Ulcerative Colitis: Lakatos PL

Lakatos PL. · No affiliation provided · World J Gastroenterol. · Pubmed #19370774 links to  free full text

Abstract: 5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azobond pro-drugs, as well as delayed- and controlled-release forms of mesalazine. However, poor adherence due to frequent daily dosing and a large number of tablets has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine, including the unique multi-matrix delivery system and mesalazine granules, were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of a low pill burden and might contribute to increased long-term compliance and treatment success in clinical practice. This editorial summarizes the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

Lakatos PL, Lakatos L. · No affiliation provided · World J Gastroenterol. · Pubmed #18609676 links to  free full text

Abstract: The risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this change is unknown; it may partly be explained by the more widespread use of maintenance therapy and surveillance colonoscopy.

Lakatos PL, Szamosi T, Lakatos L. · No affiliation provided · World J Gastroenterol. · Pubmed #18069751 links to  free full text

Abstract: Smoking is an important environmental factor in inflammatory bowel disease (IBD), having different effects in ulcerative colitis (UC) and Crohn's disease (CD). A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing CD and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves CD. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases.

Lakatos PL. · 1st Department of Medicine, Semmelweis University, Koranyi str. 2/A, H-1083, Hungary. · World J Gastroenterol. · Pubmed #17036379 links to  free full text

Abstract: Inflammatory bowel disease (IBD) is traditionally considered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemiologic studies are needed to better define the burden of illness, explore the mechanism of association with environmental factors, and identify new risk factors.

Lakatos PL, Lakatos L. · Semmelweis Egyetem, Altalános Orvostudományi Kar I. Belgyógyászati Klinika Budapest Korányi S. 2/A 1083. · Orv Hetil. · Pubmed #19228568 links to  free full text

Abstract: 5-aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents is commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once-daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once-daily mesalazine formulations.

Lakatos PL, Lakatos L. · 1st Department of Medicine, Semmelweis University, Koranyi S 2A, H-1083 Budapest, Hungary. · Pharmacol Res. · Pubmed #18801439 No free full text.

Abstract: 5-Aminosalicylate (5-ASA) agents remain the mainstay treatment in ulcerative colitis (UC). A number of oral 5-ASA agents are commercially available, including azo-bond pro-drugs such as sulfasalazine, olsalazine and balsalazide, and delayed- and controlled-release forms of mesalazine. In addition, the effectiveness of oral therapy relies on good compliance, which may be adversely affected by frequent daily dosing and a large number of tablets. Furthermore, poor adherence has been shown to be an important barrier to successful management of patients with UC. Recently, new, once daily formulations of mesalazine including the unique multi-matrix delivery system and mesalazine granules were proven to be efficacious in inducing and maintaining remission in mild-to-moderate UC, with a good safety profile comparable to that of other oral mesalazine formulations. In addition, they offer the advantage of low pill burden and may contribute to increased long-term compliance and treatment success in clinical practice and might potentially further contribute to a decline in the risk for UC-associated colon cancers. In this systematic review, the authors summarize the available literature on the short- and medium-term efficacy and safety of the new once daily mesalazine formulations.

Lakatos PL, Lakatos L. · Semmelweis Egyetem, Altalános Orvostudományi Kar I. Belgyógyászati Klinika Budapest Korányi S. u. 2/A 1083. · Orv Hetil. · Pubmed #18467261 links to  free full text

Abstract: The most important factors that determine treatment strategy in ulcerative colitis (UC) are disease extent and severity. Orally-topically administered 5-aminosalicylates (5-ASA) remain the treatment of choice in mild-to-moderate UC. In contrast, the treatment of refractory (to steroids, azathioprine or 5-ASA) and fulminant cases is still demanding. New evidence supports a role for infliximab induction and/or maintenance therapy in these subgroup of patients leading to increased remission and decreased colectomy rates. The aim of this paper is to review the rationale for the use of TNF-alpha inhibitors in the treatment of UC.

Lakatos PL, Lakatos L. · Semmelweis University, First Department of Medicine, H1083 Budapest, Koranyi S 2A, Hungary. · Expert Opin Pharmacother. · Pubmed #18345952 No free full text.

