Real-life efficacy of vedolizumab on endoscopic healing in inflammatory bowel disease - A nationwide Hungarian cohort study.

Background: GEMINI trials demonstrated the therapeutic efficacy of vedolizumab (VDZ) in Crohn's disease (CD) and ulcerative colitis (UC).Research design and methods: Aim of this study was to determine the real-life effectiveness of VDZ on endoscopic healing in the Hungarian nationwide cohort of inflammatory bowel disease (IBD) patients based on the changes on clinical and endoscopic scores. Every adult IBD patient in the country (121 UC and 83 CD) who completed the short-term VDZ therapy was enrolled, of which 72 UC and 52 CD patients could complete the long-term therapy.Results: The rates of endoscopic healing were substantially higher in UC compared with CD patients during the short- and long-term therapy (52.9% vs. 21.7%, p < 0.0001, and 51.4% vs. 21.2%, p = 0.015, respectively). In CD, the rate of endoscopic healing was lower at week 14 compared with week 22 (14.5% vs. 37.0%, p = 0.026). Prior anti-TNF-α therapy (88.73%) was not associated with a significant decrease in therapeutic response. The average disease duration was significantly lower in CD patients achieving endoscopic healing at week 52 (11.75 vs. 5.27 years, p = 0.007).Conclusions: VDZ therapy is an effective therapeutic option in anti-TNF-α refractory IBD. However, the endoscopic healing rate was substantially lower and showed a significant delay in CD compared with UC.

[Long-term adalimumab therapy in ulcerative colitis in clinical practice: result of the Hungarian multicenter prospective study]. / Az adalimumab hatékonysága és biztonságossága hagyományos kezelésre refrakter colitis ulcerosában.

INTRODUCTION: Adalimumab was approved for the treatment of ulcerative colitis refractory to conventional therapy several years later than infliximab in Europe. Due to the relatively low remission rate observed in Ultra trials, data on the efficacy of adalimumab in ulcerative colitis are really helpful in the daily practice. AIM: The aim of this study was to prospectively collect data on induction and maintenance adalimumab therapy in patients with ulcerative colitis treated in Hungarian centres. METHOD: This prospective study collected data of all patients with ulcerative colitis treated with adalimumab in 10 Hungarian centres. The primary endpoints of the study were rates of remission, response and primary failure at week 12, and the rate of continuous clinical response, remission and loss of response at weeks 30, and 52. Secondary endpoints were endoscopic outcome at week 52 and comparison of the efficacy of adalimumab between treatment naive and infliximab-experienced patients. RESULTS: 73 patients with active ulcerative colitis were enrolled in the study. 75.3% of the patients exhibited clinical response after the induction at week 12. The probability of maintaining adalimumab treatment was 48.6% at week 52 with a continuous clinical response in 92% of these patients. Mucosal healing was achieved in 48.1% of the patients at week 52. Dose intensification was performed in 17.6% of the patients. Minor side effects developed in 4% of the patients and 5.4% of the patients underwent colectomy during the 1-year treatment period. CONCLUSIONS: These results coming from the real clinical setting demonstrate a favourable efficacy of adalimumab induction and maintenance therapy in patients with ulcerative colitis.

Efficacy and Safety of Adalimumab in Ulcerative Colitis Refractory to Conventional Therapy in Routine Clinical Practice.

BACKGROUND AND AIM: Adalimumab [ADA] was approved for the treatment of ulcerative colitis [UC] refractory to conventional therapy in 2012 in Europe. Due to the observed discrepancies between clinical trials and practice, data on the outcome of ADA therapy are really needed from the real life. The aim of this study was to estimate the short- and long-term efficacy and safety of ADA in UC patients from each Hungarian biological centre. PATIENTS AND METHODS: This prospective study consisted of UC patients treated with ADA in 10 Hungarian inflammatory bowel disease centres. The primary endpoints of the study were rates of continuous clinical response, remission, non-response and loss of response at Weeks 12, 30, and 52.The secondary endpoints included mucosal healing at Week 52 and the comparison of the efficacy of ADA between biological naive and infliximab [IFX]-treated groups. Colonoscopy was performed before starting the therapy and at Week 52. RESULTS: In all, 73 active UC patients were enrolled in the study: 67.1% of the patients received previous IFX therapy; 75.3% of the patients showed short-term clinical response at Week 12. The probability of maintaining ADA was 48.6% at Week 52 with a continuous clinical response in 92% of these remaining patients. Mucosal healing was achieved in 48.1% of the patients at Week 52. Escalation of ADA was performed in 17.6%, and minor side effects developed in 4% of the patients; 5.4% of the patients underwent colectomy during the 1-year treatment period. CONCLUSION: UC is a progressive disease that may need early aggressive therapy to prevent structural and functional complications. The results of our study demonstrated the favourable efficacy of short- and long-term ADA treatment for patients with UC.

