[Association of giant cell hepatitis and autoimmune hemolytic anemia in infancy]. / Óriássejtes hepatitis és autoimmun haemolyticus anaemia társulása kisdedkorban.

Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AIHA) is a rare disorder with unfavorable prognosis, affecting infants and young children. The mortality rate is high, complications of acute liver failure, sepsis, or liver transplantation can be responsible for fatal outcomes. An 18-month-old child who was diagnosed previously with autoimmune hemolytic anemia, developed acute hepatitis and acute liver failure concomitant to the relapse of the disease. GCH-AIHA is characterized by Coombs positive hemolytic anemia and progressive liver injury, histologically defined by widespread giant cell transformation. Liver biopsy was performed to establish the diagnosis, histological examination confirmed the presence of multinuclear, giant cell hepatocytes. Corticosteroid and azathioprine treatment were started. As a result of subsequent rituximab treatment and intravenous immunoglobulin therapy, acute liver failure and anemia gradually resolved. The exact background of the association of the two entities is still unknown, an autoimmune mechanism is suspected. Conventional immunosuppressive treatment with corticosteroid and azathioprine seems to be ineffective in most cases, therefore second- and third-line therapies are required. Since the introduction of the anti-CD20 rituximab therapy, the prognosis of GCH-AIHA has improved significantly. Orv Hetil. 2023; 164(36): 1432-1436.

Hungarian Linguistic, Cross-Cultural and Age Adaptation of Transition Specific Questionnaires in Patients with Inflammatory Bowel Disease.

Objective: In the TRANS-IBD clinical trial, the outcomes are measured with selected validated questionnaires. Cross-cultural and age adaptations of the Self-Efficacy Scale for adolescents and young adults (IBD-SES), the Transition Readiness Assessment Questionnaire (TRAQ), and the Self-Management and Transition Readiness Questionnaire (STARx) were performed. Methods: Linguistic and cultural adaptation was carried out with the usage of reliability coefficients (Cronbach's α coefficients, Spearman's rank correlation), and with confirmatory factor analysis (CFA; root Mean Square Error of Approximation [RMSEA], Comparative Fit Index [CFI], and Tucker-Lewis Index [TLI]). Results: 112 adolescents participated in the study (45.5% male, mean age 17 ± 1.98 years). CFA was acceptable in the IBD-SES and the TRAQ. Internal consistency was acceptable in IBD-SES and good in TRAQ (0.729; 0.865, respectively). Test-retest reliability was good in IBD-SES, but below the acceptable threshold in TRAQ (ρ = 0.819; ρ = 0.034). In STARx tools, RMSEA showed poor fit values, CFI and TLI were below acceptable fit values, and internal consistency was not satisfied (0.415; 0.693, respectively), while test-retest reliabilities were acceptable (ρ = 0.787; ρ = 0.788, respectively). Conclusions: Cross-cultural, age-specific adaptation was successfully completed with IBD-SES and TRAQ. Those are comparable to the original validated versions. The adaption of the STARx tools was not successful.

Disease Activity Is Associated with Obesity in Newly Diagnosed Pediatric Patients with Ulcerative Colitis.

Malnutrition and inflammatory bowel disease (IBD) are interrelated conditions. Our aim was to assess the prevalence of malnutrition, to compare anthropometric parameters in the evaluation of nutritional status in pediatric IBD, and to investigate the association between anthropometric parameters and disease activity indices (AI). Pediatric patients with newly diagnosed IBD recorded between 2010 and 2016 in the Hungarian Pediatric IBD Registry were included in this cross-sectional study. Body weight, body mass index (BMI), weight-for-height, and ideal body weight percent (IBW%) were analyzed. Pearson linear and non-linear correlations and polynomial regression analyses were performed to assess correlation between nutritional status and AI. p-values < 0.05 were considered significant. Anthropometric data of 1027 children with IBD (Crohn's disease (CD): 699; ulcerative colitis (UC): 328; mean age 13.7 years) were analyzed. IBW% identified more obese patients than BMI both in CD (7.02% vs. 2.28%) and UC (12.17% vs. 5.48%). Significant negative correlation was found among anthropometric parameters and AI in CD. In contrast, polynomial regression analysis revealed a U-shaped correlation curve between IBW% and AI in UC. Our findings show that obesity has a bimodal association with disease activity in pediatric UC. Furthermore, IBW% was more useful to identify obese pediatric patients with IBD.