Abstract: BACKGROUND: Ulcerative proctitis (UP) is a common presentation of ulcerative colitis (UC). OBJECTIVE: To summarize available literature on up-to-date management and pharmacotherapy of UP patients. METHODS: Extensive Medline/Embase literature search was performed to identify relevant articles. RESULTS/CONCLUSION: Topical medication with rectally administered 5-aminosalicylic acid (5-ASA)/corticosteroid suppositories or enemas is effective treatment for most UP patients. Locally administered 5-ASA is more efficacious than oral compounds. The combination of topical 5-ASA and oral 5-ASA or topical steroids should be considered for escalation of treatment. Maintenance treatment is indicated in all UC cases. 5-ASA suppositories are suggested as first-line maintenance therapy if accepted by patients, although oral 5-ASA as maintenance therapy might prevent proximal extension of the disease. After re-assessment, chronically active patients refractory or intolerant to 5-ASAs and corticosteroids may require immunomodulators or biological therapy. Exceptional cases may require a proctocolectomy.

Lakatos L, Lakatos PL. · Csolnoky Ferenc Megyei Kórház I. Belgyógyászati Osztály Veszprém. · Orv Hetil. · Pubmed #17573252 No free full text.

Abstract: There are fewer significant changes in the medical therapy of ulcerative colitis (UC) compared to Crohn's disease. The most important factors that determine therapy are disease extent and severity. 5-aminosalicylates (5-ASA) constitute the treatment of choice in mild-to-moderate UC. The efficacy of new compounds (e.g. mesalazine) is only mildly improved compared to sulphasalazine; however, their use has become more frequent due to a more favorable side effects profile. Topical medication is more effective in proctitis and distal colitis, and the combination of topical and orally-administered drugs is superior to oral therapy alone also in extensive disease. Thus, this latter regimen should be considered for cases where the escalation of treatment is required. Systemic steroids still represent the first line therapy in acute, severe UC, while in patients who do not respond to steroids, cyclosporine and infliximab should be considered as a second line therapy and as alternatives for colectomy. Maintenance treatment is indicated in all UC cases. 5-ASA compounds are suggested as first line maintenance therapy with the optimal dose still being under investigation. Topical compounds are effective also for maintenance in distal colitis or proctitis, if accepted by the patients. Immunosuppressives, especially azathioprine, should be considered in chronically active, steroid dependent or resistant patients. According to recent publications, azathioprine is almost equally effective in UC and CD. The question of chemoprevention is important during maintenance. There are increasing data supporting the notion that aminosalicylates may lower the risk for UC-associated colorectal cancer. The most important changes in the management of UC are the more frequent use of topical aminosalicylates and azathioprine, the availability of infliximab in severe UC, and increasing use of aminosalicylates for chemoprevention of colorectal carcinoma. Furthermore, adequate attention is needed to better organize the patient-doctor relationship and for greater adherence to medical therapy.

Papp M, Altorjay I, Lakatos PL. · Debreceni Egyetem, Orvos- és Egészségtudományi Centrum Belgyógyászati Intézet, Gasztroenterológiai Tanszék, Debrecen. · Orv Hetil. · Pubmed #17478404 No free full text.

Abstract: The panel of serologic markers for inflammatory bowel diseases (IBDs) is rapidly expanding. Although anti- Saccharomyces cerevisiae antibodies (ASCA) and atypical perinuclear antineutrophil cytoplasmic antibodies (atypical P-ANCA) remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. Such antibodies include anti-OmpC (outer membrane porin C), anti- Pseudomonas fluorescens (anti-I2) and antiglycan antibodies (anti-laminaribioside carbohydrate antibody [ALCA]), anti-chitobioside carbohydrate antibody [ACCA]), anti-mannobioside carbohydrate antibody [AMCA]) and anti-CBir1; this latter is the first bacterial antigen to induce colitis in animal models of IBD and also leads to a pathological immune response in IBD patients (anti-flagellin antibody). The role of assessment of various antibodies in the current diagnostic algorithm of IBD is rather questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is getting more into the focus of interest. An increasing number of observations confirm that patients with Crohn's disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease (e.g. stricture and/or perforation) and are at higher risk for surgery than those without, or with low titer of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.