Efficacy and Safety of the Biosimilar Infliximab CT-P13 Treatment in Inflammatory Bowel Diseases: A Prospective, Multicentre, Nationwide Cohort.

BACKGROUND AND AIMS: Biosimilar infliximab CT-P13 is approved for all indications of the originator product in Europe. Prospective data on its efficacy, safety, and immunogenicity in inflammatory bowel diseases are lacking. METHODS: A prospective, nationwide, multicentre, observational cohort was designed to examine the efficacy, safety, and immunogenicity of CT-P13 infliximab biosimilar in the induction treatment of Crohn's disease [CD] and ulcerative colitis [UC]. Demographic data were collected and a harmonised monitoring strategy was applied. Early clinical remission, response, and early biochemical response were evaluated at Week 14, steroid-free clinical remission was evaluated at Week 30. Therapeutic drug level was monitored using a conventional enzyme-linked immunosorbent assay. RESULTS: In all, 210 consecutive inflammatory bowel disease [126 CD and 84 UC] patients were included in the present cohort. At Week 14, 81.4% of CD and 77.6% of UC patients showed clinical response and 53.6% of CD and 58.6% of UC patients were in clinical remission. Clinical remission rates at Week 14 were significantly higher in CD and UC patients who were infliximab naïve, compared with those with previous exposure to the originator compound [p < 0.05]. Until Week 30, adverse events were experienced in 17.1% of all patients. Infusion reactions and infectious adverse events occurred in 6.6% and 5.7% of all patients, respectively. CONCLUSIONS: This prospective multicentre cohort shows that CT-P13 is safe and effective in the induction of clinical remission and response in both CD and UC. Patients with previous infliximab exposure exhibited decreased response rates and were more likely to develop allergic reactions.

Is rectal indomethacin effective in preventing of post-endoscopic retrograde cholangiopancreatography pancreatitis?

AIM: To investigate the effectiveness of rectally administered indomethacin in the prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasaemia in a multicentre study. METHODS: A prospective, randomised, placebo-controlled multicentre study in five endoscopic units was conducted on 686 patients randomised to receive a suppository containing 100 mg indomethacin, or an inert placebo, 10-15 min before ERCP. Post-ERCP pancreatitis and hyperamylasaemia were evaluated 24 h following the procedure on the basis of clinical signs and laboratory parameters, and computed tomography/magnetic resonance imaging findings if required. RESULTS: Twenty-one patients were excluded because of incompleteness of their data or because of protocol violation. The results of 665 investigations were evaluated: 347 in the indomethacin group and 318 in the placebo group. The distributions of the risk factors in the two groups did not differ significantly. Pancreatitis developed in 42 patients (6.3%): it was mild in 34 (5.1%) and severe in eight (1.2%) cases. Hyperamylaesemia occurred in 160 patients (24.1%). There was no significant difference between the indomethacin and placebo groups in the incidence of either post-ERCP pancreatitis (5.8% vs 6.9%) or hyperamylasaemia (23.3% vs 24.8%). Similarly, subgroup analysis did not reveal any significant differences between the two groups. CONCLUSION: 100 mg rectal indomethacin administered before ERCP did not prove effective in preventing post-ERCP pancreatitis.

[Role of pulse oximetric monitoring during gastrointestinal endoscopy. Prospective multicenter study of the Gastroenterology Working Group of the Veszprém Regional Committee of the Hungarian Academy of Sciences (VEAB)]. / Az endoszkópos vizsgálatok pulzoximetriás monitorozásának jelentosége. Az MTA VEAB Gasztroenterológiai Munkabizottságának prospektív multicentrikus vizsgálata.

INTRODUCTION: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units. AIMS: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy. METHOD: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation. RESULTS: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors. CONCLUSION: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia.

