Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0008370 (cholestasis)
 9,378 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using routine liver function tests, cholestasis of pregnancy was diagnosed in 86 pregnant women with pruritus. Serum aminotransferase levels were elevated in all cases, ASAT in 99%, and ALAT in 100%. In these patients serum concentrations of cholic, chenodeoxycholic, and deoxycholic acid were determined using a gas chromatographic method and were compared with those in a group of 40 uncomplicated pregnancies. Of these bile acids, cholic acid levels were most frequently elevated, ie, in 92% of the patients. The frequency of elevation of serum levels of alkaline phosphatase, and total and conjugated bilirubin was lower. Thus, it appears that in addition to serum aminotransferase levels the serum cholic acid concentration is a sensitive indicator of cholestasis of pregnancy. The cholestasis series was divided into 3 subgroups of increasing severity of cholestasis as assessed by maternal serum cholic acid levels, and the occurrence of signs of fetal distress was compared between these subgroups. The only intrauterine fetal loss in the series belonged to the severe cholestasis group. The incidence of meconium-stained amniotic fluid also increased significantly in this group, and 21 of the 24 cases with other signs of fetal distress were in the groups of moderate and severe cholestasis.
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PMID:Serum bile acids in cholestasis of pregnancy. 89 1

Seven women, mean age 47.7 years, with primary biliary cirrhosis (6 patients in the II-III stage and I patient in IV stage of the disease) were treated in the course of 16 months with ursodeoxycholic acid (Ursofalk) 500 mg daily. At the end of the 3-d month of treatment the itching had passed in 3 of the patients and in the remaining 4 patients it had substantially decreased. In all patients the subjective complaints, dyspeptic syndrome, appetite and sleep improved. The serum concentrations of bilirubin, copper and cholesterol started to decrease and the serum activity of the enzymes alkaline phosphatase, ALAT and ASAT also decreased. In one patient the treatment was discontinued in the 6-th month because of allergic reaction. After 16 month treatment in the 6 patients who completed the treatment the itching passed and the working capacity improved. The serum concentrations of bilirubin, cholesterol, copper and IgG significantly fell (p less than 0.01), the serum activity of alkaline phosphatase, gamma glutamyl transpeptidase, ALAT and ASAT fell near the upper normal range. The hepatomegaly, splenomegaly, McLagan's flocculation test, serum concentration of IgM and the titer of the specific antimitochondrial antibodies (M2) did not change in spite of the treatment. The results show the ursodeoxycholic acid as a perspective therapeutic means for primary biliary cirrhosis which lowers or overcomes the syndrome of intrahepatic cholestasis and limits the activity of the cirrhotic process in the liver. Ursodeoxycholic acid is well tolerated.
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PMID:[The treatment of primary biliary liver cirrhosis with ursodeoxycholic acid (preliminary report)]. 177 66

Acute hepatotoxicity after administration of 10-1000 mg/kg methotrexate (MTX) to rats was studied by monitoring serum transaminases, liver morphology, and disposition kinetics of MTX and 7-hydroxy-methotrexate (7-OH-MTX). Half the control rats and rats administered 1000 mg/kg MTX, had their bile duct cannulated. One to 2 hr after administration of 1000 mg/kg MTX, 50% of MTX treated bile-drained rats (Ebc) developed cholestasis despite similar or larger initial bile flow rates than those which did not develop cholestasis (Ebn, controls). In Ebc animals, peak serum ASAT and ALAT levels were 6- and 4-fold higher than that of the control rats, and morphologically, prominent hepatocytic changes and grossly dilated bile canaliculi were found. Immediately prior to cholestasis, the Ebc animals reached biliary 7-OH-MTX levels (8.3 +/- 1.3 mM, mean +/- S.E.M.) which were equivalent to the threshold level for precipitation of 7-OH-MTX in rat bile in vitro, and 3-fold higher than the corresponding levels of 7-OH-MTX in the bile of Ebn rats. Ninety-five % of the drug in the precipitated material was 7-OH-MTX. Hence, 7-OH-MTX may play a role in acute MTX hepatotoxicity, a dose-limiting toxicity that may not be counteracted by leukovorin rescue.
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PMID:Acute hepatotoxicity after high-dose methotrexate administration to rats. 177 33