Adherence to the Porto Criteria Based on the Hungarian Nationwide Pediatric Inflammatory Bowel Disease Registry (HUPIR).

Objectives: According to the Porto criteria, upper endoscopy and ileocolonoscopy with histology for patients with pediatric inflammatory bowel disease (pIBD) are recommended with small bowel imaging (SBI). We aimed to evaluate the adherence to the Porto criteria and biopsy sampling practice and to evaluate the diagnostic yield of magnetic resonance enterography (MRE) first time in a nationwide pIBD inception cohort. Methods: Newly diagnosed pIBD cases (ages 0-18 years) are registered in the prospective, nationwide Hungarian Paediatric IBD Registry (HUPIR). We analyzed the diagnostic workup of patients recorded between the 1st of January 2007 and the 31st of December 2016. Results: Data for diagnostic workup was available in 1,523 cases. Forty percent of the cases had complied with the Porto criteria. Adherence to the Porto criteria increased significantly from 20 to 57% (p < 0.0001) between 2007 and 2016. The most frequent reason for the incomplete diagnostic work-up was the lack of small bowel imaging (59%). In 2007, 8% of cases had a biopsy from all segments, and this rate reached 51% by 2016 (p < 0.0001). We analyzed the diagnostic yield of MRE in 113 patients (10.1%), who did not have any characteristic lesion for Crohn's disease. The MRE was positive for the small bowel in 44 cases (39%). Conclusions: Adherence to the Porto criteria increased significantly during the 10-year period. This is the first study that reports multiple biopsy sampling as the less accepted recommendation. The diagnostic yield of MRE in patients without characteristic lesion for Crohn's disease is 39%.

Effect of joint transition visits on quality of life in adolescents with inflammatory bowel diseases: a protocol for a prospective, randomised, multicentre, controlled trial (TRANS-IBD).

INTRODUCTION: Inflammatory bowel diseases (IBD) are among the most common chronic illnesses diagnosed in childhood. Transition from paediatric to adult care is a crucial phase. The implementation of joint visits during the transition period in IBD is widely recommended, however, strong evidence supporting their benefit is still missing. In this trial, we aim to prove the superiority of joint visits compared with usual care in improving transition outcomes of adolescents with IBD. METHODS AND ANALYSIS: This is a randomised controlled two-arm multicentre trial. A minimum of 160 adolescents with IBD aged between 16.75 and 17 years will be recruited from Hungarian tertiary IBD centres. After randomisation, eligible subjects in the intervention arm attend a total of four joint visits with adult and paediatric gastroenterologist between the ages of 17 and 18. In the control arm, adolescents meet only the paediatric gastroenterologist, but there is a balanced consultation between the two gastroenterologist regarding the patient's treatment plan. Patients in both groups receive the same training and education, the only determinative difference between the two arms is the presence of the adult gastroenterologist at the joint visits. Data will be collected at inclusion, at transfer and 12 months post-transfer. Primary outcome is the change in health-related quality of life measured with the IMPACT-III questionnaire at 1 year after transfer. Secondary outcomes include the number of patients not lost to follow-up, healthcare utilisation, disease activity, medication adherence, self-efficacy, transition readiness and patient's satisfaction. To compare the results of the two patient groups, two-sample T-test and Mann-Whitney test will be applied. ETHICS AND DISSEMINATION: The Scientific and Research Ethics Committee of the Hungarian Medical Research Council approved this study (50457-2/2019/EKU). Findings will be disseminated at conferences and in medical journals. TRIAL REGISTRATION NUMBER: NCT04290156.

A Cross-Sectional Survey on the Transitional Care of Adolescents with Inflammatory Bowel Disease in Hungary.

PURPOSE: Since little is known about transitional care practices of adolescents with inflammatory bowel diseases (IBD) in Central-Eastern Europe, we aimed to investigate the currently applied transition practices in Hungary. DESIGN AND METHODS: A nationwide, multicentre survey was conducted with the invitation of 41 pediatric and adult IBD centres in February 2019.We developed a 34-item questionnaire, which included single- and multiple-choice questions related to the current clinical practice of IBD transition. RESULTS: The overall response rate was 31.7% (13/41); answers came predominantly from tertiary centres. Only 15.4% of the respondent centres followed international IBD guidelines. The majority of the IBD centres provided transition support; however, responses revealed a marked heterogeneity of these services. Joint visits were held only in 54% of the clinics. Gastroenterologists and next of kin are not provided education regarding transition across most centres (85 and 92%). Although adolescents received age-specific education, transition readiness was not measured. More IBD nurses and dietitians were employed in adult centres than in pediatric ones. CONCLUSIONS: The current survey revealed critical gaps in the Hungarian IBD transition practices. As the beneficial effects of structured IBD transition programmes are recognized in Hungary, there is a growing need for the introduction of new, more effective transition practices. PRACTICE IMPLICATIONS: Our results can serve as a basis for planning more effective transition strategies.