[Effects of rectal indomethacin in the prevention of post-ERCP acute pancreatitis]. / Az indometacin szerepe az endoszkópos retrográd cholangiopancreatographiát követo akut pancreatitis prevenciójában.

UNLABELLED: Recently non-steroidal anti-inflammatory drugs have seemed to reduce the frequency of post-ERCP pancreatitis in some prospective controlled trials, but the results have to be confirmed by further studies. AIM: To evaluate the efficacy of rectally administered indomethacin for the reduction of incidence of post-ERCP pancreatitis. METHOD: A prospective randomized placebo-controlled study was conducted in 228 patients who underwent ERCP. Patients were randomized to receive a suppository containing 100 mg indomethacin or an inert placebo 10 mins before ERCP. Patients were evaluated clinically and biochemically by using serum amylase levels measured 24 h after the procedure. RESULTS: Pancreatitis and hyperamylasemia occurred more frequently in the placebo group, but the difference was not significant. In respect to the rate of pancreatitis, this tendency could particularly be observed in females, in patients older than 60 years and in patients with BMI lower than 25; however, it completely failed in cases with pancreatic duct filling or in those with pancreatic EST. CONCLUSIONS: Rectal indomethacin given before ERCP did not prove to be statistically effective in the reduction of the incidence of post-procedure pancreatitis. Further, controlled multicenter studies are required to assess safely the potential efficacy of indomethacin in the prevention of pancreatitis following ERCP.

Capsaicin-sensitive afferentation represents an indifferent defensive pathway from eradication in patients with H. pylori gastritis.

AIM: To study the role of capsaicin-sensitive afferent nerves in Helicobacter pylori (H. pylori) positive chronic gastritis before and after eradication. METHODS: Gastric biopsy samples were obtained from corpus and antrum mucosa of 20 healthy human subjects and 18 patients with H. pylori positive chronic gastritis (n = 18) before and after eradication. Traditional gastric mucosal histology (and Warthin-Starry silver impregnation) and special histochemical examinations were carried out. Immunohistochemistry for capsaicin receptor (TRVP1), calcitonin gene-related peptide (CGRP) and substance P (SP) were carried out by the labeled polymer immunohistological method (Lab Vision Co., USA) using polyclonal rabbit and rat monoclonal antibodies (Abcam Ltd., UK). RESULTS: Eradication treatment was successful in 16 patients (89%). Seven patients (7/18, 39%) remained with moderate complaints, meanwhile 11 patients (11/28, 61%) had no complaints. At histological evaluation, normal gastric mucosa was detected in 4 patients after eradication treatment (4/18, 22%), and moderate chronic gastritis could be seen in 14 (14/18, 78%) patients. Positive immuno-staining for capsaicin receptor was seen in 35% (7/20) of controls, 89% (16/18, P < 0.001) in patients before and 72% (13/18, P < 0.03) after eradication. CGRP was positive in 40% (8/20) of controls, and in 100% (18/18, P < 0.001) of patients before and in 100% (18/18, P < 0.001) after eradication. The immune-staining of gastric mucosa for substance-P was positive in 25% (5/20) of healthy controls, and in 5.5% (3/18, P > 0.05) of patients before and in 0% of patients (0/18, P > 0.05) after H. pylori eradication. CONCLUSION: Distibution of TRVP1 and CGRP is altered during the development of H. pylori positive chronic gastritis. The immune-staining for TRVP1, CGRP and SP rwemained unchanged before and after H. pylori eradication treatment. The capsaicin-sensitive afferentation is an independent from the eradication treatment. The 6 wk time period might not be enough time for the restituion of chronic H. pylori positive chronic gastritis. The H. pylori infection might not represent the main pathological factor in the development of chronic gastritis.

Interaction between CTLA4 gene and IBD5 locus in Hungarian Crohn's disease patients.