The authors report a case of toxic hepatitis in a woman of 22 years of age in the third trimester of her first pregnancy treated by methyldopa for hypertension of pregnancy which was diagnosed at 33 weeks of amenorrhoea. The prodromal symptoms were mild and consisted of nausea, vomiting and rise in temperature and this phase was associated with febrile jaundice without pruritus and it was only associated with coagulation disorders in the third stage of labour. This was a case of mixed cytolytic hepatitis (ASAT x 3N) and cholestasis (x 1.5N). The outcome was fatal. The patient died three days after delivery following haematemesis and renal failure as well as hepatic encephalopathy. The main diagnostic feature was acute hepatic stasis in spite of the absence of pruritus and the presence of a raised temperature after hematolytic, viral and obstructive causes had been eliminated. Histology confirmed that there was toxic hepatitis. This aetiology was suggested by the timing of the symptoms after MD (methyldopa) had been taken. Elkington described methyldopa hepato-toxicity in 1969. Fatal cases in the literature were in patients who were over 40 years of age. Methyldopa is used in pregnant women because of its safety as far as the fetus is concerned. Mechanism by which it causes toxic hepatitis is a combination of abnormal metabolism (the cytochrome P450 chain produces an antigen) and an immune reaction in response to this antigen and these explain why such severe and potentially fatal forms of the condition exist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fatal toxic hepatitis in pregnancy. A discussion of the role of methyldopa]. 232 42

The study includes 108 patients with acute alcohol hepatitis, 45 patients with cholestasis and 124 healthy controls. In 14 patients (13%) cholestatic acute alcohol hepatitis was found. The patients with cholestatic acute alcohol hepatitis consumed considerably more alcohol than the other patients with acute alcohol hepatitis. The intensive jaundice led half of the patients with cholestatic acute alcohol hepatitis to the infectious diseases clinic and 32% of them to the surgical clinic. The course of the disease was heavy, with disturbed general condition, high temperature, pain in the right subcostal region but without itching. The patients showed higher levels of timol test, cholesterol, LDL-cholesterol, coefficient LDL/HDL-cholesterol, beta-lipoproteins, total lipids, gamma-GTP, ASAT and lower levels of leucocytes, bilirubin, SMC, alkaline phosphatase and LAP than the other patients with cholestasis. The patients with cholestatic acute alcohol hepatitis showed a higher level of total lipids and gamma-GTP than the other patients examined. The confirmation of the diagnosis implies the application of contemporary instrumental and invasive methods. The ultrasound examination is of special importance.
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PMID:[The clinico-laboratory characteristics of the cholestatic form of acute alcoholic hepatitis]. 263 77

In a prospective study carried out on a group of 1210 patients with liver cirrhosis (LC), the diagnosis was based on clinical, biological and histological criteria, as well as on the prognostic significance of 20 clinical, biochemical and histological parameters. The group, including 830 males (68.59%) and 380 females (31.41%), with an average age of 49.27 +/- 13.18 years, was studied during periods of 6 to 16 months, the initial investigations being periodically repeated. The statistical significance of the prognosis factors was studied by uni- and multivariative methods, according to the model of Cox, with the help of an IMB computer. The survival rate for the group studied ranged from 6 to 204 months, with an average period of survival of 38.29 months. The multivariative analysis demonstrated that the prognosis factor with a best correlation with the death power is ascites, which has additional predictive significance in association with encephalopathy and/or jaundice. The multivariative analysis selects as clinical factors of unfavourable prognosis the cholestasis, the hepatocytolytic syndrome, the syndrome of liver deficiency and the age over 50. The limits of the biochemical parameters with unfavourable significance were: bilirubinemia level greater than 3 mg%, ASAT/ALAT = 50.24/70.33 u.i., prothrombinemic index less than 50% and albuminemia greater than 3 g%. The multivariative method proved also superior in appreciating the interrelations of the prognostic factors, emphasizing the significance of the clinical parameters (ascites, encephalopathy, jaundice), while the multivariative analysis differentiated the biochemical prognosis factors (bilirubinemia, ASAT/ALAT, prothrombinemic index, albuminemia) and their level of significance.
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PMID:Study of the prognosis factors in liver cirrhosis. 365 5

In our long-term study of alcoholic chronic pancreatitis (median follow-up time, 10.4 years) 84 of 173 patients (48.6%) developed transient or persistent cholestasis with or without hyperbilirubinemia. We studied the discriminative value of the ASAT/ALAT ratio to differentiate intrahepatic (IHC) and extrahepatic cholestasis (EHC; due to stenosis of the distal common bile duct) in 75 of these patients. In 45 patients with persistent or recurrent cholestasis (group A) the cause of cholestasis was documented by accurate morphological methods. Thirty of the other 39 patients with transient cholestasis (group B) were classified on the basis of the overall clinical evaluation. Of 37 patients with IHC 36 had an ASAT/ALAT ratio of 1.5 or higher (one patient had normal values for both transaminases). Out of 38 patients classified as EHC 29 had an ASAT/ALAT ratio of 1.4 or lower (9 with normal transaminases being excluded). One patient with cholangitis secondary to EHC had a transient elevation of the ASAT/ALAT ratio to above 2.5. Thus our data suggest that in alcoholic chronic pancreatitis associated with cholestasis an ASAT/ALAT ratio of 1.4 or lower (or normal transaminases) usually indicates EHC. Diagnostic study and surgical decompression is mandatory in these cases if EHC persists.
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PMID:Cholestasis in alcoholic chronic pancreatitis. Diagnostic value of the transaminase ratio for differentiation between extra- and intra-hepatic cholestasis. 404 36

