[Evaluating the efficacy of diet therapy with protein component modification at Wilson disease].

Wilson disease (WD) is a rare hereditary disorder of copper metabolism, based on of the ATP7B gene mutation, resulting in defect of cooper excretion, which leads to accumulation of cooper in tissues and internal organs (especially in the liver and brain). The basic principle of diet therapy for patients with WD is a diet with reduced copper content, adherence to which is accompanied by significant dietary restrictions, so patients with WD, compared to other liver diseases, represent the most difficult contingent for adjustment of diet. The aim: to assess of the effect of diet therapy with modification of the protein component on nutritional status of patients with WD. Material and methods. The study included 33 patients (15 men and 18 women, 31.4±10.2 years old) with WD. All patients had liver damage: non-cirrhotic stages (NCC) - in 12 (36.3%) patients, liver cirrhosis (LC) - in 21 (63.7%) patients. Out of the last, 14 (66.7%) patients had compensated LC, 7 (33.3%) patients had decompensated LC. The average age of the patients. All patients were divided into two groups, comparable by body mass index. For 2 months outpatients of the 1st group (n=17) received a specialized diet with a modification of the protein component, made by incorporating 20 g of dry composite protein mix (containing 50% protein in the form of milk protein concentrate, 4% dietary fiber) into the daily diet. Outpatients of the 2nd group (n=16) received the same diet without modification. All patients were provided anthropometry, including shoulder circumference and triceps skin-fold measurement, and analysis of the body mass composition with bioimpedance analyzer, the index of lean mass was additionally calculated. Clinical and biochemical blood tests were also conducted for all patients. Results and discussion. As a result of the diet therapy, statistically significant (p<0.05) changes were observed in patients of the 1st group who received a diet with a modification of the protein component: an increase in the index of lean mass (by 3.0%) and circumference of the shoulder muscles (by 2.3%), serum total protein and albumin (by 7.9 and 6.1%), an increase in the absolute number of lymphocytes (by 18.8%) and decrease in serum total bilirubin (by 20.2%). A statistically significant decrease in the level of free copper was observed in both groups (by 2.1 and 1.8 fold). Conclusion. The use of a specialized diet with a modification of the protein component, based on the inclusion of a protein composite dry mix in the diet, improves the nutritional status indicators in patients with Wilson disease.

[The new aspects of clinical nutrition at Wilson disease: actuality and perspectives].

Wilson disease is hereditary disorder of copper metabolism, based on defect of cooper excretion, which leads to accumulation of cooper in the liver and brain. This disease is one of the most difficult to diagnose. Without treatment disease brings to early disability and lethal outcome. In the article, domestic and foreign approaches to dietary management of Wilson disease have been compared. Diet is not recommended as sole therapy. The degree of restriction of the products containing copper now is discussed. According to the Russian clinical guidelines of diagnosis and treatment of Wilson disease exception of products, copper content in which exceeds 0.5 mg/100 g (liver, shellfish, nuts, cocoa products, mushrooms, bean and some grains) is recommended, while in EASL clinical guidelines there are no any information about restriction of the products containing copper. It is necessary to pay attention not only to cooper restriction, but also to qualitative components of diet. Protein is important part of nutrition under liver disease. According to ESPEN guidelines, the recommended protein intake at chronic hepatitis and cirrhosis is 1.2-1.5 g/kg/day. Dairy products and whey protein are good sources of protein, they almost do not contain cooper, therefore they can be used without restrictions at Wilson disease (in case of normal lactose and milk protein tolerance). The reduce of consumption of sugar, refined carbohydrates and trans fats is also recommended. Dietary recommendations must take into consideration the nutrition status of the patient (protein energy malnutrition, normal body weight, obesity) and degree of liver damage (chronic hepatitis, cirrhosis). It is necessary to develop individualization of diet, increasing efficiency of medicinal treatment of Wilson disease.

Dietary copper restriction in Wilson's disease.

Dietary copper restriction has long been considered an important aspect of treatment for Wilson's disease (WD). However, evidence supporting this approach is limited. There are no published randomised controlled trials examining this recommendation due to rarity of the disease and variable presentation. This review summarises current knowledge on the absorption and regulation of copper in humans and its relevance to patients with WD. Studies have demonstrated that as the level of dietary copper increases, the proportion absorbed decreases. This observation implies that 'high copper' foods that WD patients are generally advised to avoid would need to be consumed in large amounts to impact markedly on the quantity absorbed. Dietary copper restriction is unlikely to reduce the amount absorbed significantly and is not only difficult to manage but restricts food groups unnecessarily, detracting from the provision of substrates essential for improving nutritional status in a nutritionally compromised group. Medical management for WD is effective in compliant patients, allowing stabilisation of the liver disease. Based on current evidence, dietary copper restrictions in stable WD patients who are adherent to medical therapy are unnecessary with two food exceptions (shellfish and liver).

Wilson's disease: clinical, genetic and pharmacological findings.