BACKGROUNDS AND AIMS: The IGR2198a_1 and IGR2096a_1 variants of the IBD5 region were found to be associated with Crohn's disease (CD) in the Hungarian population, while IGR2230a_1 does not seem to confer risk for the disease. In the present study, our aim was to investigate the statistical interaction of these three IBD5 polymorphisms with the +49 A/G substitution within the cytotoxic T lymphocyte antigen-4 (CTLA4) gene, detected previously as neutral gene variant in Hungarian IBD patients. METHODS: A total of 305 unrelated subjects with CD and 310 healthy controls were genotyped with PCR-RFLP methods. RESULTS: In contrast with single gene effects, after genotype stratification, the IGR2198a_1 C and IGR2096a_1 T variants were found to confer susceptibility only in subjects with CTLA4 +49 AA genotype (P = 0.008; OR = 1.86 and P = 0.016; OR = 1.74, respectively), for IGR2230a_1 no such effect on disease risk could be demonstrated. CONCLUSION: Analysis of specific genotype combinations unfolded a possible association between the CTLA4 +49 A/G substitution and two of the observed IBD5 variants with respect to disease risk.

Serum prohepcidin levels in chronic inflammatory bowel diseases.

BACKGROUND AND AIMS: One of the major symptoms of chronic inflammatory bowel diseases is anemia. The two most common diseases are Crohn's disease and ulcerative colitis. Anemia may develop due to intestinal bleeding, iron absorption disturbances, or high levels of inflammatory cytokines. It is not clear whether or not hepcidin, the only known hormone regulating cellular iron uptake in mammals is involved. The transcription of hepcidin is controlled by the iron status of the body, hypoxia, and/or inflammation. This study was meant to find relationship between serum prohepcidin levels and clinical parameters of iron homeostasis or inflammatory state in patients suffering from Crohn's disease or ulcerative colitis. METHODS: Serum prohepcidin levels were measured with ELISA in 72 patients diagnosed with ulcerative colitis and 30 patients suffering from Crohn's disease. RESULTS: In both groups serum iron levels were lower, while levels of C-reactive protein were higher than in the healthy controls. Serum prohepcidin levels showed no significant differences compared to those in the control group. In the affected patients only weak correlations were observed between prohepcidin levels and diagnostic parameters: in Crohn's disease prohepcidin levels correlated positively with transferrin levels, total iron-binding capacity, transferrin saturation, activity index, and serum albumin levels, while in ulcerative coltitis prohepcidin levels were related to transferrin levels and transferrin saturation. CONCLUSION: It seems obvious that serum prohepcidin level determination in itself is not a satisfactory diagnostic or prognostic measure in anemia of chronic inflammatory bowel diseases.

Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn's disease patients.

AIM: To investigate the interaction of interleukin-23 receptor (IL23R) (rs1004819 and rs2201841), autophagy-related 16-like 1 (ATG16L1) (rs2241880), caspase recruitment domain-containing protein 15 (CARD15) genes, and IBD5 locus in Crohn's disease (CD) patients. METHODS: A total of 315 unrelated subjects with CD and 314 healthy controls were genotyped. Interactions and specific genotype combinations of a total of eight variants were tested. The variants of IBD5 locus (IGR2198a_1 rs11739135 and IGR2096a_1 rs12521868), CARD15 (R702W rs2066845 and L1007fs rs2066847), ATG16L1 (rs2241880) and IL23R (rs1004819, rs2201841) genes were genotyped by PCR-RFLP, the G908R (rs2066844) in CARD15 was determined by direct sequencing. RESULTS: The association of ATG16L1 T300A with CD was confirmed [P = 0.004, odds ratio (OR) = 1.69, 95% CI: 1.19-2.41], and both IL23R variants were found to represent significant risk for the disease (P = 0.008, OR = 2.05, 95% CI: 1.20-3.50 for rs1004819 AA; P < 0.001, OR = 2.97, 95% CI: 1.65-5.33 for rs2201841 CC). Logistic regression analysis of pairwise interaction of the inflammatory bowel disease (IBD) loci indicated that IL23R, ATG16L1, CARD15 and IBD5 (IGR2198a_1) contribute independently to disease risk. We also analysed the specific combinations by pair of individual ATG16L1, IL23R rs1004819, rs2201841, IGR2198a_1, IGR2096a_1 and CARD15 genotypes for disease risk influence. In almost all cases, the combined risk of susceptibility pairs was higher in patients carrying two different risk-associated gene variants together than individuals with just one polymorphism. The highest OR was found for IL23R rs2201841 homozygous genotype with combination of positive CARD15 status (P < 0.001, OR = 9.15, 95% CI: 2.05-40.74). CONCLUSION: The present study suggests a cumulative effect of individual IBD susceptibility loci.