Planned Transition of Adolescent Patients with Inflammatory Bowel Disease Results in Higher Remission Rates.

PURPOSE: To evaluate the effect of our current transition process on clinical outcomes in adolescent patients with inflammatory bowel diseases (IBD). DESIGN AND METHODS: Two groups of patients with IBD diagnosed in pediatric care were compared retrospectively: Group A patients did not attend the transition process, while Group B patients entered the planned transition service. Outcomes at 1-year after transfer to adult care were evaluated. RESULTS: Forty-five patients with IBD diagnosed under the age of 18 years were identified of whom 35 had Crohn's disease and 10 had ulcerative colitis. Twenty-four patients were in Group A (without transition), and 21 patients in Group B (with at least one planned transition visit). Mean age at diagnosis was 15.1 ±â€¯2.2 and 13.7 ±â€¯3.0 years (p = 0.086), respectively. There were no significant differences in disease duration before transfer, Montreal classification at diagnosis, body mass index, anti-TNF therapy usage, and disease status at transfer between the two groups. A significantly higher number of Group B patients were in remission at 12 months after transfer when compared to patients in Group A (11 vs. 18, respectively, p = 0.037). There was a significant difference between groups regarding the number of scheduled visits within the examined period (9 vs. 16, p = 0.011, respectively). CONCLUSIONS: Planned transition visits resulted in higher disease remission rate at 1-year follow-up after transfer from pediatric to adult health care system in adolescent patients with IBD. PRACTICE IMPLICATION: Well-established transition programs in IBD are needed.

[Frequency of serious adverse events of thiopurine treatment in normal thiopurine S-methyltransferase genotype children with inflammatory bowel disease]. / A tiopurinkezelés súlyos mellékhatásainak gyakorisága normális tiopurin-S-metiltranszferáz-genotípusú gyulladásos bélbetegségben szenvedo gyermekekben.

INTRODUCTION: Genetic polymorphism of thiopurine S-methyltransferase, the key enzyme in metabolism of thiopurines (azathioprine and 6-mercaptopurine) used in the treatment of inflammatory bowel disease, results in different enzyme activities. Decreased enzyme activity causes myelosuppression whereas abnormally high activity results in hepatotoxicity at standard thiopurine doses. Four allele variants (TMPT*2, TMPT*3A, TPMT*3B and TPMT*3C) account for decreased activity in more than 95% of cases. AIM: To evaluate the frequency of severe side effects, such as myelosuppression and hepatotoxicity, at standard or decreased azathioprine doses in children with inflammatory bowel disease who do not exhibit any of the four most common variant alleles. METHOD: Retrospective analysis of children with inflammatory bowel disease treated with azathioprine at a single tertiary referral center. RESULTS: 51 patients were identified (44: Crohn's disease, 7: ulcerative colitis; male ratio: 28/51; mean age at diagnosis: 12.4 years). Two patients discontinued azathioprine arbitrarily whereas in one patient it was stopped due to serious pancreatitis and in another one because of severe flu-like symptoms. None of the remaining 47 patients exhibited hepatotoxicity suggesting abnormally high thiopurine S-methyltransferase activity. Four patients (8.5%) had profound myelosuppression on less than 1 mg/kg/day azathioprine requiring discontinuation of the drug, and all of them showed complete bone marrow recovery subsequently. No myelosuppression occurred in the remaining 43 patients on 2.17 ± 0.31 mg/kg/day (mean ± SD) azathioprine treatment. CONCLUSIONS: Regular blood tests are necessary on thiopurine therapy despite normal thiopurine S-methyltransferase genotype because of the risk of myelosuppression. The four most common variant alleles were identified in routine genotyping only, therefore most likely rare variant allele(s) or polymorphism of other enzymes involved in thiopurine metabolism account for the aforementioned four cases with profound bone marrow suppression. Thiopurine metabolite monitoring is the key for individualized treatment when optimal dosing can be achieved with the least side effects. Orv Hetil. 2019; 160(5): 179-185.

Characteristics of biological therapy in pediatric patients with Crohn's disease.