Wilson's disease (WD) is an autosomal recessive disorder characterized by copper accumulation and toxicity in the liver and in other tissues. WD presents with liver disease, neurological or psychiatric disturbances or other less common clinical features. Diagnosis of WD is often difficult and may be formulated through clinical, biochemical, imaging, histochemical and genetic evaluations. Pharmacological approach in WD consists in copper chelating agents such as D-penicillamine, trientine, dimercaprol and tetrathiomolybdate. In 1997 zinc was approved for maintenance therapy of WD by the U.S. FDA. Orthotopic Liver Transplantation is indicated in fulminant hepatic failure, progressive hepatic insufficiency despite therapy, cirrhosis with complications of portal hypertension. However the most appropriate therapy, including OLT, remains controversial in WD and further studies are needed especially in order to differentiate the possibility of specific therapies for different WD phenotypes.

Diagnostic dilemmas of Wilson's disease: diagnosis and treatment.

Wilson's disease, an autosomal recessive disorder of copper metabolism, may defy diagnosis in children. The classical triad of Kayser-Fleischer rings, neurologic dysfunction, and hypoceruloplasminemia may be absent. Patients may be seen initially with acute or chronic hepatitis, hemolytic anemia, or neurologic dysfunction. Guidelines are presented for diagnosis of Wilson's disease based on a review of 25 pediatric and adolescent patients. A high index of suspicion in necessary so that therapy with penicillamine may be begun before irreversible liver or neurologic damage occurs. The prognosis is excellent when diagnosis and treatment are established early.

[Diet therapy in acute and chronic liver diseases]. / Ernährungstherapie bei akuten und chronischen Lebererkrankungen.

Nutrition is an essential part of the therapy of patients with acute and chronic liver diseases. Special recommendations are given for patients with ascites, hepatorenal syndrome, encephalopathy, liver failure and secondary diabetes. Nutrition is an essential treatment in patients with hepatic encephalopathy. In acute liver failure, parenteral nutrition is basic for the restoration of homeostasis. This article provides detailed recommendations for nutrient supply for patients with acute and chronic liver diseases.

[Changes in zinc metabolism during long-term D-penicillamine treatment of patients with Wilson-Konovalov disease]. / Izmenenie obmena tsinka na fone dlitel'nogo lecheniia D-penitsillaminom u bol'nykh bolezn'iu Vil'sona--Konovalova.

Using atomic absorption spectrophotometry, the authots determined zink levels (in correlation with the time-course of copper elimination) in the blood serum and urine of 28 patients with hepatocerebral dystrophy prior to and during the first year of D-penicillamine treatment and in 55 patients who had been on this therapy for a number of years. The zink concentration in the patients' blood serum prior to treatment tended to decline. Such a decrease was also noted in cirrhosis of other etiologies. Thiol therapy resulted in a gradual increase in the urine zink elimination which followed a pattern of the drug dose increment and could be two to three times higher than normal in cases of prolonged treatment. Nevertheless, these patients exhibited no symptoms of zink insufficiency and the zink concentration in the blood serum had been normal for a number of years, which may be explained by an enhanced absorption of zink from the intestines and by its mobilization from the tissue depots. The pathological manifestations observed in six patients with the asthenoneurotic syndrome regressed following zink administration.

Medical management of chronic liver diseases in children (part I): focus on curable or potentially curable diseases.

The management of children with chronic liver disease (CLD) mandates a multidisciplinary approach. CLDs can be classified into 'potentially' curable, treatable non-curable, and end-stage diseases. Goals pertaining to the management of CLDs can be divided into prevention or minimization of progressive liver damage in curable CLD by treating the primary cause; prevention or control of complications in treatable CLD; and prediction of the outcome in end-stage CLD in order to deliver definitive therapy by surgical procedures, including liver transplantation. Curative, specific therapies aimed at the primary causes of CLDs are, if possible, best considered by a pediatric hepatologist. Medical management of CLDs in children will be reviewed in two parts, with part I (this article) specifically focusing on 'potentially' curable CLDs. Dietary modification is the cornerstone of management for galactosemia, hereditary fructose intolerance, and certain glycogen storage diseases, as well as non-alcoholic steatohepatitis. It is also essential in tyrosinemia, in addition to nitisinone [2-(nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione] therapy, as well as in Wilson disease along with copper-chelating agents such as D-penicillamine, triethylenetetramine dihydrochloride, and ammonium tetrathiomolybdate. Zinc and antioxidants are adjuvant drugs in Wilson disease. New advances in chronic viral hepatitis have been made with the advent of oral antivirals. In children, currently available drugs for the treatment of chronic hepatitis B virus infection are standard interferon (IFN)-α-2, pegylated IFN-α-2 (PG-IFN), and lamivudine. In adults, adefovir and entecavir have also been licensed, whereas telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine, and thymosin α-1 are currently undergoing clinical testing. For chronic hepatitis C virus infection, the most accepted treatment is PG-IFN plus ribavirin. Corticosteroids, with or without azathioprine, remain the basic strategy for inducing remission in autoimmune hepatitis. Ciclosporin (cyclosporine) and other immune suppressants may be used for patients who do not achieve remission, or who have significant side effects, with corticosteroid/azathioprine therapy. The above therapies can prevent, or at least minimize, progression of liver damage, particularly if started early, leading to an almost normal quality of life in affected children.

