Defective biliary excretion of copper in Wilson's disease

Frommer, D.

doi:10.1136/gut.15.2.125

Cited by 113 publications

(34 citation statements)

References 27 publications

(20 reference statements)

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“…[1][2][3][4][5][6][22][23][24] This leads to the toxic accumulation of copper in the liver and other organs, such as the brain, kidneys, and corneas. Medical therapy with chelating agents has proven effective in controlling the disease progression and is effective in the prevention of central nervous system complications.…”

Section: Discussionmentioning

confidence: 99%

“…[26][27][28] Under these circumstances, liver transplantation appears to be the treatment of choice, with correction of the complications of liver failure and acceptable longterm outcomes. Since the first successful liver transplantation for Wilson' s disease in 1969, 29 a number of reports have been accumulated in the literature, addressing the role of transplantation in survival and reversibility of biochemical, 10,19,30 radiological, [20][21][22][23][24][25][26][27][28][29][30][31] and neurological 14,19,32 manifestations of the disease. Nonimmune hemolysis is well Liver Transplantation for Wilson' s Disease described in patients with fulminant Wilson' s disease.…”

Section: Discussionmentioning

confidence: 99%

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Liver transplantation for wilson's disease: A single-center experience

Eghtesad¹,

Nezakatgoo²,

Jabbour³

et al. 1999

Liver Transpl

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Liver transplantation for wilson's disease: A single-center experience

Eghtesad¹,

Nezakatgoo²,

Jabbour³

et al. 1999

Liver Transpl

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“…[2][3][4] Homozygosity or compound heterozygosity for defects in this gene lead to a failure of the liver to excrete copper in the bile destined for loss in the stool. [5][6][7][8] This excretion is necessary to maintain a neutral copper balance. An epistatic effect of this genetic defect is usually a low blood ceruloplasmin.…”

mentioning

confidence: 99%

Treatment of Wilson's disease with zinc. XVII: Treatment during pregnancy

et al. 2000

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Therapy of Wilson's disease continues to evolve. In 1997, zinc acetate was added to the list of drugs approved by the Food and Drug Administration, which includes penicillamine and trientine. The mechanism of zinc's anticopper action is unique. It induces intestinal cell metallothionein, which binds copper and prevents its transfer into blood. As intestinal cells die and slough, the contained copper is eliminated in the stool. Thus, zinc prevents the intestinal absorption of copper. It is universally agreed that pregnant Wilson's disease patients should remain on anticopper therapy during pregnancy. There are numerous reports of such patients stopping penicillamine therapy to protect their fetus from teratogenicity, only to undergo serious deterioration and even death from renewed copper toxicity. Penicillamine and trientine have teratogenic effects in animals, and penicillamine has known teratogenic effects in humans. In this report we discuss the results of 26 pregnancies in 19 women who were on zinc therapy throughout their pregnancy. The evidence is good that zinc protects the health of the mother during pregnancy. Fetal outcomes were generally quite good, although one baby had a surgically correctable heart defect and one had microcephaly. (HEPATOLOGY 2000;31:364-370.)

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“…From these data, it seems reasonable to assume that increased biliary output in exogenous copper overload is a consequence of increased hepatic copper accumulation, while decreased biliary excretion of copper by impaired lysosomal exocytosis per se is responsible, at least in part, for the endogenous hepatic copper accumulation in LEC rats. Similarly, increased activities of hepatic lysosomal enzymes and decreased biliary excretion of copper have been found in patients with Wilson's disease (Goldfischer 1963;Frommer 1974) and impaired biliary excretion of copper into bile via hepatocyte lysosomes has been hypothesized as a pathogenesis of Wilson's disease (Sternlieb et al 1973). Taken together, LEC rats may serve as an excellent model to investigate the copper metabolism in spontaneous copper overload including Wilson's disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact pathogenesis remains unknown, impaired biliary excretion of copper via hepatocyte lysosomes has been postulated as a central defect in Wilson's disease (Sternlieb et al 1973). However, information regarding the actual alteration of the "lysosome-to-bile hepatic excretory pathway (LaRusso 1989; Yamazaki and LaRusso 1989)" in spontaneous copper accumulation is fragmentary (Goldfischer 1963;Frommer 1974). Furthermore, previous experimental studies (Gross et al 1989; Harada et al 1993), investigating the relationship between biliary copper excretion and lysosomal exocytosis, equivocally used animals exogenously overloaded with copper which may potentially differ from spontaneous copper overload.…”

mentioning

confidence: 99%