Lakatos L, Lakatos PL. · Csolnoky Ferenc Kórház, I. Belgyógyászati Osztály, Veszprém, Hungary. · Orv Hetil. · Pubmed #17344143 No free full text.

Abstract: Significant changes have been observed in the epidemiology of inflammatory bowel diseases (IBD) in the last two decades. Traditionally, the incidence of IBD was higher in the developed, industrialized countries, in contrast, nowadays it became more prevalent in the previously low incidence areas. In particular, the incidence of ulcerative colitis (UC) is similar to that observed in North America and Western Europe, while the incidence of Crohn's disease (CD) in developing countries is still low, suggesting that the environmental factors may act faster or differently in UC than in CD. In Europe, the North to South gradient disappeared, and also the West to East gradient is diminishing. Smoking and appendectomy may be considered as important environmental factors in both UC and CD, however, with opposite effects. In addition, the use of oral contraceptives is associated to disease susceptibility in both diseases. The role of diet, perinatal events, stress and nonsteroidal anti-inflammatory drugs in the pathogenesis is still controversial.

Lakatos L, Lakatos PL. · 1st Department of Medicine, Csolnoky F Province Hospital, Veszprem, Hungary. · Postgrad Med J. · Pubmed #16679472 links to  free full text

Abstract: Limited data are available on the frequency of inflammatory bowel diseases in East European countries. A recent study from Hungary reported an increasing incidence rate for ulcerative colitis (from 1.6 to 11.0) and for Crohn's disease (from 0.4 to 4.7) from 1977 to 2001. A similar trend was seen in Croatia. In contrast, other countries (for example, Czech Republic, Poland, Romania, Slovakia, and Baltic countries) reported low incidence and prevalence rates. This review will discuss the available data on the epidemiology of inflammatory bowel diseases in Eastern Europe, as well as consider the possible factors responsible for the differences seen between countries and epidemiological trends.

Lakatos PL, Fischer S, Lakatos L, Gal I, Papp J. · 1st Department of Medicine, Semmelweis University, Koranyi str. 2/A, H-1083 Budapest, Hungary. · World J Gastroenterol. · Pubmed #16609988 links to  free full text

Abstract: The pathogenesis of inflammatory bowel disease (IBD) is only partially understood. Various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity. Some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. This review addresses recent advances in the genetics of IBD. The article discusses the current information on the crosstalk between microbial and genetic factors (e.g. NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help in understanding the pathogenesis of IBD and can identify a number of potential targets for therapeutic intervention. In the future, genetics may help more accurately diagnose and predict disease course in IBD.

Lakatos L, Lakatos PL. · 1st Department of Medicine, Csolnoky F Province Hospital, Veszprem, Hungary. · Postgrad Med J. · Pubmed #16597815 links to  free full text

Abstract: Limited data are available on the management of inflammatory bowel diseases (IBD) in East European countries. The diagnostic tools and most treatment options are also available in Eastern Europe. The diagnostic procedures commonly used became more sophisticated in the past few years, with a greater use of computed tomography/magnetic resonance imaging and serology testing; however, double contrast barium enema, enteroclysis, and endoscopy remained standard. The medical therapy and surgical strategies are also somewhat different from those applied in Western countries. In ulcerative colitis, besides mesalazine, the use of sulphasalazine is still frequent, while azathioprine is only used in a minority of patients. The use of conventional corticosteroids is common and the rate of non-colorectal cancer associated colectomies is low. In contrast, 5-aminosalicylates are still used for maintenance in Crohn's disease and azathioprine is generally less frequently given compared with Western Europe. Biological agents have also become available about five years ago, yet their use is restricted mainly to specialised centres.