Doença de Wilson (degeneração hepatolenticular): revisão bibliográfica e relato de caso / Wilson’s disease (hepatolenticular degeneration): revision and case report

Este estudo faz, inicialmente, revisão dos aspectos mais atuais referentes a conceito, quadro clínico, diagnóstico e tratamento do distúrbio metabólico do cobre, definido como doença de Wilson. E relata o caso clínico de um jovem acometido de uma sequência de sintomas superpostos de origem gastrintestinal, neurológico e psiquiátrico. Pela multiplicidade e gravidade dos sintomas, teve o diagnóstico final de transtorno psicótico agudo polimórfico, com intensa inibição psicomotora. A partir de uma análise integrada dos exames já solicitados, suspeitou-se de um distúrbio metabólico de origem hereditária ou adquirida que justificasse simultaneamente os sintomas. O distúrbio da excreção do cobre, doença de Wilson, veio justificar toda a sintomatologia referida e foi confirmado a partir da dosagem sanguínea baixa de ceruloplasmina e da presença dos anéis de Kaiser-Fleischer na córnea do paciente.

It will be initially revised by the authors the most actual aspects of the concept, clinical situation, diagnosis and treatment concerning to a metabolic disturbance of the copper, Wilson?s disease. Afterwards it will be described the clinical case of a young man attacked of a sequence of superposed symptoms of gastrintestinal, neurological and psychiatric origin. For the multiplicity and gravity of the symptoms acute polimórfico with intense psicomotora inhibition had the final diagnosis of "psychotic Upheaval". Starting from an integrated analysis of the exams, it was suspected about a metabolic disturbance of hereditary or acquired origin that justify all the symptoms simultaneously. The disturbance of the excretion of copper, Wilson's disease, came to justify all the referred symptomatology and it was confirmed by the decrease sanguine dosage of ceruloplasmin, the presence of rings of Kayser-Fleischer in the córnea of the patient and of neurological lesion at the magnetic nuclear ressonance. The diagnosis of Wilson's disease in patients with simultaneous digestive (hepática cirrhosis), neurological and inexplicable psychiatric disturbances will always have to be faneed because the precocious treatment will mainly prevent serious and permanent organic damages for the liver and brain. The specific treatment was initiated and the maintenance of exactly has provoked significant improvements and a gradual new outbreak of the symptoms reintegrating the patient the family and the society.

Successful pregnancy in Wilson's disease: a case report and review of the literature.

Pregnancy in patients with Wilson's disease can be successfully managed. A case of successful pregnancy in a patient with Wilson's disease is presented. The pathophysiology, protean clinical manifestations and treatment modalities are described.

Effects of anticopper therapy on hepatocellular mitochondria in patients with Wilson's disease: an ultrastructural and stereological study.

Liver biopsy specimens from 7 patients with Wilson's disease (hepatolenticular degeneration), obtained before and after 3 to 5 years of D-penicillamine therapy, were studied by electron microscopy and stereology. The characteristic mitochondrial abnormalities encountered in the hepatocytes of untreated patients were less pronounced or disappeared after treatment in 5 of the 7 patients. Simultaneously, relative mitochondrial volume, surface density of the external mitochondrial membranes, and the number of these profiles per unit area increased, whereas abnormal elevations SGOT and SGPT returned to normal levels.

Usefulness of Scheimpflug photography to follow up Wilson's disease.

A 24-year old female with ocular changes (Kayser-Fleischer ring and sunflower cataract) indicating Wilson's disease was followed up from 9 years of age with anterior eye segment image documentation by Scheimpflug photography. A low copper diet and systemic D-penicillamine were administered after the initial diagnosis of Wilson's disease. During a 15-year follow-up period, the yellowish/brown-colored granular opacification on the anterior lens capsule and/or in the capsule has mostly disappeared and instead, the same type of opacification has emerged on the posterior lens capsule, showing rather progressive changes compared with the initial findings. These changes which had developed in the lens during the past 15 years were difficult to detect by slit lamp examination alone, but they were clearly revealed by Scheimpflug slit images. To our knowledge this is the first case report on ocular changes disclosed through the application of a newly developed anterior eye segment examination. Ergo, Scheimpflug photography is valuable for follow-up studies of ocular complications seen in patients with Wilson's disease.

Does a vegetarian diet control Wilson's disease?

The literature indicates that copper (Cu) is less bioavailable from a vegetarian as compared to mixed diet. Further, several groups, including ours, find rather marginal average Cu intake in the typical American diet. For example, our data indicate that Wilson's disease patients on a typical American diet ingest only about 25% more Cu than is required. This suggests that a vegetarian diet, if it reduced bioavailability by about 25% or more, would be an adequate maintenance therapy for Wilson's disease. Observations in two of our patients, who were on lactovegetarian diets by choice, and who were almost totally noncompliant with anti-Cu therapy, support this view. These observations suggest that vegetarian diets may be a management tool for Wilson's disease. They also further emphasize the marginal Cu intake in American diets, and suggest that some seemingly healthy people, particularly vegetarians, may be at risk for mild Cu deficiency.