[Liver transplantations in children using reduced grafts]. / Transplantace jater u detí redukovaným stepem.

AIM: Liver transplantation is a life-saving procedure in patients with end stage liver disease. Five-year survival in patients indicated for transplantation based on standard indication criteria, has reached a rate over 80%. Shortage of suitable grafts remains the main problem in these procedures. While the situation in adult patients is relatively satisfactory, liver transplantations in children, mainly in the low-weight categories, remain a worldwide problem because of the absolute lack of suitable donors. In order to reduce mortality in the youngest patients on the waiting list, a concept of reduction of the adult graft for pediatric use was introduced in the early 1990s. Recent introduction of novel methods, such as split transplantations or transplantations between relatives, has resulted in lower mortality rates in the youngest recipients on the waiting lists. The author assesses a group of patients below 18 years of age, who underwent reduced liver graft transplantations in the Czech Republic. MATERIAL AND METHODS: From 1995 to 2009, a total of 43 patients below 18 years of age underwent transplantations, using 48 liver grafts. Further 17 children were sent abroad for transplantations, where a total of 23 liver grafts were used. Only patients who underwent transplantations using the liver grafts adjusted in IKEM were assessed in the patient group, i.e. 14 patients, resp. 16 liver grafts. Reduction was performed in 13 subjects. One subjects underwent transplantation between relatives and a liver split was used in two subjects. In the lowest weight category up to 10 kgs, 5 liver reductions were performed. OUTCOMES: Out of the total (n = 16), 4 grafts failed (2 were early postoperative failures, ie. within 2 postoperative days and 2 grafts failed in Month 5). The mean graft survival was 65 months. Within the youngest recipient age group (n = 5), no graft failure was recorded. The mean survival time is 26 months. CONCLUSION: Since 2007, the Czech Republic has been providing a program for all patients, including the lowest weight-category pediatric patients. To date data are satisfactory. No graft failure has been recorded in the category of the smallest (up to 10 kgs) pediatric patients.

Diagnostic efficacy of ERCP in cholestatic infants and neonates--a retrospective study on a large series.

BACKGROUND AND STUDY AIMS: Cholestatic jaundice in infants is a serious condition, requiring timely and accurate diagnostic evaluation. Our aim was to determine the safety and diagnostic efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of cholestatic liver disease in neonates and infants. PATIENTS AND METHODS: ERCP procedures in cholestatic infants performed in our endoscopy unit between December 1998 and March 2008 were reviewed retrospectively (n = 104 children, 48 boys, 56 girls; mean age 7 weeks, range 3 - 25 weeks; mean weight 4.05 kg, range 1.5 - 4.8 kg). Endoscopic findings were compared with final diagnoses. Statistical analysis was performed and sensitivity, specificity, positive (PPV) and negative (NPV) predictive values of ERCP were calculated both separately for each diagnosis and on aggregate. RESULTS: Cannulation of the papilla was successful in 95 of 104 patients (success rate 91.3 %). Biliary atresia of any type was found in 51 children (53.7 %), with a sensitivity of 86 %, a specificity of 94 %, a PPV of 96 %, and a NPV of 100 %. Choledochal cysts were found in seven children (7.4 %), with a sensitivity of 100 %, a specificity of 90 %, PPV of 86 %, and NPV of 100 %. Biliary stones were found in seven patients (7.4 %). Other structural pathology was found in six patients, and no abnormality was seen in 24 patients. No severe complications occurred during or after ERCP. CONCLUSIONS: ERCP in cholestatic infants, when performed in an expert center, is a safe and reliable procedure that can detect biliary tract abnormalities (e. g. biliary atresia, bile duct stones or choledochal cysts) with high sensitivity and specificity. Laparotomies can be prevented in infants by demonstrating normal patency of the biliary tract by ERCP or by magnetic resonance cholangiography if improvements in this technique are made.

Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs.

Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR = 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR = 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR = 2.9, 95% CI 1.5-5.7) and p.R702W (OR = 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.-308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.

[Living relative donor for liver transplantation in paediatric recipient]. / Transplantace jater dítete od zivého príbuzenského dárce.