The gamma-GT/ASAT (aspartate aminotransferase) and gamma-GT/ALAT (alanine aminotransferase) ratios were examined in 6 children with neonatal hepatitis (NH), 14 children with extrahepatic biliary atresia (EHBA), and 8 children with intrahepatic cholestasis (IHC) (of which 3 with the Aagenaes syndrome). A ratio above 1 is suggestive of EHBA. Both ratios differentiate very well between NH and EHBA, but there is considerable overlap in the enzyme ratios between the EHBA and the IHC groups. Gamma-GT/transaminase ratios may prove to be a useful indicator in the diagnostic work-up of children with liver and biliary tract disease, allowing for early surgery in patients with EHBA, and with a low risk of subjecting NH patients to unnecessary surgery. In our cases the gamma-GT/ALAT ratio separated better between EHBA and IHC than the gamma-GT/ASAT ratio. Furthermore, the case histories made EHBA seem unlikely in two out of three IHC patients with a gamma-GT/ALAT ratio above 1.
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PMID:Liver enzyme ratios in neonatal liver disease. 652 89

In France, prescription of micronized progesterone at high doses of 900 to 1200 mg/day is common practice in the case of preterm delivery, even though this is neither an indication nor a posology given for marketing authorisation. A few cases of gestational pruritus have been reported during such use, associated with cholestasic and/or cytolytic hepatic disorders. We report here the results of a controlled, double-blind study versus a placebo, aimed at assessing the effects on the liver of micronized progesterone administered orally at high doses (900-1200 mg/day), conducted in a population of 201 women presenting moderate menace of preterm delivery during the third trimester of pregnancy. 85 patients received micronized progesterone and 116 the placebo. The increase above normal levels of total biliary acids (TBA) and aminotransferases (ASAT, ALAT), was significantly more frequent in the micronized progesterone than in the placebo group. Among the 26 patients (14%) with a level of TBA superior to 10 mumoles/l during treatment, 18 belonged to the progesterone and 8 to the placebo group (p = 0.004); the 6 patients (3.4%) with increased ASAT were all under micronized progesterone (p < 0.001), as were the 10 patients (5.6%) with increased ALAT (p < 0.001). However, there is no statistically significant difference between the two groups regarding the occurrence of clinical manifestations (icterus, pruritus) which could be attributed to gravid cholestasis. We may conclude from this prospective study that, during the third trimester of pregnancy, micronized progesterone is associated with a significant risk of biological cholestasis. This would suggest that in patients genetically predisposed towards gravid cholestasis, micronized progesterone could be a factor favoursing this disease.
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PMID:[Effects of micronized natural progesterone on the liver during the third trimester of pregnancy]. 911 78

The aim of the present study is to investigate the impact of bile duct reconstruction by a splint technique, a method which has not been sufficiently researched in animals after liver transplantation. Three experimental groups were set up: I = control, sham operation; II = bile duct reconstruction; III = orthotopic rat liver transplantation (ORLT). After bile duct reconstruction, serum levels of ASAT and ALAT in group II revealed a peak on the first postoperative day. The transplanted animals (group III) showed a second peak in liver enzyme levels on the fifth postoperative day; it was significantly higher than in group II. Serum bilirubin was more elevated in the transplant group, with a peak on day 7. Morphological investigations at the end of surgery revealed only intralobular necrosis and reactive changes in the liver capsule (group II); after transplantation (group III), there was also interstitial and intracellular edema, fatty degeneration and disintegration of the sinusoidal lining. One month later, necrosis, bile duct proliferation, cholestasis, cholangitis and vascular alterations were found in groups II and III. Furthermore, an increased rate of hepatocellular and bile duct proliferation was observed. These findings are partly due to the bile duct reconstruction. We recommend that a bile duct reconstruction control group should be included in ORLT experiments.
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PMID:Orthotopic rat liver transplantation and bile duct reconstruction by a splint technique. 940 64


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