INTRODUCTION: At present, there is a significant amount of data related to biologics used in pediatric patients with Crohn's disease. This review characterizes the different biological drugs administered in this population. AREAS COVERED: Biological therapy of CD, focusing on children, is summarized in this review. After mechanism of action and pharmacokinetics are described, mucosal healing on anti-TNF therapy, aspects of early therapy, long-term outcome and combination therapy are discussed. Moreover, loss of response and treatment optimization, as well as drug withdrawal are summarized. Subsequently, perianal disease and surgical aspects are discussed followed by safety issues. In addition, new drugs (vedolizumab, ustekinumab), cost-effectiveness and administration of biosimilars were also included. EXPERT COMMENTARY: There are significant data to characterize biological drugs administered in pediatric patients with Crohn's disease. However, head-to-head comparative studies using different biologics are missing.

Elevated urinary orosomucoid excretion as a novel biomarker in Crohn's disease.

BACKGROUND: Laboratory markers are essential tools in the follow-up of patients with Crohn's disease (CD). Our aim was to investigate urinary concentrations of orosomucoid in relation to the inflammatory activity of CD and to compare it with clinical indices and conventional laboratory parameters. MATERIALS AND METHODS: Blood and urine samples of 86 patients (55 adults and 31 children) with CD and 68 healthy individuals (38 adults and 30 children) as controls were analysed. Patients were categorized according to their clinical scores (Harvey-Bradshaw Index [HBI] or Pediatric Crohn's Disease Activity Index [PCDAI]). Urinary orosomucoid (u-ORM) was determined by automated immune turbidimetric assay, and values were referred to urinary creatinine (u-ORM/u-CREAT, mg/mmol). RESULTS: U-ORM/u-CREAT values were seven times higher in children with active CD (0.50 vs 0.07 mg/mmol, P < 0.001) and two times higher in adults (0.32 vs 0.14 mg/mmol, P = 0.01) compared with patients with inactive disease. U-ORM/u-CREAT showed good correlation with conventional inflammatory markers (hs-CRP, serum ORM; P < 0.01) and activity indices (HBI, P = 0.018; PCDAI, P < 0.001). U-ORM/u-CREAT had similar discriminative performance to hs-CRP and serum ORM in the differentiation of active from inactive paediatric CD patients. CONCLUSIONS: Our findings suggest that u-ORM/u-CREAT might serve as a valuable additional marker in the follow-up of CD patients, especially in children for whom the non-invasive sampling is a further advantage.

Baseline Characteristics and Disease Phenotype in Inflammatory Bowel Disease.

OBJECTIVES: Predicting short-term relapses and long-term prognosis is of utmost importance in paediatric inflammatory bowel disease (IBD). Our aim was to investigate the short-term disease outcome and medication during the first year in a paediatric incident cohort from Hungary. In addition, association laboratory markers and disease activity indices with short-term disease outcome and medication were analysed. METHODS: From January 1, 2008 to December 31, 2010, demographic data and clinical characteristics of newly diagnosed paediatric patients with IBD < 18 years of age were prospectively recorded. RESULTS: A total of 420 patients were identified (Crohn disease [CD] 266 and ulcerative colitis [UC] 124). Initially, 48% (124/256) of the patients with CD had moderate-to-severe disease (Pediatric Crohn's Disease Activity Index [PCDAI] > 31), and this rate decreased to 2.1% at 1-year follow-up. Proportion of patients with UC with moderate-to-severe disease (Pediatric Ulcerative Colitis Activity Index > 35) at diagnosis declined from 57.5% (69/120) to 6.8% at 1-year follow-up. Terminal ileal involvement correlated with higher initial C-reactive protein (CRP) (P = 0.021) and initial PCDAI (P = 0.026). In UC, elevated CRP (P = 0.002) was associated with disease extension. CRP and PCDAI at diagnosis were associated with the need for immunomodulators at 1 year in children with CD. Initial CRP was also associated with the need for immunomodulators in patients with UC at 1-year follow-up. CONCLUSIONS: At diagnosis, half of the patients with IBD had moderate-to-severe disease, and this rate decreased to <10% after 1 year. Initial CRP and PCDAI were related to the need for aggressive therapy in CD.

Low n-3 long-chain polyunsaturated fatty acids in newly diagnosed celiac disease in children with preexisting type 1 diabetes mellitus.

