Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although rather uncommon and multifactorial in etiology, liver cirrhosis is a severe and often rapidly fatal disease in pediatrics. In our institution, during the last 15 years, 22 children with liver cirrhosis have been followed. The underlying predisposing condition was HBV infection (8 cases), CMV perinatal infection (2 cases), Wilson's disease (4 cases), chronic cholestasis (2 cases) and alcohol abuse (2 cases); in 4 cases no predisposing condition was evident. In all cases the histological examination of the liver was the diagnostic cornerstone. The mean age at diagnosis was 6 years and 8 months, with an early onset especially in the posthepatitis cirrhosis. In 10 out of 22 patients, cirrhosis was not preceded by an history of chronic liver disease. Poor subjective symptomatology was present in 13 of the cases, hepatomegaly in all, splenomegaly in 18 cases, signs of hepatic failure in 13 cases. In all patients various impairments of hepatocellular synthesis were detectable, especially during the period preceding the development of hepatic insufficiency. The mean time to cirrhosis was 5 years. The average duration of the follow up was 3 years and 4 months: during the follow up 6 patients improved, 5 patients showed no clinical or functional modifications of their hepatic disease, 3 patients worsened and 8 died. In order to perform suitable treatment of liver cirrhosis the need of early diagnosis and etiological definition should be emphasized.
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PMID:[Liver cirrhosis in childhood. Considerations on 22 cases with different etiology]. 217 33

The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well-designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven.
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PMID:Current therapy of chronic liver disease. 219 64

A 21 y/o female presented with fulminant hepatic failure and hemolysis. On the basis of the clinical presentation, levels of ceruloplasmin and serum copper a presumptive diagnosis of Wilson's disease was made. In spite of supportive measures and hemodialysis, the patient died one week after admission. Postmortem examination showed cirrhosis and increased copper stores in the liver, corroborating the clinical diagnosis of Wilson's disease. Study of the four siblings revealed that two are carriers, one is healthy and one may have the disease. Wilson's disease is a rare cause of fulminant hepatic failure that must be suspected specially when hemolysis is associated to the clinical picture. This mode of presentation is virtually fatal and early liver transplantation is the best form of therapy.
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PMID:Fulminant Wilson's disease: a report. 222 83

Wilson's disease may present with severe acute hepatocellular failure. The only effective treatment for fulminant Wilson's disease is liver transplantation, which may lead to reversal of the underlying disease. Some patients with cirrhosis who are too ill to undergo orthotopic liver transplantation have been treated with heterotopic liver transplantation. However, use of heterotopic liver transplantation for fulminant hepatocellular failure has not been successful. This case study involves a patient in whom a heterotopic liver transplant was successfully used for treatment of Wilson's disease presenting with fulminant hepatocellular failure.
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PMID:Heterotopic liver transplantation for fulminant Wilson's disease. 222

Hepatolenticular degeneration (Wilson's disease) is a hereditary disease in which metabolic disorder of copper leads to its accumulation in the liver, brain, cornea and kidneys with consequent pathologic changes in those organs. Hereditary mechanism of the disease is autosomal recessive with prevalence of 30-100 per 1,000,000 inhabitants. Etiology of this disease is not yet explained. There are two hypotheses. The first one is that it is the disorder of ceruloplasmine metabolism caused by insufficient synthesis of normal ceruloplasmine, or synthesis of functionally abnormal ceruloplasmine. The second one is: the block of copper biliar excretion which is the consequence of the liver lysosomes functional defect. Pathogenetic mechanism of disease is firstly long-term accumulation of copper in the liver, and later, when the liver depo is full, its releasing in circulation and accumulation in the brain, cornea, kidneys and bones, which causes adequate pathologic changes. Toxic activity of copper is the consequence of its activity on enzymes, particularly on those with -SH group. There are two basic clinical forms of the disease: liver disease or neurologic disease. Before puberty the liver damage is more frequent, while in adolescents and young adults neurologic form of the disease is usual. The liver disease is nonspecific and characterized by symptoms of cirrhosis and chronic aggressive hepatitis. The only specificity is hemolytic anemia which, in combination with previous symptoms, is important for diagnosis of the disease. Neurologic symptoms are the most frequent consequence of pathologic changes in the basal ganglia. In our patients the most frequent symptoms were tremor (63%); dysarthria, choreoathetosis and rigor (38%); ataxia and mental disorders (31%); dysphagia and dystonia (12%), diplopia, hypersalivation, nystagmus and Babinski's sign (6%). Among pathologic changes in other tissues and organs the most important is the finding of Kayser-Fleischer ring in the cornea as a result of copper accumulation. Its importance for precise diagnosis is great. The diagnosis of the disease is based on anamnesis, clinical examination, specific and nonspecific laboratory tests. The therapy of choice is penicillamine. If we use it early, the result will be good remission in the majority of patients. Late diagnosis or delay in treatment cause death which is the result of bleeding from esophageal varices or basal ganglia disease. Immunologic damages caused by penicillamine demand interruption of therapy and substitution by three-ethyl-tetra-amine (TETA). We also use zinc salts and tetratiomolibdate in therapy of this disease. Pathogenesis, clinical picture and therapy of the disease are based on our own results.
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PMID:[Hepatolenticular degeneration]. 226 49

