Antal Dezsőfi

Liver biopsy in children: position paper of the ESPGHAN Hepatology Committee.

Liver biopsy (LB) is still the criterion standard procedure for obtaining liver tissue for histopathological examination and a valuable tool in the diagnosis, prognosis, and management of many parenchymal liver diseases. The aim of this position paper is to summarise the present practice of paediatric LB and make recommendations about its performance. Although histological evaluation of the liver is important in assessing prognosis and exploring treatment, noninvasive techniques (ie, imaging, laboratory markers) may replace use of liver histology. The indications for LB are changing as present knowledge of aetiologies, pathomechanism, and therapeutic options in paediatric liver disease is evolving. Adult and paediatric literature was reviewed to assess the existing clinical practice of LB with focus on the technique, indications, risk of complications, and contraindications in paediatrics. This position paper presents types of LB, indications, complications, contraindications, and an essential checklist for paediatric LB.

Incidence, Paris Classification, and Follow-up in a Nationwide Incident Cohort of Pediatric Patients With Inflammatory Bowel Disease

Objectives: The aim of the study was to evaluate the incidence, baseline disease characteristics, and disease location based on the Paris classification in pediatric inflammatory bowel disease (IBD) in the Hungarian nationwide inception cohort. In addition, 1-year follow-up with therapy was analyzed. Methods: From January 1, 2007 to December 31, 2009, newly diagnosed pediatric patients with IBD were prospectively registered. Twenty-seven pediatric gastroenterology centers participated in the data collection ensuring the data from the whole country. Newly diagnosed patients with IBD younger than 18 years were reported. Disease location was classified according to the Paris classification. Results: A total of 420 patients were identified. The incidence rate of pediatric IBD was 7.48/105 (95% confidence interval [CI] 6.34/105–8.83/105). The incidence for Crohn disease (CD) was 4.72/105 (95% CI 3.82–5.79), for ulcerative colitis (UC) 2.32/105 (95% CI 1.71–3.09), and for IBD-unclassified 0.45/105 (95% CI 0.22–0.84). Most common location in CD was L3 (58.7%); typical upper gastrointestinal abnormalities (ulcer, erosion and aphthous lesion) were observed in 29.9%. Extensive colitis in patients with UC (E4, proximal to hepatic flexure) was the most common disease phenotype (57%), whereas only 5% of children had proctitis. A total of 18.6% of patients had ever severe disease (S1). Frequency of azathioprine administration at diagnosis was 29.5% in patients with CD, and this rate increased to 54.6% (130/238) at 1-year follow-up. In UC, only 3.3% received azathioprine initially, and this rate elevated to 22.5% (25/111). Use of corticosteroid decreased from 50% to 15.3% in patients with UC. Rate of bowel resection in patients with CD during the first year of follow-up was 5%. Conclusions: The incidence of pediatric IBD in Hungary was among the higher range reported. This is the first large, nationwide incident cohort analyzed according to the Paris classification, which is a useful tool to determine the characteristic pediatric CD phenotype.

Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease

Duodenal biopsy is an important tool to diagnose coeliac disease (CD); however, the most reliable location of biopsy site is still questionable. Claudins (CLDNs), members of a large family of adherent junction proteins, show characteristic expression pattern in inflammatory disorders; nevertheless, CLDN expression in CD is unknown. This is a comparative study to examine the CLDN 2, 3 and 4 expressions in proximal and distal part of duodenum in children with CD and in controls. Thirty-three children with newly diagnosed CD were enrolled. Fourteen healthy children served as controls. Biopsies from proximal and distal part of duodenum were taken for routine histological analysis. Immunohistochemistry were used to detect CD3+ intraepithelial lymphocytes and CLDN 2, 3 and 4 protein expressions. Macroscopic picture, routine histology and Marsh grade depicted no differences between biopsies taken from proximal or distal part of duodenum. However, CLDN 2 expression was significantly increased in severe form of coeliac disease in bulb and in distal duodenum, and in distal part of non-severe coeliac patients, in comparison to controls. Similar association was found concerning CLDN 3 expression. Expression of CLDN 4 was similar in all groups studied. Both proximal and distal mucosal duodenal biopsies are suitable for diagnosing villous atrophy in patients with CD. Increased expressions of CLDN 2 and 3 suggest structural changes of tight junction in coeliac disease which may be, at least in part, responsible for increased permeability and proliferation observed in coeliac disease.

Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease

A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD (n = 10), with CD on gluten-free diet (GFD) (n = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.

Liver biopsy in children 2014: Who, whom, what, when, where, why?

Liver biopsy is the standard procedure for obtaining hepatic tissue for histopathological examination. The three major techniques are percutaneous, transvenous, and laparoscopic/open biopsy, with either cutting or suction needles. The indications for liver biopsy are shifting as knowledge of etiologies, non-invasive biomarker alternatives, and treatment options in paediatric liver disease expand. This mini-review presents specific indications, alternative approaches, methods, complications, and contraindications for paediatric liver biopsy.

