Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty of 320 patients with Wilson's disease initially presented with chemical and laboratory features of chronic active hepatitis, confirmed histologically in 17. When first seen, cirrhosis was present in all 20 and was complicated by ascites and/or jaundice in 11. Within 1 week to 8 years of the onset of over liver disease the diagnosis of Wilson's disease was established, and treatment with D-penicillamine was promptly initiated in 19 patients. One man refused treatment and died 4 months later. Treated patients received D-penicillamine or trientine for a total of 264 patient-years (median, 14 patient-years). Abnormal water retention, for which salt restriction and diuretics were added to penicillamine or trientine, disappeared in all but 1 of the patients so affected. Symptomatic improvement and virtually normal levels of serum albumin, bilirubin, aspartate aminotransferase, and alanine aminotransferase followed within 1 year in the majority of subjects. One woman died after 9 months of treatment. Two patients, who became noncompliant with the therapeutic regimen after 9 and 17 years of successful pharmacological treatment, required liver transplants. These results indicate that the prognosis of specifically treated Wilsonian chronic active hepatitis is very good in spite of the presence of cirrhosis.
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PMID:Prognosis of Wilsonian chronic active hepatitis. 199 98

Establishing a diagnosis of fulminant Wilson's disease can be difficult because Kayser-Fleischer rings may not be present and parameters of copper metabolism, including serum and urinary copper, and serum ceruloplasmin levels are neither specific nor diagnostic. In this study, ratios of both the serum alkaline phosphatase to total bilirubin and aspartate transaminase to alanine transaminase were constructed to evaluate their usefulness in differentiating fulminant hepatic failure caused by Wilson's disease (n = 6) from other etiologies (n = 43). An analysis of the data showed that cutoff values of less than 2.0 for the alkaline phosphatase-total bilirubin ratio and greater than 4.0 for the aspartate transaminase ratio were associated with a diagnosis of fulminant hepatic failure caused by Wilson's disease only (P less than 0.001). The alkaline phosphatase-total bilirubin ratio of less than 2.0 provided 100% sensitivity and specificity in identifying fulminant hepatic failure caused by Wilson's disease from other types of fulminant hepatic failure.
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PMID:Clinical differentiation of fulminant Wilsonian hepatitis from other causes of hepatic failure. 200 14

As the results of treatment in Wilson's disease are so dependent on the stage at which penicillamine therapy is started, the antecedent history in 34 patients with Wilson's disease was analysed with particular respect to the earliest manifestations of the disease. Lethargy and anorexia (70%) jaundice (56%) and abdominal pain (48%) were the commonest symptoms and less common were intellectual deterioration (22%) and recurrent epistaxes (22%). The duration of symptoms before diagnosis ranged from five days to three years (mean 10.5 months) and in only five of the patients was the diagnosis established before referral. Analysis of the physical signs at presentation showed hepatomegaly (81%) and splenomegaly (70%) to be common and the only signs which were significantly more common in the 13 fatal cases were jaundice and ascites. In three of these and in one other patient who survived the clinical course was exceptionally severe and was indistinguishable from fulminant hepatic failure. Based on the severity of abnormality of serum aspartate aminotransferase, bilirubin, and prothrombin time on admission a prognostic index was derived which enabled complete separation of fatal and nonfatal cases and when subsequently used in a further nine index cases correctly predicted the outcome. Two further cases found to have indices in the fatal category did well after liver transplantation, which needs to be considered as soon as the diagnosis is established in cases with such severe liver damage.
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PMID:Wilson's disease: clinical presentation and use of prognostic index. 379 21