Paper refers the first in Czech Republic liver transplantation in a child with the donor being the close living relative - the father. Indication was the chronic liver failure caused by biliary atresia after the Kasai procedures, which enabled the child to survive two years. Liver segments II. -III were transplanted with favourable postoperative development. Within the following twenty months the nutrition status and the psychomotor development of the child significantly improved. Authors discuss present situation and results of the paediatric liver transplantation in the world.

[HLA-DRB1/DQA1/DQB1 alleles and haplotypes in Czech children with celiac sprue]. / HLA-DRB1/DQA1/DQB1 alely a haplotypy ceských deti s celiakální sprue.

BACKGROUND: The celiac disease (CD) is a multifactor disease resulting from a life time abnormal immune response to gluten accompanied by autoimmune characteristics, which can in sensitive individuals evoke small bowel mucosa morphologic changes. The genetically sensitive individual to CD has not been defined yet, it is obvious, however, that this illness is closely linked to the HLA class II genes. The objective of our study was to detect associations of HLA class II alleles and haplotypes DRB1/DQA1/DQB1 in Czech CD children. METHODS AND RESULTS: A group of Czech CD children diagnosed according to ESPGHAN criteria was genotyped HLA for alleles of DRB1/DQA1/DQB1 loci. Genotyping of the HLA-DRB1/DQB1 haplotypes proved statistically significant association CD with haplotypes and alleles of this genetic system. 92.9% of patients have in their HLA phenotype allele DQA1*0501 in either cis or trans configuration with the DQB1 allele *0201/*0202. The extended HLA haplotype DRB*0301/DQA1*0501/DRB1*0201 as well as the haplotype DRB1*0701/DQA1*0201/DQB1*0202, are presented in 63.6% or in 61.0% CD patients respectively. The individual HLA class II alleles DRB*0301, *0701, DQA1*0201, *0501, DQB1*0201, *0202 and the above mentioned HLA haplotypes inclusively provide genotypic frequencies significantly different from healthy Czech individuals (P < or = 0.06 +/- 0.001). These results support the opinion that the HLA molecule expressed on the cellular surface as a alpha beta heterodimer encoded by the DQA1*0501 and DQB1*0201/02 alleles in either cis or trans configuration is responsible for the primary sensitivity to this disease. We were, however, not able to find an association of various clinical forms of the CD with a certain HLA haplotype in the followed group. CONCLUSION: The CD patients have in comparison with healthy population significantly different frequency of HLA class II haplotypes. Though the finding of these alleles is not sufficient for an explicit confirmation of this diagnosis, the proof of this risky haplotype/s may notably contribute to it, namely in case of potential or latent forms of this disease.

Increased levels of circulating ICAM-1, E-selectin, and IL-2 receptors in celiac disease.

Adhesive interactions between endothelium and circulating cells are crucial for the development of inflammatory reactions. We found significantly higher serum levels of soluble intracellular adhesion molecule-1 (sICAM-1, 492.5 +/- 22.1 ng/ml) in patients with active celiac disease (including IgA-deficient patients) than in patients on a gluten-free diet (335.7 +/- 20.0 ng/ml) (P < 0.001) and healthy controls (207.4 +/- 11.2 ng/ml) (P < 0.001). The concentration of soluble E-selectin in sera from celiac patients (37.2 +/- 3.4 ng/ml) was also higher (P < 0.001) than in sera from healthy controls (15.5 +/- 0.7 ng/ml) but, in contrast to sICAM-1, it remained high in the patients after treatment (30.2 +/- 2.7 ng/ml). Interestingly, the concentration of circulating soluble interleukin-2 receptors, molecules indicating lymphocyte activation, was only increased in sera from patients with active celiac disease (2943.0 +/- 214.1 pg/ml), and the level in sera from treated patients and healthy controls was comparable (1936 +/- 349 and 1416 +/- 111.7 pg/ml). The elevated serum level of soluble cell adhesion molecules could be used as a supplementary, noninvasive procedure for monitoring intestinal immune reactions.

HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children.