Lakatos PL, Gyori G, Halasz J, Fuszek P, Papp J, Jaray B, Lukovich P, Lakatos L. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · World J Gastroenterol. · Pubmed #15637769 links to  free full text

Abstract: The authors report the case of a 60-year-old male patient. In November 2001 he developed intestinal symptoms of bloody diarrhea and abdominal pain. Colononoscopy and biopsy established the diagnosis of ulcerative colitis (proctosigmoiditis). The disease activity was moderate at the beginning. No significant laboratory alterations were found (including CEA, CA19-9), and mesalazine was started orally. He was in remission until November 2003, when he was admitted to our Outpatient Clinic for upper and right lower abdominal pain and bloody diarrhea. Colonoscopy found proctosigmoiditis with a moderate activity, gastroscopy revealed chronic gastritis, laboratory data was normal. Treatment was amended with mesalazine clysma and methylprednisolone (16 mg) orally. Symptoms ameliorated; however, right lower abdominal pain persisted. US and CT examination demonstrated a pericecal cystic mass (11 cm x 3.5 cm). At first pericecal abscess was suspected, as the previous US examination (6 mo earlier) had revealed normal findings. Fine needle aspiration was performed. Cytology confirmed the diagnosis of mucocele. The patient underwent partial cecum resection and extirpation of the mucocele. He recovered well and the final histology revealed a cystadenoma of the appendix. Follow up was started. The patient is now free of symptoms. Although primary adenocarcinoma of the appendix is uncommon, the authors emphasize that preoperative diagnosis of an underlying malignancy in a mucocele is important for patient management; however, it is difficult on imaging studies.

Lakatos L, Lakatos PL. · Csolnoky Ferenc Kórház, I. sz. Belgyógyászati Osztály, Veszprém. · Orv Hetil. · Pubmed #14596023 No free full text.

Abstract: The pathogenesis of IBD is only partly understood; various environmental and host (e.g. genetic-, epithelial-, immune and non-immune) factors are involved. It is a multifactorial polygenic disease with probable genetic heterogeneity, some genes are associated with IBD itself, while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD) or are associated with disease location and/or behaviour. The role of environmental factors, in particular, enteric antigens, smoking and non-steroid anti-inflammatory drug use has been well established. However uptil now no proof of a role of any unique pathogenic bacteria or special dietary and/or psychosocial factor has been identified. In this hypothesis, the disease may develop in a genetically predisposed host as a consequence of disregulated immune response to environmental, in particular, enteric antigens, resulting in a continuous immune-mediated inflammation (in CD predominantly Th-1, in UC a modified Th-2 mechanisms are involved) and not in tolerance. As a consequence, the permeability of mucosa and the antigen challenge increases, in contrast, the disregulated immune response is unable to downregulate the inflammatory process. This will result in a continuous inflammation and tissue damage. The pathogenesis of CD is thought to be mainly an antigen driven, T-lymphocyte dependent process, while in UC the role of epithelial factors and activated granulocytes are essential.

Papp M, Altorjay I, Lakos G, Tumpek J, Sipka S, Dinya T, Palatka K, Veres G, Udvardy M, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Hungary. · Clin Vaccine Immunol. · Pubmed #19193830 No free full text.

Abstract: No clear guidelines for indirect immunofluorescence (IIF) detection and interpretation of antineutrophil cytoplasmic antibodies (ANCA) have been proposed for inflammatory bowel diseases (IBD). We evaluated the reliability of the combined use of ethanol- and formalin-fixed neutrophil substrates to identify atypical perinuclear ANCA (P-ANCA) by IIF under routine laboratory circumstances. A total of 204 IBD patients were assessed with four different fluorescent substrates in two distinct laboratories. Antibodies against myeloperoxidase, proteinase-3, and other specific granule proteins (elastase, lactoferrin, cathepsin G, lysozyme, and bactericidal permeability-increasing protein) were measured by an enzyme-linked immunosorbent assay. The combined application of ethanol- and formalin-fixed slides to detect atypical P-ANCA resulted in a lack of agreement between assays (kappa, < or =0.39) in the interassay study and moderate agreement in the interobserver study (kappa, 0.42). After atypical and typical P-ANCA patterns were combined, the consensus improved greatly. A total of 26.9% of patients were P-ANCA positive by at least two tests (44.3% of ulcerative colitis [UC] and 13.1% of Crohn's disease [CD] patients; P < 0.0001), while overall ANCA positivity was 22.5% to 34.8%. The combined application of ethanol-fixed and formaldehyde-fixed neutrophil substrates did not facilitate differentiation between P-ANCA and atypical P-ANCA, and the results were not consistent when substrates from different sources were used. Combining all P-ANCA ensures the highest sensitivity and specificity in differentiating UC from CD.