Triethylene tetramine dihydrochloride (trien) is a copper chelating agent used as the alternative drug of choice in the treatment of Wilson's disease. Because of its apparent safety, we have used the drug in 4 patients with primary biliary cirrhosis in whom penicillamine had to be withdrawn because of serious side effects. Trien is an effective cupruretic drug in primary biliary cirrhosis, but its use is limited by the occurrence of side effects that occurred in all 4 patients. Three patients developed gastrointestinal side effects, and one of these patients developed a skin rash. The 4th patient developed acute rhabdomyolysis within 48 hr of receiving the first dose of the drug. One patient tolerated therapy for 20 wk, and, although her liver copper concentration did not show a marked fall, aspartate transaminase levels fell, and her IgM concentration fell to normal. Trien is an unsuitable copper chelating drug in primary biliary cirrhosis, although it remains the alternative drug of choice in Wilson's disease.
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PMID:Triethylene tetramine dihydrochloride toxicity in primary biliary cirrhosis. 644 5

Although Wilson's Disease is a treatable disorder, 9 of 15 cases referred with undiagnosed liver disease in the present series died in 3 to 53 days of admission. We have reviewed these cases to identify features that would allow earlier diagnosis and improvement in management. The presenting symptoms were lethargy and malaise (11 cases), jaundice (11), abdominal pain (9), and deteriorating school performance (4). At diagnosis, all fatal cases had jaundice and ascites, while only one of the 6 survivors had ascites and two had jaundice. Evidence of hemolysis was found in 3 fatal cases and 5 survivors. Serum bilirubin concentrations, aspartate transaminase, and prolongation of prothrombin time were significantly more abnormal in the fatal cases (p less than 0.01) as compared with the survivors. Cirrhosis was present in all fatal cases and in 2 of the 6 survivors. Wilson's Disease must be excluded in children presenting with frank liver disease as well as those with hemolytic anemia, persisting lethargy, abdominal pain, or deteriorating school performance.
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PMID:Wilson's disease in childhood. Variability of clinical presentation. 661 55

In primary biliary cirrhosis (PBC) liver copper retention occurs as a complication of cholestasis. By analogy with Wilson's disease, it has been suggested that copper retention is hepatotoxic in PBC, and this has been the rationale for the use of D-penicillamine in this disease. The hypothesis that copper is hepatotoxic in PBC has not been tested and in this study we have evaluated the role of liver copper retention in the pathogenesis of PBC. Sixty-four patients with PBC have been studied. Fifty-four had increased liver copper concentrations. Liver cell synthetic function was well preserved. All the patients had normal prothrombin times, and only two had subnormal serum albumin concentrations. There was no correlation between liver copper concentrations and the degree of liver cell damage assessed biochemically (aspartate transaminase), and histologically. Electron microscopy was performed on liver biopsies from five patients with markedly increased liver copper concentrations. The liver cell ultrastructure was compatible with cholestasis. Liver cells contained electron dense lysosomes, which were shown to contain copper and sulphur by x-ray probe microanalysis. The characteristic organelle changes associated with copper toxicity in Wilson's disease were not observed. The biochemical, histological, and histochemical differences between PBC complicated by liver copper retention, and Wilson's disease, indicates that there are differences in the handling of copper in these disease. In this study we could find no evidence to suggest that copper plays an important role in the pathogenesis of liver dysfunction in PBC.
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PMID:Is copper hepatotoxic in primary biliary cirrhosis? 730 88

At routine determination of serum activities of transaminases (aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased levels are frequently found. An algorithm may be used in the analysis of elevated transaminase levels: after elimination of the most frequent causes of hepatitis (alcoholic hepatitis, chronic hepatitis B and C) and some rare conditions (autoimmune hepatitis, alpha 1-antitrypsin deficiency, haemochromatosis and Wilson's disease), the diagnosis will often be nonalcoholic steatohepatitis. Although nonalcoholic steatohepatitis is considered a stable disease, recent literature shows a progression to cirrhosis in 8-17%. So far, no effective therapeutic strategies are available for nonalcoholic steatohepatitis.
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PMID:[Management of asymptomatic elevated serum aminotransferase levels, particularly in nonalcoholic steatohepatitis]. 1032 Dec 58