A 12-year-old boy with Wilson's disease developed exertional dyspnea, cyanosis, and finger clubbing 10 months after diagnosis. The hypoxemia was caused by arteriovenous shunting, demonstrated by radionuclide scanning and pulmonary arteriography. Orthotopic liver transplantation was performed after the development of severe hypoxemia. There was no apparent reversal of the intrapulmonary arteriovenous shunting and he died 10 days posttransplantation of multiple organ failure secondary to hypoxemia. Monitoring arterial oxygen saturation in children with cirrhosis is warranted since the presence of significant arteriovenous shunting may influence prognosis and decisions regarding liver transplantation.
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PMID:Failure of liver transplantation in Wilson's disease with pulmonary arteriovenous shunting. 230 74

Diagnosis of Wilson's Disease in the early stages may be elusive in patients presenting without neurological symptoms. A case history is presented which demonstrates the pitfalls in making the diagnosis. Presenting psychiatric symptoms were nonspecific. Ceruloplasmin level was initially elevated to normal range. Liver biopsy showed early nonspecific cirrhosis; staining for copper did not show the dramatic effects expected with Wilson's Disease. Neurological examination, including NMR, was within normal limits. Kayser-Fleischer rings are no longer considered pathognomic. Urinary copper excretion helped to establish the diagnosis.
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PMID:Pitfalls of diagnosis in the early stages of Wilson's disease. 200 54

Brain-stem auditory evoked potentials (BAEPs) were studied in 69 patients with different types of hepatic diseases. BAEPs were normal in viral hepatitis, but the peak V and interpeak I-V latencies were prolonged in liver cirrhosis. Prolongation in peaks III, IV and V and interpeaks I-III, III-V and I-V were observed in both alcoholic liver disease and Wilson's disease with the latter more severely affected. The present data indicate that BAEPs may be used to study the effect of various hepatic diseases on the CNS.
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PMID:Brain-stem auditory evoked potentials in different types of hepatic diseases. 244 68

Copper granules in hepatocytes were examined by the p-dimethylaminobenzylidene rhodanine method in 965 liver biopsy specimens obtained from patients with various liver abnormalities other than Wilson's disease and biliary diseases. The granules were found in chronic active hepatitis (incidence of positive cases: 17.2%) and alcoholic fibrosis (22%) with lobular disarray and fibrosis, nonbiliary liver cirrhosis (28%), and drug-induced cholestasis (15%). Copper granules were present in the periportal or periseptal hepatocytes where the granules were mainly found in the perinuclear cytoplasm. These intracellular and intralobular distribution patterns of copper granules resembled those of primary biliary cirrhosis. These data suggest that hepatic fibrosis and lobular disarray with fibrosis in these chronic liver disease may lead to distortion or interruption of small biliary branches followed by disturbance of bile flow and deposition of copper granules. Copper stain seems to provide a valuable information for assessment of progression of these chronic liver diseases. Impaired biliary excretion seems important in deposition of copper granules in drug-induced cholestasis.
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PMID:Survey of copper granules in liver biopsy specimens from various liver abnormalities other than Wilson's disease and biliary diseases. 246 23

Eleven patients with newly diagnosed Wilson's disease were treated with zinc acetate as their sole anticopper therapy. Treatment duration was 8 to 37 months. Three of the patients had symptoms; in eight who were presymptomatic, diagnosis was made because of affected siblings who had symptoms. All patients did well clinically. Copper absorption was suppressed, as reflected by blockade of absorption of orally administered copper 64. Values for 24-hour urine copper and nonceruloplasmin plasma copper (freely available copper) were reduced. Values for liver-derived serum enzymes were also generally reduced in patients who had pretreatment elevations. Percutaneous liver biopsies were done initially and repeated in seven of the patients after 12 to 35 months of zinc therapy. In five of these patients a second biopsy specimen showed higher levels of copper than the first. In three of these five a third biopsy 6 to 23 months after the second revealed liver copper values that either had returned to the baseline value or were lower. One patient's initial biopsy specimen showed active inflammation, which subsided with therapy. All of the biopsies revealed histologic scarring typical of cirrhosis, and this did not appear to change over the course of therapy. We conclude that hepatic copper may increase temporarily during early zinc therapy but that the accumulated copper is sequestered in a nontoxic form. On the basis of animal studies we postulate that this sequestered copper is primarily bound to the high levels of hepatic metallothionein induced by zinc. Zinc appears to be a reasonable option for the initial treatment of patients with Wilson's disease, particularly those with presymptomatic disease.
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PMID:Treatment of Wilson's disease with zinc. VI. Initial treatment studies. 259 53


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