Lakatos PL, Altorjay I, Szamosi T, Palatka K, Vitalis Z, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Barta Z, Stocker W, Papp J, Veres G, Papp M, Anonymous00019. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Inflamm Bowel Dis. · Pubmed #18972554 No free full text.

Abstract: BACKGROUND: Pancreatic autoantibodies (PAB) and goblet cell autoantibodies (GAB) are specific for Crohn's disease (CD) and ulcerative colitis (UC), but the sensitivity alone is low. Conventional antibodies and carbohydrates (glycans) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Our aim was to determine the accuracy of PAB and GAB autoantibodies as well as to study relevant phenotype-serotype associations. METHODS: A Hungarian study cohort of 1092 subjects, including 689 well-characterized, unrelated IBD patients (CD: 579, m/f ratio: 274/305, duration: 7.9 +/- 11.2 years; UC: 110, m/f ratio: 53/57, duration: 8.9 +/- 9.8 years), 139 celiac patients, 100 healthy, and 64 non-IBD gastrointestinal controls were investigated. Sera were assayed for PAB-GAB IgA/IgG, anti-Omp, anti-Saccharomyces cerevisiae antibodies (ASCA), and anti-glycans. TLR4 and NOD2/CARD15 was tested by polymerase chain reaction / restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined. RESULTS: The prevalence of PAB was significantly more frequent in CD (41.1%) versus UC (22.7%), celiac (22.3%), and controls (8% and 4.6%, P < 0.01 for each), while GAB detection was poor in all groups except UC (15.4%). In CD the combination of PAB and/or anti-glycans/ASCA increased the sensitivity to 72% and 59%, respectively, for isolated colonic disease. PAB was associated to gylcans (odds ratio [OR] 1.74,P = 0.002), ASCA IgG/IgA (OR 1.75, P = 0.002), Omp (OR 1.86, P = 0.001) as well as perforating, perianal disease, arthritis, ocular, and cutaneous manifestations (P = 0.002-0.032). In contrast, PAB and GAB antibodies were not associated with NOD2/CARD15 or TLR4, response to medical therapy, or need for surgery. No associations were found in UC. CONCLUSIONS: PAB autoantibodies in combination with ASCA or anti-glycan antibodies increase the sensitivity for detecting CD, especially isolated colonic CD. Antibody response to PAB was associated with complicated disease phenotype and extraintestinal manifestations in this Eastern European IBD cohort.

Grundtner P, Gruber S, Murray SS, Vermeire S, Rutgeerts P, Decker T, Lakatos PL, Gasche C. · Division of Gastroenterology and Hepatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria. · Genes Immun. · Pubmed #18800073 No free full text.

Abstract: Genetic predisposition is a risk factor for the development of inflammatory bowel diseases (IBDs). Disruption of the interleukin (IL)-10 pathway in mice causes intestinal inflammation similar to human IBD. Two common non-synonymous IL-10R1 variants, S138G and G330R, were cloned and expressed in HeLa and Ba/F3. A reduction in IL-10-induced STAT1 and STAT3 activation was seen for IL-10R1-S138G (but not IL-10R1-G330R) by phosphospecific western blotting in both cell types. When analyzing 52 world populations for the presence of IL-10R1 variants, a strong dissimilarity was found between major geographical regions. In addition, when 182 IBD-parent trios were genotyped for both variants, a reduced transmission of haplotype -7 (carrying the S138G variant allele) to offspring with ulcerative colitis (UC) was observed. This UC-protective effect of S138G was confirmed in a Hungarian cohort (n=185, allele frequency 11.6 versus 17.5%; P=0.017) but not in an independent Belgian cohort (n=666, allele frequency 15.9 versus 15.5%; P=0.8). In conclusion, the IL-10R1 S138G variant is a loss-of-function allele for IL-10-induced STAT1 and STAT3 activation but does not protect from UC susceptibility.