A candidate gene (ATP7B) for Wilson's disease, an autosomal recessive disorder of copper transport, has recently been identified. We examined the ATP7B gene in two Japanese sisters with Wilson's disease presenting with fulminant hepatic failure but who did not exhibit Kayser-Fleischer rings or abnormal neurological findings. Genomic DNA was isolated from the whole blood of the patients and their family. Entire exons of ATP7B, and their associated splice junctions, were amplified by polymerase chain reaction. The sequencing of all exons was performed by a non-radioactive sequencing method. The sequencing of exon 12 of ATP7B revealed a 9-bp deletion. The mutation deleted 922Gly, 923Tyr, and 924Phe, and three residues conserved in the Menkes gene, ATP7A, located in the fifth transmembrane region. Of the 14 family members tested, 7 were normal and 7 were heterozygous for the deletion. Mean serum copper and cerulopasmin levels were significantly lower in the family members who were heterozygous for the deletion than in the normal family members, and two heterozygous family members showed abnormally low ceruloplasmin levels; however, there were no differences in mean aspartate aminotransferase or alanine aminotransferase levels between the two groups.
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PMID:A new variant deletion of a copper-transporting P-type ATPase gene found in patients with Wilson's disease presenting with fulminant hepatic failure. 1077 57

We describe two females, 15 and 23 years old, respectively, who presented with classical features of Wilson's disease (WD) and several features of autoimmune hepatitis (AIH). The first patient was initially diagnosed as AIH and treated with prednisolone which caused clinical improvement, with an increase of serum albumin from 22 to 30 g/L, and a decrease of aspartate aminotransferase from 103 to 47 U/L. Subsequent diagnosis of WD and introduction of penicillamine gave excellent improvement and complete normalization of liver function tests. The second patient, at first also diagnosed as having AIH, was treated with steroids and azathioprine with initial improvement, but subsequent deterioration. The diagnosis of WD was made 2 years after initial diagnosis of AIH, as the patient reached end-stage liver disease and required a transplant. Therefore, d-penicillamine treatment was not attempted. We conclude that, in patients with AIH, a thorough screening for WD is necessary, particularly when the response to steroid therapy is poor. Conversely, in patients suffering from WD with superimposed features of AIH, a combination of steroids and penicillamine may be of benefit.
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PMID:Wilson's disease with superimposed autoimmune features: report of two cases and review. 1467 55

The Long-Evans Cinnamon (LEC) rats accumulate excess copper (Cu) in the liver in a manner similar to patients with Wilson's disease (WD) and spontaneously develop acute hepatitis with severe jaundice. Although hydroxyl radicals (*OH) have been proposed to be a cause of hepatitis by the accumulation of Cu, it is not clear whether or not *OH can be produced in the liver of hepatitic LEC rats in vivo and also can be involved in the onset of hepatitis. In the present study, *OH production in plasma and liver of hepatitic LEC rats was quantified by trapping *OH with salicylic acid (SA) as 2, 3-dihydroxybenzoic acid (2, 3-DHBA). The ratios of 2, 3-DHBA/SA were significantly higher in plasma and liver of hepatitic LEC rats than those of Wistar rats and LEC rats showing no signs of hepatitis. Furthermore, the ratios of 2, 3-DHBA/SA in plasma and liver of hepatitic LEC rats were almost the same as those of Wistar rats treated orally with CuSO(4) (0.5 mmol/kg) 2 h before acetylsalicylic acid (ASA) injection. We also evaluated the protective effects of D-mannitol (a *OH scavenger) treatment against acute hepatitis in LEC rats. D-mannitol (500 mg/kg) was administered intraperitoneally to 10-week-old LEC rats for 3 weeks. D-mannitol treatment suppressed the increases in serum aspartate aminotransferase activity and total bilirubin concentration. In addition, D-mannitol treatment significantly reduced hepatic mitochondrial lipid peroxidation, which is thought to be important in the pathogenesis of Cu-induced hepatotoxicity. These observations suggest that accelerated generation of *OH catalyzed by free Cu in the liver may, at least in part, play a role in the pathogenesis of acute hepatitis in LEC rats.
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PMID:In vivo evidence for accelerated generation of hydroxyl radicals in liver of Long-Evans Cinnamon (LEC) rats with acute hepatitis. 1118 25


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