OBJECTIVE: Fat malabsorption can occur in celiac disease (CD) owing to villus atrophy and inflammation of small intestinal mucosa. Abnormal fatty acid (FA) status of intestinal mucosa in children with CD was reported earlier. Previously we found significantly reduced availability of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) in children and young adults with type 1 diabetes mellitus (DM). The aim of this study was to investigate FAs in plasma lipid classes in children with newly diagnosed CD with or without preexisting DM. METHODS: FA composition of plasma samples of children with untreated CD only (n = 20) and with preexisting DM (CDDM, n = 8) were compared with those of healthy controls (n = 21). Detailed analysis of phospholipid, triacylglycerol, and sterol ester FAs was performed by high-resolution capillary gas-liquid chromatography. RESULTS: Significantly decreased docosapentaenoic (C22:5n-3), docosahexaenoic (C22:6n-3), n-3 polyunsaturated fatty acids (n-3 PUFA), and n-3 LCPUFA values were found in CDDM group compared with controls and patients with CD. When compared with healthy controls, no significant difference was found in plasma FAs of children with newly diagnosed CD only. CONCLUSIONS: Children with CDDM showed marked signs of reduced availability of n-3 PUFA and n-3 LCPUFA in circulating lipids. Although different tissues express membrane FAs differently, our present study suggests that CD on its own does not necessarily lead to detectable disturbances of essential FA metabolism in plasma and supports the concept that DM has significant impact on plasma FA composition in children.

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.

Diagnostic yield of upper endoscopy in paediatric patients with Crohn's disease and ulcerative colitis. Subanalysis of the HUPIR registry.

BACKGROUND, AIMS: According to Porto Criteria upper gastrointestinal (UGI) endoscopy is recommended in patients with suspected inflammatory bowel disease (IBD). Nevertheless, previous studies revealed frequent involvement of UGI tract even in patients with ulcerative colitis (UC). The aim of the present study was to determine the diagnostic role of esophagogastroduodenoscopy (EGD) and assess the prevalence and different aspects of UGI involvement in children registered in the Hungarian Pediatric IBD Registry (HUPIR) from 1st of January 2007 to 31th of December 2009. METHODS: Twenty seven institutes provided prospective follow-up data about newly diagnosed IBD patients to HUPIR. The registry was based on detailed questionnaire (76 parameters) involving anamnestic data, laboratory findings, activity indexes, diagnostic procedures, endoscopic examinations (EGD and ileocolonoscopy), and histological data. Localization and phenotype of disease were based on the Montreal classification criteria. RESULTS: During the 3-year period 420 children were diagnosed with IBD, 265 (63%) of them had Crohn's disease (CD), 130 (31%) UC, and 25 (6%) IBD-unclassified (IBD-U). The mean age at diagnosis was 13.2 years (range: 1.2-18 years). EGD was performed in 237 patients (56%), in most cases in patients suffering from CD. Macroscopic lesions on EGD were noted in 64% of patients with CD and 40% of children with UC. Characteristic lesions for CD (ulcer, erosion, aphthous lesion, and granuloma) were noted in 31% of CD patients, however, EGD helped to establish the final diagnosis in 9% of CD patients (diagnostic yield, 9%). CONCLUSIONS: There was a high frequency of UGI involvement in children with CD and UC. One third of CD patients showed significant lesions at upper endoscopy and one patient out of ten had real diagnostic help from EGD.

Gastrointestinal malformations, associated congenital abnormalities, and intrauterine growth.

BACKGROUND: In contrast with other malformations, congenital anomalies of the gastrointestinal tract have been scarcely investigated. METHODS: The prevalence of gastrointestinal malformations with special reference to associated disorders and intrauterine growth was retrospectively analyzed in the newborn infants admitted to the Neonatal Intensive Care Unit of the Department of Pediatrics, University of Pécs, Hungary, in the 14-year period between 1987 and 2000. RESULTS: Of 4,241 neonates with gastrointestinal malformations, 241 (5.68%) had a total of 304 malformations (excluding Hirschsprung disease). In 133 patients, the gastrointestinal anomalies were observed as one of multiple malformations; a specific syndrome or association was diagnosed in 36 cases. Skeletal disorders were the most frequently associated anomalies. Intrauterine growth retardation was found in a large number of patients with both isolated and multiple gastrointestinal malformations (38.9% and 30.8%, respectively). CONCLUSIONS: Gastrointestinal malformations often are complicated by skeletal anomalies and intrauterine growth retardation. The association among these disorders requires further investigation. However, from a practical point of view, this association should be considered in treating affected patients.