Szamosi T, Lakatos PL, Anonymous00057, Szilvasi A, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Szabo O, Satori A, Tulassay Z, Miheller P, Horvath HC, Papp J, Tordai A, Andrikovics H. · 1st Department of Medicine, Semmelweis University, Koranyi st. 2/A, 1083, Budapest, Hungary. · Dig Dis Sci. · Pubmed #18716880 No free full text.

Abstract: PURPOSE: In previous studies the NFKBIA 3'UTR (untranslated region) AA genotype was associated with Crohn's disease (CD), while the NFKB1-94ins/delATTG mutation increased the risk for ulcerative colitis (UC). The aim of our study was to investigate these two polymorphisms and patients' response to medical therapy and/or disease phenotype in Hungarian inflammatory bowel disease (IBD) patients. METHODS: NFKBIA 3'UTR- and NFKB1-94ins/delATTG polymorphisms were investigated in 415 unrelated IBD patients (CD: 266 patients, mean age 35.2 +/- 12.1 years, duration 8.7 +/- 7.5 years; UC patients: 149, mean age 44.4 +/- 15.4 years, duration 10.7 +/- 8.9 years) and 149 controls by PCR-restriction fragment length polymorphism (RFLP) analysis. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The NFKBIA 3'UTR and NFKB1-94ins/delATTG genotypes and allele frequencies were not significantly different among IBD and controls. In patients with UC, the 3'UTR GG genotype was associated with extensive colitis (55.3 vs. 29.4%, odds ratio 2.97, 95% confidence interval 1.45-6.08). The presence of variant alleles did not predict response to steroids, infliximab, or need for surgery. CONCLUSIONS: The NFKBIA 3'UTR GG genotype was associated with an increased risk for extensive colitis in Hungarian patients. In contrast, variant alleles did not predict response to medical therapy or need for surgery.

Lakatos PL, Szamosi T, Szilvasi A, Molnar E, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Tulassay Z, Miheller P, Papp J, Tordai A, Andrikovics H, Anonymous00044. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Dig Liver Dis. · Pubmed #18499543 No free full text.

Abstract: BACKGROUND: North American and European genome-wide association scans have identified ATG16L1 and IL23R as novel inflammatory bowel disease (IBD) susceptibility genes and subsequent reports confirmed these findings in large independent populations. The aims of this study were to investigate the association and examine genotype-phenotype relationships in a Hungarian IBD cohort. METHODS: 415 unrelated IBD patients (CD: 266, age: 35.2+/-12.1 years, duration: 8.7+/-7.5 years and UC: 149, age: 44.4+/-15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were investigated. IL23R Arg381Gln (R381Q, rs11209026) and ATG16L1 Thr300Ala (T300A, rs2241880) polymorphisms were tested using LightCycler allele discrimination method. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The association between IL23R rs11209026, ATG16L1 rs2241880 and CD was confirmed (OR(IL23R381Q): 0.38, 95% CI: 0.16-0.87; OR(ATG16L1300AA): 1.86, 95% CI: 1.04-3.40). No difference was found between patients with UC and either controls or CD. In CD, IL23R 381Gln heterozygosity was associated with inflammatory disease (70% vs. 34%, p=0.037), while disease restricted to the colon was more prevalent in patients with the ATG16L1 300Ala/Ala homozygosity (33.3% vs. 21.1%, p=0.036). In addition, carriage of the variant alleles did not predict response to steroids, infliximab or need for surgery. CONCLUSIONS: We confirmed that ATG16L1 and IL23R are susceptibility loci for CD in Hungarian CD patients. Further studies are needed to confirm the reported phenotype-genotype associations found in this study.

Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Norman GL, Szamosi T, Papp J, Anonymous00071, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. · Am J Gastroenterol. · Pubmed #18047543 No free full text.

