[Biomarkers of angiogenesis and endothelial dysfunction in children and adolescents with chronic viral hepatitis.]

At some works, it has been shown there are signs of damage and endothelium dysfunction in patients with chronic viral hepatitis (CVH) and liver cirrhosis of viral etiology the severity of these conditions depends on the severity of the pathological process. Evaluation of the role of angiogenic factors and endothelial dysfunction in persistent of CVH in children and adolescents. 35 patients were examined: of which 11 with chronic hepatitis B (CHB) and 24 with chronic hepatitis C (CHC). The reference group consisted of 120 practically healthy persons of the corresponding age and sex. VEGF-A, angiotensin (ANG), soluble receptors of VEGF-A (sVEGF-R1 и sVEGF-R2) and trombomodulin (TM) have been investigated in serum by enzyme immunoassay using special kits (BCM Diagnostics, USA). Other endothelial dysfunction markers as von Willebrand factor (vWf) was determined in blood plasma by immunoturbidimetry (Siemens, Germany), plasminogen (PLG) was investigated due to extended coagulation. In children with CVH, regardless of etiology, the concentration of VEGF-A was significantly lower, and sVEGF-R2, sVEGF-R1 and TM was higher than in children without liver disease (p <0.001, p <0.05, p <0.01, p <0.001, respectively). The concentration of TM and the level of PLG activity in patients with CHC were slightly higher than in CHB. Decreased level of VEGF-A and increased expression of its soluble receptors indicate enhanced inhibition of angiogenesis in CVH, which may indicate the pathogenetic role of this phenomenon in the development of liver damage in CHC.

[The non-invasive diagnostic of fibrosis and cirrhosis of liver under chronic viral hepatitis: publications review].

The chronic viral hepatitis is characterized by progressing course. In connection with this fact, there is a risk of development of fibrosis of liver. The diagnostic of this disease biopsy is applied as main technique. However, this invasive procedure is not always safe for patient. Therefore, it is applied only in specialized institutions, requires special training of medical personnel and has a number of contraindications. In recent years, in the capacity of noninvasive diagnostic of different stages of fibrosis of liver a number of serum markers are considered. Among them, the most number of studies concerns hyaluronic acid, collagen type IV, matrix metalloproteinase and their tissue inhibitors, transforming growth factor ß. The review presents actual information concerning possibilities of application of these serological indices in practical medicine in patients with chronic viral hepatitis.

[Current status of vascular remodeling and angiogenesis in chronic liver diseases].

The review focuses on the analysis of researches on the pathophysiology of liver vascular bed, mesenteric vessels, as well as the characteristics of angiogenesis in CLD. The results of this review shows that one of the most important areas of research is soluble vascular endothelial growth factor receptors, disclosing their importance for prognosis and treatment of diseases that occur with severe disorders of angiogenesis, including in CLD.

[The Relationship of the Degree of Impairment of the Structure and Function of the Liver with its Chronic Illnesses in Children].

OBJECTIVE: Our aim was to on the basis of determining the degree of violation of the structure and function of the liver establish their relationships and to assess the dynamics of liver disease in its chronic illnesses in children. METHODS: With the help of the developed scoring systems were used to assess the degree of liver dysfunction and the degree of disruption of the structure of the liver and the severity of portal hypertension. RESULTS: The results of the diagnostic methods 252 children aged 1 to 17 years (mean age of 11.8±3,5) with Wilson disease (WD), autoimmune hepatitis (AIH), chronic hepatitis C (CHC) were analyzed; 48 patients underwent liver transplantation. In children with WD, AIHand CHC liverfunction reduced by 41.3±12.9% to 28.8±12.5% and 19.1±7.8% respectively. Structure of the liver in children with WD, AIH and CHC was disturbed by 25.0±8.1% to 20.4±9.2% and 6.8±4.4% respectively. Thefunction and structure violations of the liver more pronounced in liver cirrhosis. The use of the developed scoring systems to monitor the severity of liver damage in the dynamics and evaluation of the effectiveness of the therapy is demonstrated. The degree of liver dysfunction is directly dependent on the degree of its structure. Abnormal liverfunction ≥40% and ≥40% of its structure with treatment failure can be used as a criterion of indicationsfor elective liver transplantation with its chronic diseases in children. CONCLUSION: Developed a point system to determine liver function and a point system to determine disruption of the structure of the liver and the severity of portal hypertension in children can serve as an objective criterion for assessing the severity of liver disease, monitoring their changes in the dynamics with the assessment of the effectiveness of the therapy and making decisions about the need for routine liver transplantation in its chronic illnesses in children.

[THE MODERN CONCEPTS OF HEMOSTASIS SYSTEM UNDER CHRONIC DISEASES OF LIVER: THE PUBLICATIONS REVIEW].