Autoregressive cross-lagged models of IMPACT-III and Pediatric Crohn's Disease Activity indexes during one year infliximab therapy in pediatric patients with Crohn's disease

BACKGROUND Quality of life (QoL) is an important outcome measure in the evaluation of therapies for inflammatory bowel disease. The primary aim of this study was to determine the effect of one year infliximab treatment on QoL and clinical parameters in pediatric patients with Crohns diseases (CD). METHODS Our prospective study involved 51 children with conventional therapy resistant, severe CD (mean age: 15.25years, range: 11-18years). Infliximab was given according to the protocol (5mg/kg, at weeks 0, 2, 6 and every 8weeks). During the infliximab courses QoL of patients was evaluated by IMPACT-III questionnaire at weeks 0, 6, 30 and 53. At the same time, the Pediatric Crohns Disease Activity Index (PCDAI) score was calculated. Moreover, serum C-reactive protein (CRP), serum platelets and serum albumin were followed up. Auto-regressive, cross-lagged models were used to assess relation between QoL and the clinical parameters. RESULTS The initial IMPACT-III scores [median, percentile 25-75 (pc 25-75) at week 0: 115, 102.5-130.25] increased significantly (p<0.001) following infliximab therapy at week 54 (median: 141.5, 124.5-153.75). Clinical and laboratory parameters also improved significantly (p<0.001). Auto-regressive regression coefficients (β value) were significant between each variable over time. The strongest cross-lagged relations were observed between IMPACT-III and serum albumin, IMPACT-III and platelets. Reliability test of IMPACT-III revealed an excellent level of internal consistency (Cronbachs alpha=0.931). CONCLUSION Infliximab treatment has beneficial clinical effect which is confirmed by decrease of PCDAI and increase of IMPACT-III. Autoregressive regression analysis showed regression relation between IMPACT-III and PCDAI and laboratory parameters.

Polymorphisms of the TNF-α gene and risk of celiac disease in T1DM children

Background:  Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the −308A variant of the tumor necrosis factor‐α (TNF‐α) gene is associated either with T1DM or with CD. The aim of our study was to determine whether −308A and −238A allelic variants of the TNF‐α gene might have any impact on the risk of CD in T1DM children.

Seasonal variability of vitamin D and bone metabolism in infliximab-treated paediatric Crohn's disease.

BACKGROUND Paediatric Crohns disease patients suffer from several complications, including low bone mineral density and inadequate serum levels of 25-hydroxy vitamin D. AIMS The aim of this prospective study was to address the effect of infliximab therapy on bone metabolism, bone mineral density and vitamin D homeostasis. The seasonal variability of serum vitamin D levels in relation to infliximab treatment was also analysed. METHODS Serum osteocalcin and beta-crosslaps (markers of bone metabolism), seasonal variability of vitamin D, and bone mineral density were assessed and followed throughout the yearlong treatment regimen of infliximab in 50 consecutive paediatric patients with moderate to severe Crohns disease. RESULTS Bone forming osteocalcin levels were significantly (p<0.001) increased during infliximab therapy. In contrast, no significant changes in beta-crosslaps and vitamin D levels were observed. Vitamin D levels were significantly different when the summer and winter periods were compared at week 0 (p=0.039); however, this difference was not detected after one year of infliximab therapy. Despite the beneficial clinical effect of infliximab, there was no significant change in bone mineral density Z-scores after one year of treatment. CONCLUSION Infliximab may beneficially affect bone homeostasis. Moreover, seasonal variability in vitamin D levels observed prior to initiation of infliximab treatment was diminished after one year of treatment.

Hepatic neoplasms in children: A focus on differential diagnosis

Paediatric hepatic neoplasias are rare, accounting for 1-4% of all solid childhood tumors. Liver tumors in children can be classified into benign or malignant; some of the benign lesions can have the potential of malignant transformation. Two-thirds of liver tumors in children are malignant. Hepatoblastoma accounts for two-thirds of malignant liver tumors in children. Other liver malignancies in children include sarcomas, germ cell and rhabdoid tumours, and hepatocellular carcinoma. Benign tumors of the liver in children include vascular tumours, hamartomas, adenomas, and focal nodular hyperplasia. The histology and anatomy of a paediatric liver tumour guides the treatment and prognosis. Although benign and malignant liver masses share some clinical manifestations, treatment and prognosis differ.

Analysis of infliximab treated pediatric patients with Crohn disease in Hungary

Infliximab, the chimeric antibody to tumor necrosis factor-alpha, is indicated for medically refractory pediatric Crohn disease. Aim of our study was to examine the efficacy and side effects of infliximab therapy in Hungarian pediatric patients with Crohn disease since the authorisation of medicine for children to 31.12.2008. 23 children with refractory Crohn disease received infliximab during this period. Induction therapy with 5 mg/kg infliximab at weeks 0, 2, and 6 was introduced. 18 patients (81.8%) achieved clinical response, and 13 patients (59.1%) were in remission at the 6th week of the observation period. The evaluation was based on data of 22 children. Fistula closure rate was 70% at the at the 6th week. Two patients had acute infusion reaction, one had severe anaphilactic reaction after infliximab infusion. Chronic side effects were also observed in three cases. In our study infliximab induction therapy was effective in most pediatric patients with therapy refractory Crohn disease.