Abstract: BACKGROUND: Antibodies to Saccharomyces cerevisiae (S. cerevisiae) (ASCA) and porin protein-C of Escherichia coli (anti-OmpC) are associated with disease phenotype and may be of diagnostic importance in inflammatory bowel diseases (IBD). Our aim was to determine whether a panel of new antibodies against bacterial proteins and carbohydrates could help differentiate among the various forms of IBD, and whether they were associated with particular clinical manifestations in a Hungarian cohort of IBD patients. METHODS: Six hundred fifty-two well-characterized, unrelated, consecutive IBD patients (CD [Crohn's disease] 557, men/women 262/295, duration 8.1 +/- 11.3 yr; ulcerative colitis [UC] 95, men/women 44/51, duration 8.9 +/- 9.8 yr) and 100 healthy and 48 non-IBD gastrointestinal (GI) controls were investigated. Sera were assayed for anti-OmpC and antibodies against a mannan epitope of S. cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the patients' medical charts. RESULTS: Sixty-six percent of the CD patients had at least one of the investigated antibodies. Among glycan antibodies, gASCA or the combination of gASCA and atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) was most accurate for differentiating between CD and UC. ASCA and gASCA assays performed similarly. Increasing amount and level of antibody responses toward gASCA, ALCA, ACCA, AMCA, and OmpC were associated with more complicated disease behavior (P < 0.0001) and need for surgery in CD (P= 0.023). A serological dosage effect was also observed. gASCA and AMCA antibodies were associated with NOD2/CARD15, in addition to a gene-dosage effect. No serotype-phenotype associations were found in UC. CONCLUSIONS: Antibody response to this new panel of serological markers was associated with complicated disease phenotype, NOD2/CARD15 genotype, and a need for surgery in this eastern European IBD cohort.

Cervený P, Bortlík M, Kubena A, Vlcek J, Lakatos PL, Lukás M. · Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Kralove, Charles University, Prague, Czech Republic. · Inflamm Bowel Dis. · Pubmed #17538983 links to  free full text

Abstract: BACKGROUND: The purpose of the study was to assess overall nonadherence to treatment among patients with Crohn's disease (CD) and ulcerative colitis (UC) in a single tertiary center. METHODS: A total of 177 patients were enrolled in this study (84 males, 93 females; 117 CD, 60 UC). Patients were interviewed about their nonadherent behavior and their answers were analyzed using factor analysis. Urine samples were collected from a subcohort of 47 patients treated by mesalamine to verify the presence of 5-ASA or its metabolites. RESULTS: Overall intentional nonadherence was reported by 38.9% of patients; 18.6% of the patients discontinued the treatment at least once. Intentional dose reduction was reported by 18% of patients; 14.7% of patients occasionally did not refill their medications on time. There were no differences in adherence between males and females, disease type, previous bowel surgery, or marital, smoking, and nonsmoking status. More than 38% of patients reported unintentional nonadherence. Factor analysis proved that nonadherence increased with a higher education level of the patients and decreased with older age. Adverse drug effects strongly contributed to nonadherence. Nonadherent patients were more likely to be chronically active or in relapse (tau = 0.212; P = 0.002). In the group of 47 patients whose urine was analyzed, 6 cases (12.7%) were negative for mesalamine or its metabolite. CONCLUSIONS: The overall intentional nonadherence with medical therapy is relatively high among IBD patients and should be taken into account when a patient's response to treatment is unsatisfactory. Therefore, problems of nonadherence should be discussed with all IBD patients.

Fischer S, Lakatos PL, Anonymous00281, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Szilvasi A, Tulassay Z, Osztovits J, Papp J, Demeter P, Schwab R, Tordai A, Andrikovics H. · 1st Department of Medicine, Semmelweis University, Budapest, Hungary. · Scand J Gastroenterol. · Pubmed #17505995 No free full text.