The disorder of system of hemostasis under chronic diseases of liver results in coagulation imbalance affecting both primary and secondary hemostasis. The shifting of hemostasis balance beyond the limits of physiological standards in such patients can result either in bleeding or thrombosis. For a long time already it is considered that in patients with chronic diseases of liver alterations in hemostasis system and occurrence of bleeding are very often interrelated. However results of such screening coagulation tests as prothrombin time and activated partial thromboplastin time poorly correlate with onset and duration of bleeding, for example after liver biopsy and also with occurrence of gastro-intestinal bleeding in patients with terminal stage of diseases of liver The foreign publications of last decade contest concept of cause and effect relationship between changes of indicators of screening coagulation tests and risk of development of bleeding in patients with chronic diseases of liver The publications also dispute both usefulness of the given tests in evaluation of hemorrhages and expediency of therapeutic strategies in the case of correction of anomalous results of mentioned tests. This issue in patients with rare diseases is factually unexplored. For example, there are single publications concerning patients with glycogenous disease type. The bleeding in such patients begin in early childhood They are related to dysfunction of thrombocytes and decreasing of particular oligomers of von Willebrand factor Hence, disorders in various chains of hemostasis system in patients with chronic diseases of liver are characterized by many unresolved issues that hinder furthering of development of diagnostic biomarkers. At that, diagnostic of coagulopathies and correction of pathological conditions in such patients the new tests are to be developed to monitor states of hemostasis system in patients with chronic diseases of liver, rare nosologic forms included.

[The experience of applying system of continuous monitoring of content of glucose in children with glycogen disease].

The sampling included 23 children with glycogen disease. All patients were examined using system of continuous monitoring of content of glucose applied during 72 hours. It was established that hypoglycemia was detected in 19 (82.6%) children. At that, in 7 (30.4%) children the level of glucose was below detected range (< 2.2 mmol/l). In patients ignoring proposed recommendations (lack of compliance) expression of hypoglycemia was reliably higher than in children being on a diet and following recommendations of physician. In primary patients as compared with secondary patients rate and duration of hypoglycemia in blood serum activity of aspartate aminotransferase also was reliably higher. Independently of all that, the more frequently hypoglycemia developed the more expressed hypoglycemia was. Therefore, continuous monitoring of content of glucose in intercellular fluid is an effective instrument for detecting degree of compensation of carbohydrate metabolism in patients with glycogen disease. The day continuous monitoring of level of glucose permits to provide the most complete picture of fluctuations of glycaemia during a day. The obtained data can be used as a basis for composing an optimal algorithm of diet therapy.

[DETERMINING THE DEGREE OF LIVER DYSFUNCTION IN CHILDREN WITH POSITIONS OF THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH (ICF)].

METHODS: Based on a retrospective analysis of biochemical blood parameters which characterize the role of liver function in the metabolism of proteins, fats and carbohydrates (considered indicators of ALT, AST, De Ritis coefficient, bilirubin, albumin, fibrinogen, prothrombin, transferrin, ceruloplasmin, cholesterol, urea, ammonia, glucose, lactate) in 95 children without liver pathology, 15 children who died of liver failure, 295 patients with various liver diseases who were treated in the SCCH, a scale system was developed as a support tool to assess liver dysfunction. RESULTS: Each biochemical indicator was assessed on a five-point scale. The level of a biochemical indicator, which corresponded to the absence of disorders, was estimated as 4 points, corresponding to "insignificant disorders"--as 3 points, "moderate disorders"--as 2 points, "severe disorders"--as 1 point, "absolute disorders"--as 0 points. The total score is the estimate of the degree of liver dysfunction. According to the recommendations of the International Classification of Functioning, Limitations of vital activities and Health, the decrease of the number of points on 0-4% (54-56 points) corresponds to the absence of the liver dysfunction, on 5-24% (43-53 points)--insignificant disorders of liver function, on 25-49% (29-42 points)--moderate hepatic impairment, on 50-95% (3-28 points)--severe disturbances of liver function, on 96-100% (0-2 points)--absolute dysfunction of the liver. CONCLUSIONS: A scoring system of assessing liver dysfunction can be applied at any stage of the examination and treatment of children of any age, as used in biochemical parameters do not depend on the age of the patient. It is an objective criterion for assessing the degree of liver dysfunction and can be used to assess the severity of the pathological process in the dynamics determining the prognosis of the disease and can be the criterion of the indications for liver transplantation, and also used during the of medico-social expert examination.

[DETERMINING THE DEGREE OF DISRUPTION OF THE STRUCTURE OF THE LIVER AND THE SEVERITY OF PORTAL HYPERTENSION IN CHILDREN].

