with sorbents and membranes, and other schemes of sorbent-blood interactions based on the principles of dialysis and hemofiltration with sorbent perfusion. Although detoxification of blood has improved the prognosis for acute liver failure, key issues of when to initiate treatment and by which method need to be resolved. In chronic liver disease, blood detoxification can be applied in patients intractable to conventional therapies and for some awaiting transplantation to relieve disease symptoms such as pruritus, jaundice, elevated bile acids, hyperbilirubinemia, endotoxemia, and hypercholesterolemia. Although biological support is considered the ideal, nonbiological techniques can be useful because hepatocytes possess a regenerative capacity and temporary support is helpful. Available nonbiological liver support technologies can substitute for select liver functions in acute and chronic disease.
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PMID:Nonbiological liver support: historic overview. 803 7

Primary biliary cirrhosis (PBC) is uncommonly described from Asia and it is an extremely rare cause of chronic liver disease in India. Six first generation migrant Asian patients with PBC were seen at the Liver Unit, Queen Elizabeth Hospital, Birmingham during the period 1982-94. All were women and their ages at presentation ranged from 31 to 63 (median 40) years. All were symptomatic for a median of 6 months prior to referral to the unit for transplantation. Itching with or without jaundice was a common presenting feature. Diagnosis was based on raised serum IgM levels, presence of antimitochondrial antibody (titres 100-400) and diagnostic histology. Only one patients had an associated autoimmune disease (coeliac disease). Serum bilirubin level was above 100 mumol/l at the time of presentation in four patients. Four of these patients with end-stage PBC are first generation migrants from south Asia, who have been resident in the West Midlands for the past 10 to 34 years. The total south Asian population of the West Midlands is 276,754; thus, from these four patients alone the estimated prevalence of PBC in the migrant south Asian population is at least 14 per million. However, such data cannot be used to give any accurate assessment of prevalence, for which a population screening programme is required. A higher incidence in the migrant population than in their countries of origin is compatible with an environmental aetiology.
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PMID:End-stage primary biliary cirrhosis in a first generation migrant south Asian population. 885 55

Doing a liver test before the use of OCs is advisable for women who face risks, those with previous history of liver disease and familial benign hyperbilirubinemia. For those women who have a negative anamnesis with regard to each of these risk factors, it is not necessary to carry out a liver test before prescribing OCs. The risk of worsening latent chronic hepatitis is very small, and the occurrence of subsequent liver lesions is extremely rare. It is sufficient to carry out the test in women at risk after 3 months and after 1 year of OC use. This applies to patients with intensified cholestatic reactions, which have been asymptomatic, as well as to patients with latent chronic liver disease. The liver test needs to be repeated at regular intervals only when the following clinical symptoms are present: dyspepsia, pruritus, and icterus. Benign and malignant liver tumors cannot be confirmed by liver tests; therefore, there is no justification for this. On the other hand, it is believed that the very low incidence of liver tumors in a small group of women who continue to use OCs for more than 8 years would meet the indication for liver examination. Absolute contraindications for the use of OCs with regard to liver function are considered only for liver disease with prolonged higher liver test values, cholestatic jaundice in pregnancy, and liver tumor.
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PMID:[The effect of hormonal contraception on liver function]. 941 Apr 23

Recurrent familial intrahepatic cholestasis is an autosomal recessive disorder characterized by episodes of severe pruritus and jaundice lasting for weeks to months without extrahepatic bile duct obstruction. Symptom-free intervals may last for months to years, and chronic liver damage does not develop. We recently studied four of the five patients from the Faeroe Islands described by us 30 years ago (one had recently died) and an additional five patients that were identified after the initial report. The episodes of cholestasis were more frequent and severe in patients with early onset, but tended to reduce in frequency with age. The youngest patient, aged 25 years, who had had 16 episodes each lasting about 6 months, had a liver transplant after which no further episodes were recorded (1 year after surgery). Signs of chronic liver disease were absent in all patients. The FIC1 gene was investigated for mutations in the surviving patients. A single mutation (I661T) was found on both chromosomes in all nine patients, indicating that they are genetically identical for the disease-causing defect. Nevertheless, considerable differences among patients were observed clinically.
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PMID:Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic heterogeneity but genetic homogeneity. 991 28

This study sought to identify any benefit of routine liver function tests (LFTs) in chronically ill, geriatric patients and to assess which patients require evaluation for abnormal LFT levels. A retrospective chart review was carried out on 268 consecutive patients (M:F = 1.2, mean age 77 years, range 61-98 years) presenting for acute care from a long-term care facility. All were without jaundice, right upper quadrant pain, pruritus, bruising, or signs of chronic liver disease. The degree of LFT abnormality (aspartate aminotransferase, alanine aminotransferase, total bilirubin, or alkaline phosphatase) during admission was compared to the clinical diagnosis at the time of discharge. The most common diagnoses were pneumonia, urinary tract infection, and peripheral or coronary disease in 186 (60%). Thirty-seven patients (14%) had elevated LFT levels on admission. The levels normalized within 2 days in 26 of these patients, 25 of whom had a history of vascular disease (96%). Of the 11 remaining patients, 4 had coexistent vascular disease (36%), and 5 had LFT levels twice normal (none with vascular disease) and underwent abdominal ultrasound. One patient had a common bile duct stone successfully extracted. Enzyme abnormalities were due to hepatitis B or medication use in 10 of 11 patients. No patient had liver biopsy. All but one of the 268 patients were discharged without further evaluation. Over one year of follow up, no patient returned for a liver-related problem. Based on these findings, only those patients with LFT levels that are twice normal and which do not normalize within 2 days warrant further evaluation. Transient LFT abnormalities may be due to decreased liver perfusion.
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PMID:Outcomes of routine testing of liver enzymes in institutionalized geriatric patients. 1016 61

Recurrent familial intrahepatic cholestasis is an autosomal recessive disorder characterized by episodes of severe pruritus and jaundice lasting for weeks to months without extrahepatic bile duct obstruction. Symptom-free intervals may last for months to years, and chronic liver damage does not develop. We recently studied four of the five patients from the Faeroe Islands described by us 30 years ago (one had recently died), and a further five patients who were identified after the initial report. The episodes of cholestasis were more frequent and severe in patients with early onset, but tended to reduce in frequency with age. The youngest patient, aged 25 years, who had had 16 episodes, each lasting about six months, had a liver transplant after which no further episodes were recorded (one year after surgery). Signs of chronic liver disease were absent in all patients. The FIC1 gene was investigated for mutations in the surviving patients. A single mutation (I661T) was found on both chromosomes in all 9 patients, indicating that they are genetically identical for the disease causing defect. Nevertheless, considerable differences between patients were observed clinically.
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PMID:[Recurrent familial intrahepatic cholestasis in the Faroe Islands]. 1077 15


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