Functional variants of glucokinase regulatory protein and apolipoprotein A5 genes in ischemic stroke.

Both the natural variants of the apolipoprotein A5 (APOA5) and the glucokinase regulatory protein gene (GCKR) have been shown to associate with increased fasting triglyceride levels. Here, we investigated the possible association of the functional variants of these two genes with non-fasting triglyceride levels and their susceptibility nature in ischemic stroke. A total of 513 stroke patients and 172 healthy controls were genotyped. All the APOA5 variants (T-1131C, IVS3 + G476A, C56G, and T1259C) were associated with increased triglyceride levels in all stroke patients and controls; except for T1259C, they all conferred risk for the disease. No such association was found for the examined GCKR rs1260326 (C1337T) variant. Furthermore, we examined the effects of specific combinations of the GCKR rs1260326 and APOA5 polymorphisms. Our findings confirmed the previous results regarding the association of APOA5 variants with triglyceride-level increase and stroke susceptibility of these alleles. By contrast, we could not detect any association of the studied GCKR allele with triglyceride levels or with the susceptibility of stroke in the same cohort of patients. In addition, the effect of APOA5 did not change significantly when specific combinations of the two genes were present.

[The value of twenty-four hour intraoesophageal pH monitoring and manometry in the management of patients with upper gastrointestinal symptoms]. / A 24 órás pH-monitorozás és a nyelocso-manometria szerepe felso gastrointestinalis panaszokkal jelentkezo betegek kivizsgálásában.

UNLABELLED: Functional gastroenterological examinations (intraoesophageal pH monitoring, oesophageal manometry, scintigraphy, impedance examination) play important role in the management of patients with upper gastrointestinal complaints. PATIENTS AND METHODS: Four different cases are demonstrated where diagnose and therapy was developed by these examinations. Two patients had typical gastro-oesophageal reflux symptoms and two others had dysphagia. Intraoesophageal pH monitoring was performed by Zinetics twenty-four hour one or two channel pH catheters and oesophageal manometry was carried out by Zinetics EMC four channel catheter with water perfusion method. CASE REPORTS: In one of the patients with typical and extraoesophageal reflux symptoms, lower oesophageal sphincter incompetency by manometry and pathological acid reflux was observed by intraoesophageal pH monitoring, respectively. Furthermore, hiatal hernia was established, peristalsis of the oesophagus proved to be preserved. Because of incomplete efficacy of proton pump inhibitor (PPI) therapy, antireflux surgery was indicated. An other patient with reflux symptoms had physiological pH monitoring and manometric values. Hypersensitive oesophagus was diagnosed and PPI therapy in double dose was applied. Both patients are symptom free up to now. Other two patients complained difficult swallowing and weight loss. Absence of lower oesophageal sphincter relaxation and hypomotility of the oesophagus was observed. After oesophageal dilatation, both patients with achalasia could easy swallow and eat. CONCLUSIONS: Our cases confirm the importance of the twenty-four hour intraoesophageal pH monitoring and oesophageal manometry in the diagnosis of gastro-oesophageal reflux disease, non-cardiac chest pain, other extraoesophageal manifestations and dysphagia. These examinations support the decision for the adequate therapeutic strategy (conventional treatment, surgery or operation or endoscopic intervention) and are important in the follow-up of patients.

[Possible role of selected IGR and SLC22A4/SLC22A5 loci in development of inflammatory bowel diseases]. / Az 5q31 IBD5-régióban található IGR és SLC22A4/SLC22A5 variánsok lehetséges szerepe a gyulladásos bélbetegség kialakulásában.

UNLABELLED: The IBD5 locus (MIM#606348) on chromosome 5q31 has been demonstrated to confer increased risk for inflammatory bowel disease. Controversial reports have been published about the significance of individual loci located in this region. Here we investigated the possible genetic association of inflammatory bowel diseases with C1672T of SLC22A4 and G-207C SLC22A5 alleles, and with IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility variants of the IBD5 region located on chromosome 5q31. PATIENTS AND METHODS: Total of 440 patients, 206 with Crohn's disease, 234 with ulcerative colitis, and 279 controls were studied by PCR-RFLP methods. RESULTS: Neither the C1672T, and G-207C alleles, nor the TC haplotype were found to confer risk for Crohn's disease or ulcerative colitis. By contrast, both of the minor allele frequencies of IGR2096a_1 T (48.1%) and IGR2198a_1 C (46.1%) were increased in Crohn's disease subjects as compared with the controls (38.5% and 38.4%, respectively; p<0.05). Using regression analysis adjusted to age and gender these alleles were found to confer risk for Crohn's disease (OR=1.694, 95% CI: 1.137-2.522; p=0.010 for T allele, OR=1.644, 95% CI=1.103-2.449; p=0.015 for C allele of IGRs). In UC no such associations were found. CONCLUSIONS: Our results revealed the susceptibility nature of the examined IGR minor alleles in Hungarians, which nation differs historically from the surrounding Caucasian populations in origin of the founders of the state.