Abstract: OBJECTIVE: MDR1 (ABCB1), a member of the ATP-binding cassette (ABC) transporters, is an attractive candidate gene for the pathogenesis of inflammatory bowel diseases (IBD) and perhaps for response to therapy. Since limited data are available on MDR1 and ABCG2 polymorphisms in East European IBD patients, the aim of this study was to investigate ABCG2 and MDR1 variants and responses to medical therapy and/or disease phenotype in Hungarian patients. MATERIAL AND METHODS: A total of 414 unrelated IBD patients (Crohn's disease (CD): 265, age: 35.2+/-12.1 years, duration: 8.7+/-7.6 years and ulcerative colitis (UC): 149, age: 44.4+/-15.4 years, duration: 10.7+/-8.9 years) and 149 healthy subjects were investigated. ABCG2 G34A, C421A and MDR1 C3435T, G2677T/A single nucleotide polymorphisms (SNPs) were detected using real-time polymerase chain reaction (PCR). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The frequency of the ABCG2 and MDR1 SNPs was not significantly different among IBD, CD, UC patients and controls. There was no difference in risk for steroid resistance in CD patients carrying variant ABCG2 (19.6% versus non-carriers 18.4%, p=NS) or MDR1 3435T (CC: 22.2% versus CT/TT: 17.6%) alleles. In addition, carriage of the variant allele was not associated with disease phenotype, presence of extra-intestinal manifestations, smoking, response to infliximab therapy or the need for surgery. In UC, the carriage of variant ABCG2 alleles seemed to be preventive for arthritis (15.5% versus 31.7%, OR: 0.39, 95% CI: 0.16-0.98). CONCLUSIONS: MDR1 and ABCG2 SNPs were not associated with disease susceptibility or disease phenotype in Hungarian patients, and variant alleles did not predict the response to medical therapy or the need for surgery. Further studies are needed to clarify the association between the presence of ABCG2 variants and arthritis in UC.

Papp M, Altorjay I, Norman GL, Shums Z, Palatka K, Vitalis Z, Foldi I, Lakos G, Tumpek J, Udvardy ML, Harsfalvi J, Fischer S, Lakatos L, Kovacs A, Bene L, Molnar T, Tulassay Z, Miheller P, Veres G, Papp J, Anonymous00415, Lakatos PL. · 2nd Department of Medicine, University of Debrecen, Debrecen, Hungary. · Inflamm Bowel Dis. · Pubmed #17417801 links to  free full text

Abstract: BACKGROUND: Antibodies directed against Saccharomyces cerevisiae (ASCA), perinuclear components of neutrophils (pANCA), and porin protein C of Escherichia coli (anti-OmpC) are reported to be associated with disease phenotype and may be of diagnostic importance in inflammatory bowel disease (IBD). Since limited data are available from Eastern Europe, we assessed the above antibodies in Hungarian IBD patients. METHODS: In all, 653 well-characterized, unrelated consecutive IBD patients (Crohn's disease [CD]: 558, m/f: 263/295, duration: 8.1 +/- 10.7 years; ulcerative colitis [UC]: 95, m/f: 44/51, duration: 8.9 +/- 9.8 years) and 100 healthy subjects were investigated. Sera were assayed for anti-Omp and ASCA by enzyme-linked immunosorbent assay (ELISA) and ANCA by indirect immunofluorescence assay (IIF). TLR4 and NOD2/CARD15 variants were tested by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: Anti-Omp, ASCA, and atypical pANCA antibodies were present in 31.2%, 59.3%, and 13.8% of CD, 24.2%, 13.7%, and 48.5% of UC patients, and in 20%, 16%, and 5.6% of controls, respectively. ASCA and anti-Omp positivity were associated with increased risk for CD (odds ratio [OR](ASCA) = 7.65, 95% confidence interval [CI]: 4.37-13.4; OR(Omp) = 1.81, 95% CI: 1.08-3.05). In a logistic regression analysis, anti-Omp and ASCA were independently associated with ileal and noninflammatory disease, but not with a risk for surgery or response to steroids or infliximab. A serology dosage effect was also observed. ASCA and anti-Omp antibodies were associated with NOD2/CARD15, in addition to a gene dosage effect. No associations were found in UC. CONCLUSIONS: Serological markers were useful in the differentiation between CD and UC in an Eastern European IBD cohort. Reactivity to microbial components was associated with disease phenotype and NOD2/CARD15 genotype, further supporting the role of altered microbial sensing in the pathogenesis of CD.