UNLABELLED: The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLA-DQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMA-positive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). CONCLUSION: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.

[Growth in children with the exudative enteropathy syndrome due to a congenital heart defect--cor triatriatum dextrum]. / Rust u dítete se syndromem exsudativní enteropatie na podklade vrozené srdecní vady--cor triatriatum dextrum.

Retarded growth in a child can be the sign of serious chronic disease. The authors present an account of a six-year-old boy where growth retardation persisted at least from the age of three. During this period his height dropped from the zone between the 25th and 50th percentile into the zone between the 3rd and 10th percentile. From the clinical point of view a large abdomen, loose stools and hypocalcaemia with tetany were striking, as they were moreover refractory to vitamin D2, calcitriol and calcium administration by the oral route. The authors revealed severe hypoproteinaemia, a 150 times increased value of alpha-1-antitrypsin in faeces, and exudative enteropathy syndrome was diagnosed. The cause was venous congestion due to a rare heart disease--cor triatriatum dextrum. The septum in the right atrium was resected. Immediately after surgery the consistency and frequency of stool decreased. Calcaemia and plasma protein levels reached normal levels within two months. A growth spurt of 11 cm/year followed. Fifteen months after operation the patient's height reached almost the 50th percentile.

[Endoscopic sclerotherapy of esophageal varices in children with prehepatic portal hypertension]. / Endoskopická skleroterapie jícnových varixu u detí s prehepatální portální hypertenzí.

BACKGROUND: Endoscopic sclerotization of oesophageal varices in adult patients with prehepatic portal hypertension has become the method of choice in haemorrhage from these varicosities. The objective of the present work was to prove the effectiveness of this treatment in children. METHODS AND RESULTS: Between November 1987 and May 1993 in the authors' departments endoscopic sclerotization was used to treat 20 children (age 2.5-17 years) with bleeding oesophageal varices (o.v.) associated with prehepatic portal hypertension (PPH), caused by thrombosis of the portal vein. Half the children were treated unsuccessfully before sclerotherapy by surgery, some repeatedly. Complete eradication of o.v. was achieved in 19 children (95%). In the course of sclerotherapy before completed obliteration of all varices 5 children (25%) had another spell of haemorrhage. In three instances this early relapse of haemorrhage was controlled by another sclerotization. In one patient continuing haemorrhage from an oesophageal varix was treated by establishment of a splenorenal anastomosis. In another patient the source of haemorrhage were gastric varices which were ligatured and after the operation the authors proceeded with sclerotherapy. A relapse of o.v. during the average 3-year follow up period was recorded in 7 children (35%), while a relapse of haemorrhage from these neovarices occurred only in one child (5%). CONCLUSIONS: Successful eradication of oesophageal varices by sclerotherapy in 95%, and 95% successful prevention of relapsing haemorrhage from neovarices for a period of three years after surgery justify a change of tactics of treatment. The method of first choice should be always sclerotization of bleeding varices.

[Histochemical and immunohistochemical study of jejunal mucosa cells in children with celiac sprue]. / Histochemické a imunohistochemické vysetrení bunek jejunální sliznice u detí s celiakální sprue.

In the jejunal mucosae of 45 children with coeliac sprue (24 cases in the florid stage and 21 cases in remission) and 19 children without signs of affection of the small intestine a quantitative investigation was made of cells in the lamina propria which were visualized selectively by histochemical and immunohistochemical methods-plasmocytes with IgA, plasmocytes with IgM, plasmocytes with IgG, cells containing IgE, mast cells, eosinophil and neutrophil leucocytes. The objective was to find which of the above cells will best reveal by a change of their number the pathological process in the lamina propria of children with coeliac sprue and which has the greatest informative value on the present state of the lamina propria. It was found that plasmocytes with IgG and cells containing IgE are good markers of the activity of coeliac sprue in the lamina propria. The best marker of the activity of coeliac sprue in the lamina propria are mast cells detected by the histochemical reaction for tryptase using Z-Ala-Ala-Lys-MNA. This reaction detects mast cells also in non-fixed bioptic material.