Interethnic differences of CYP2C9 alleles in healthy Hungarian and Roma population samples: relationship to worldwide allelic frequencies.

CYP2C9 gene polymorphisms are widely studied in several ethnic groups, however they are less known in the Roma population. The aim of this work was to study the ethnic differences of the CYP2C9 allele distribution in a healthy Roma population in order to compare them with a healthy Hungarian population. A total of 535 Hungarian and 465 Roma volunteers were genotyped for the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) allelic variants by PCR-RFLP assay. The frequencies of the CYP2C9*1, *2 and *3 alleles in the Hungarian population were 0.787, 0.125, and 0.088 and in Roma 0.727, 0.118, and 0.155, respectively. We found a significant difference in CYP2C9*3 prevalence between the Hungarian and Roma populations, which have therapeutic consequences (p<0.005). The distribution of *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3 genotypes in Hungarians were 0.620, 0.195, 0.139, 0.021, 0.015, and 0.011, while in Roma were 0.533, 0.168, 0.219, 0.011, 0.047, and 0.022, respectively. A significant difference was found between the Hungarian and Roma populations regarding the *1/*1, *1/*3 and the *2/*3 (p<0.005) genotypes. This is the first study to investigate the polymorphisms of CYP2C9 gene in the two largest populations in Hungary, healthy Hungarians and Roma. The prevalence of variant CYP2C9 alleles in the Hungarian population is similar to that observed in other European populations. In contrast, the Roma population differs from Hungarians, from most of other Caucasian groups, and from Indians in the incidence of CYP2C9 common variants. The difference in allele distribution patterns between the two populations studied has therapeutic implications as it influences the optimization of therapies.

Vitamin K epoxide reductase complex 1 (VKORC1) haplotypes in healthy Hungarian and Roma population samples.

The aim of this work was to determine the VKORC1 haplotype profile in healthy Hungarian and Roma population samples, and to compare our data with other selected populations. Using haplotype tagging SNPs (G-1639A, G9041A and C6009T), we characterized Hungarian (n = 510) and Roma (n = 451) population samples with regard to VKORC1*1, *2, *3 and *4 haplotypes. In the Hungarian samples, the VKORC1*1, *2, *3 and *4 haplotypes accounted for 3, 39, 37 and 21%, respectively and by contrast, in the Roma population samples the VKORC1 variants were 5, 30, 46 and 19%, respectively. Comparing the genotypes of Roma and Hungarian populations, difference was found in the *2/*2 (6.87 vs 13.5%), *2/*4 (13.9 vs 19.2%) and *3*3 (21.9 vs 13.7%) VKORC1 haplotype combinations. Comparing each group with the others, and our data with findings published previously by other groups, the VKORC1 genetic profile in Hungarians was more similar to European Caucasians and Americans with European descent than to Roma samples. Clear differences could be detected between Roma versus Hungarians and European or American Caucasians; the Roma population had only minor similarities with data from India.

IGR2096a_1 T and IGR2198a_1 C alleles on IBD5 locus of chromosome 5q31 region confer risk for Crohn's disease in Hungarian patients.

