Hepatobiliary malignancies in Wilson disease

Pfeiffenberger, Jan; Mogler, Carolin; Gotthardt, Daniel; Schulze‐Bergkamen, Henning; Litwin, Tomasz; Reuner, Ulrike; Hefter, Harald; Hüster, Dominik; Schemmer, Peter; Członkowska, Anna; Schirmacher, Peter; Stremmel, Wolfgang; Cassiman, David; Weiss, Karl Heinz

doi:10.1111/liv.12727

Cited by 86 publications

(55 citation statements)

References 38 publications

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“…Wilson's disease is an autosomal recessive hereditary disorder because of mutations in the Wilson disease (ATP7B) gene and is characterized by copper accumulation in several tissues, primarily liver, brain and other vital organs . A recent cohort study on 1186 patients showed that sporadic cases of iCCA (0.5%) occurred in patients with Wilson's disease . The reason for these low incidences is still debated.…”

Section: Risk Factorsmentioning

confidence: 99%

Cholangiocarcinoma: Epidemiology and risk factors

Khan

Tavolari

Brandi

2019

Liver International

507

495

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Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host‐specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co‐occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide.

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Section: Risk Factorsmentioning

confidence: 99%

Cholangiocarcinoma: Epidemiology and risk factors

Khan

Tavolari

Brandi

2019

Liver International

507

495

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“…The risk of a hepatoma developing in this situation is low, at 1 in 400 lifelong, but recent studies would suggest hepatocellular carcinoma is more common in Wilson's disease than appreciated. [88][89][90] Some authors do not advocate routine hepatoma surveillance in cirrhosis related to Wilson's disease. 8,91 In practice however, clinicians will often opt for hepatoma surveillance, especially in the elderly.…”

Section: Initial Therapymentioning

confidence: 99%

Insights into the management of Wilson’s disease

Kathawala

Hirschfield

2017

Therap Adv Gastroenterol

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Abstract:Wilson's disease is a rare, inherited autosomal recessive disease of copper metabolism, in which the causative gene, ATP7B, results in absent or reduced function of the ATP7B transporter important for biliary excretion of copper and incorporation of copper into caeruloplasmin. Affected patients accumulate excessive copper within the liver, brain and other tissues. A disease mainly of children, adolescents and young adults; clinical features vary from the asymptomatic state to chronic liver disease, acute liver failure, and neuropsychiatric manifestations. Diagnosis requires a high index of suspicion and is based on a combination of clinical signs, biochemical tests, hepatic copper content assay and mutation analysis of the ATP7B gene; to date, there are more than 500 mutations of ATP7B in patients with Wilson's disease. Early recognition and treatment can result in an excellent prognosis whereas untreated disease is almost always fatal. Drug therapies include chelating agents, such as penicillamine or trientine, and zinc salts. Liver transplantation is curative correcting the underlying pathophysiology and is traditionally indicated in acute liver failure or end-stage liver disease refractory to medical therapy. This review provides an overview of various aspects of Wilson's disease including molecular basis of the disease, clinical features, diagnostic and management strategies with their current limitations.

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“…Other features of the LEC rat limiting its use in modelling WD include the frequent occurrence of hepatocellular and cholangiocarcinoma. This is not concordant with human disease, in which progression of liver damage to carcinoma occurs in only 1.2% of patients (Pfeiffenberger et al 2015). Also unlike human disease, Kayser-Fleischer rings are absent in the LEC rat (Li et al 1991).…”

Section: Limitationsmentioning

confidence: 69%

“…This is not concordant with human disease, in which progression of liver damage to carcinoma occurs in only 1.2% of patients (Pfeiffenberger et al . ). Also unlike human disease, Kayser–Fleischer rings are absent in the LEC rat (Li et al .…”

Section: Rodent Modelsmentioning

confidence: 97%

Animal models of Wilson disease

Reed

Lutsenko²,

Bandmann

2018

Journal of Neurochemistry

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Wilson disease (WD) is an autosomal recessive disorder of copper metabolism manifesting with hepatic, neurological and psychiatric symptoms. The limitations of the currently available therapy for WD (particularly in the management of neuropsychiatric disease), together with our limited understanding of key aspects of this illness (e.g. neurological vs. hepatic presentation) justify the ongoing need to study WD in suitable animal models. Four animal models of WD have been established: the Long-Evans Cinnamon rat, the toxic-milk mouse, the Atp7b knockout mouse and the Labrador retriever. The existing models of WD all show good similarity to human hepatic WD and have been helpful in developing an improved understanding of the human disease. As mammals, the mouse, rat and canine models also benefit from high homology to the human genome. However, important differences exist between these mammalian models and human disease, particularly the absence of a convincing neurological phenotype. This review will first provide an overview of our current knowledge of the orthologous genes encoding ATP7B and the closely related ATP7A protein in C. elegans, Drosophila and zebrafish (Danio rerio) and then summarise key characteristics of rodent and larger mammalian models of ATP7B-deficiency.

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Hepatobiliary malignancies in Wilson disease

Cited by 86 publications

References 38 publications

Cholangiocarcinoma: Epidemiology and risk factors

Cholangiocarcinoma: Epidemiology and risk factors

Insights into the management of Wilson’s disease

Animal models of Wilson disease

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