AIM: To develop a system to define the degree of liver disruption and severity of portal hypertension in children based on the International Classification of Functioning, Disability and Health (ICF). PATIENTS AND METHODS: Studied the results of laboratory and instrumental methods 382 children: 267 patients with various liver diseases, including 49 patients who underwent liver transplantation, and 115 children without liver disease. RESULTS: Based on analysis of statistical data obtained were identified 10 indicators, a set of changes which can be used to assess the degree of disruption of the structure of the liver and the severity of portal hypertension: indicators that reflect the severity of fibrosis and cirrhosis of the liver (METAVIR score on a scale at fibroelastometrii, scores are Desmet at morphological study of the liver) and indicators that reflect the severity of portal hypertension (the diameter of the portal vein, splenic vein diameter, the length of the spleen, recanalization of the umbilical vein, esophageal varices, ascites, hydropericardium, hydrothorax). Each of the indicators was assessed on a 5-point system. Number of points reflects the sum of the changes of these parameters. Decrease the number of points on 0-4% (38-40 points) is regarded as a lack of structural failure of the liver and the severity of portal hypertension by 5-24% (30-37 points)--minor violations on 25-49% (20-29 points) -moderation disorders, 50-95% (3-12 points)--severe handicaps, 96-100% (0-2 points)--absolute violation. Studied the dynamics of children with autoimmune hepatitis, Wilson's disease and chronic hepatitis C. CONCLUSION: The proposed scoring system for assessing the degree of disruption of the structure of the liver and the severity of portal hypertension can be used as an objective criterion of the severity of the pathological process, to estimate the dynamics of defeat against the background of the therapy, determining the prognosis of the disease and as a criterion of the indications for liver transplantation.

[Mitochondrial dysfunction in children with hepatic forms of glycogen storage disease].

AIM: The purpose of the study was to assess mitochondrial dysfunction severity in patients with hepatic forms of glycogen storage disease (GSD). PATIENTS AND METHODS: We examined 53 children with GSD in the dynamics. Distribution of children by disease types was: 1st group--children with GSD type I, 2nd group--children with GSD type III, 3rd group--children with GSD type VI and IX; comparison group consisted of 34 healthy children. Intracellular dehydrogenases activity: succinate dehydrogenase (SDH), glycerol-3-phosphate-dehydrogenase (GPDH). nicotinamideadenin-H-dehydrogenase (NADH-D) and lactatdehydrogenase (LDH) was measured using the quantitative cytochemical method in the peripheral lymphocytes. RESULTS: It was revealed decrease of SDH- (p < 0.001) and GPDH-activities (p < 0.001), along with increase of the NADH-D activity (p < 0.05) in all patients with GSD, (SDH/ NADH-D) index was decreased (p < 0.001). LDH activity was increased in groups 1 (p < 0.05) and 3 (p < 0.01), compared with comparison group. The most pronounced intracellular enzymes activity deviations were observed in children with GSD type I, that correspond to more severe clinical form of GSD. It was found strong correlation between intracellular enzymes activity and both hepatomegaly level (R = 0.867) and metabolic acidosis severity (R = 0.987). CONCLUSION: Our investigation revealed features of mitochondrial dysfunction in children with GSD, depending on the GSD type. Activities of lymphocytes enzymes correlates with the main disease severity parameters and can be used as an additional diagnostic criteria in children with hepatic form of GSD.

[History case of multiple hepatic adenomas in adolescent with severe course of glycogen storage disease type lb].

We represented a case history of multiple hepatic adenomas in an adolescent with severe clinical course of glycogen storage disease type lb (compound heterozygous mutations c.1042_1043delCT and c.817G>A in the SLC37A4). The patient was prescribed a raw cornstarch and hepatoprotectors therapy, but he and his parents had low compliance to treatment. At the age of 13,5 years ultrasound investigation and computed tomography revealed multiple adenomas. Due to the severe condition of the patient it was impossible to perform focal hepatic biopsy. At present time the patient receives treatment focused on correction of metabolic disturbances, thereafter an applicability of exploratory puncture will be settled for the further patient surveillance. The modern data on causes and risk factors of hepatic adenomas in such patients, the possibility of their malignization, the algorithm of the follow-up and the methods of treatment are presented in the discussion.

[Potentialities of non-invasive diagnosis of liver cirrhosis in children with the use of serological markers].

The study included 95 children with chronic hepatic disorders of different etiology. All of them underwent hepatic puncture biopsy for morphological studies and calculation of histological sclerosis index based on the Knoddel scale. Commercial enzyme immunoassay kits were used to measure hyaluronic acid (HA), type IV collagen (CIV), matrix metalloproteinase-1 (MMP-2), transforming growth factor-beta 1 (TGF), and leptin levels as non-invasive markers of fibrosis. It was shown that concentrations of TGF and MMP-2 at early stages of hepatic fibrosis, HA and CIV at its later stages are of diagnostic value.