BACKGROUND AND AIMS: We investigated the possible association of IBD with C1672T of SLC22A4 and G-207C of SLC22A5 alleles, and with the novel IGR2096a_1 (rs12521868) and IGR2198a_1 (rs11739135) susceptibility loci, all located on IBD5 locus of chromosome 5q31. MATERIALS AND METHODS: DNA of 217 Crohn's disease, 252 ulcerative colitis, and 290 control patients were analyzed by polymerase chain reaction/restriction fragment length polymorphism methods. RESULTS: Neither the C1672T and G-207C alleles, nor the TC haplotype were found to be risk factors. By contrast, the minor allele frequencies of IGR2096a_1 T (47.2%) and IGR2198a_1 C (45.9%) were increased in Crohn's disease compared with the controls (38.2% and 37.7%, respectively; p < 0.05); multivariate regression analysis revealed a risk nature for Crohn's disease (OR = 1.748, 95% CI 1.186-2.574; p = 0.007 for T allele, OR = 1.646, 95% CI 1.119-2.423, p = 0.011 for C allele of IGRs). CONCLUSION: The data suggest a special haplotype arrangement of susceptibility genes at the IBD5 locus in Hungarians, which nation differs historically from the surrounding Caucasian ethnicities in its origin.

No association of the cytotoxic T-lymphocyte associated gene CTLA4 +49A/G polymorphisms with Crohn's disease and ulcerative colitis in Hungarian population samples.

AIM: The goal of the current work was to analyse the prevalence of the +49A/G variant of the cytotoxic T-lymphocyte antigen 4 gene (CTLA4) in Hungarian patients with Crohnos disease (CD) and ulcerative colitis (UC). METHODS: A total of 130 unrelated subjects with CD and 150 with UC, and 170 matched controls were genotyped for the single nucleotide polymorphism (SNP). The genotypes were determined by using PCR/RFLP test. RESULTS: The G allele frequency and the prevalence of the GG genotype were 38.1% and 12.3% in the CD group, 40.6% and 18.6% in the UC patients, and 37.4% and 15.9% in the control group, respectively. CONCLUSION: The results of the current study show that carriage of the +49G SNP in heterozygous or in homozygous form does not confer risk either for CD or for UC in the Hungarian population.

Prevalence of SLC22A4 1672T and SLC22A5 -207C combination defined TC haplotype in Hungarian ulcerative colitis patients.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. The aim of this study was to verify the prevalence rate of the haplotype called TC, determined by combination of two functional alleles of OCTN cation transporter genes (SLC22A4 1672T and SLC22A5 -207C combination variants) in ulcerative colitis patients and unrelated healthy controls. The "TC haplotype" has recently been suggested to confer risk for UC. A total of 121 unrelated Hungarian subjects with UC and 110 matched controls were genotyped for the two single nucleotide polymorphisms. The genotypes were determined by using PCR/RFLP assay and direct sequencing. The SLC22A4 1672T allele frequency was 46.7% in the patients with UC and 46.4% in the controls, whereas the SLC22A5 -207C allele occurred in 48.8% of the patients and 51.4% of the controls. The prevalence of the TC haplotype was 19% in the patient group and 22.7% in controls. Since there was no accumulation of the TC haplotype in the patient group, our observation suggests that carrying the TC haplotype is not associated with a higher risk for UC in the Hungarian population.

[Postinfectious irritable bowel syndrome]. / Posztinfekciós irritábilis bél szindróma.

Postinfectious irritable bowel syndrome (IBS) is a subgroup of IBS. Patients with an episode of bacterial gastroenteritis may have a 12-fold increased risk of developing IBS symptoms within the same year. The IBS can be manifested in each of its clinical types, but the diarrhea-predominant form occurs most commonly. The primary pathophysiologic factor in developing IBS after enteral infection may be defects in enteric nervous system which can produce abnormality in visceral hypersensitivity and intestinal motility. These patients also display exaggerated increases in mucosal immunocompetent T lymphocytes and an abnormally high pro- versus anti-inflammatory cytokine ratio, providing evidence to the contribution of the immune system in the development of postinfectious IBS. Via bi-directional brain-gut interactions both peripheral and central events can play a role in the development of clinical symptoms. Stress is associated with significant worsening of the complaints in IBS and may also result in a shift in the host-gut microbial relationship. IBS itself may predispose patients to acute bacterial gastroenteritis because of the altered intestinal motility. It needs further clarifying the relationship between IBS and small intestinal bacterial overgrowth syndrome. Upon the data so far the altered intestinal flora in IBS would merely reflect developments due to altered motility and not a causal relationship. The treatment of postinfectious IBS does not differ principally from that of the idiopathic IBS. Antibiotics or probiotics may lead to temporary symptomatic improvement, but, given the lack of evidence based data, they cannot be advised for routine use so far.