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P235 PREVALENCE AND DETERMINANTS OF PSC IN A COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND NORMAL LIVER FUNCTION TESTS
74 P234 IS THERE AN ASSOCIATION BETWEEN C-REACTIVE PROTEIN LEVEL AND INFLIXIMAB DEPENDENCY IN CROHN' S DISEASE? A DCCD, DANISH CROHN COLITIS DATABASE STUDY V. Giannelli, D. Duricova, N. Pedersen, M. Elkjaer, P. Munkholm. Herlev University Hospital, Taastrup, Denmark Aim: To assess the role of C-reactive protein (CRP) as a predictor in longterm response of infliximab (IFX) therapy in patients with Crohn' s disease (CD). Patients and methods: 91 CD patients from the DCCD treated with IFX from 1999 till 2006 were included: 38 males, median age 34 years (16-66), median disease duration 6 years (0-33), in total treated with 559 IFX infusions, median 4 (1-28). The indication of IFX therapy was luminal and fistulazing disease in 60 and 31 patients respectively. The CRP level before the 1st IFX infusion was measured, level < 10mg/l was considered normal. The clinical outcome was evaluated according to Copenhagen phenotype model of IFX dependency (1,2): 1. Immediate response (IR) was evaluated 30 days after the 1st infusion: Complete response (CR); Partial response (PR); No response (NR) 2. Long-term response (LTR) ≤ 90 days after the last intended IFX: Prolonged (PRO): Maintenance of CR/PR; IFX dependency (ID): Relapse of symptoms after ending IFX requiring repeated IFX to regain CR/PR or repetitive IFX therapy > 1 year to sustain CR/PR; No response (NR) Mann-Whitney and Cruscal-Wallis tests were used to compare the differences in CRP levels. P<0.05 was considered statistically significant. Results: 77 (85%) patients obtained immediate response (45 CR, 32 PR). In LTR 32 (35%) patients became PRO, 41 (45%) became ID and 18 (20%) NR. There was no significant difference in mean CRP (mg/l) level before the 1st IFX infusion between immediate responders and non-responders (23, 8 vs. 18.1, p=0.43). Similarly, we did not find any association between CRP level at baseline and long-term response to IFX (PRO 21.2, ID 26.8 and NR 17.0, p= 0.21). Conclusion: Our results show that CRP is not a predictive factor neither in immediate outcome nor in long-term infliximab response. No association was revealed in infliximab dependent patients. References: 1. Wewer V. JPGN 2006; 42:40-5. 2. Pedersen N. GUT 2006 (abstract) Suppl Nov, vol 55, A 130.
P235 PREVALENCE AND DETERMINANTS OF PSC IN A COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND NORMAL LIVER FUNCTION TESTS H.K. Bungay 1 , O.C. Buchel 2 , S.P.L. Travis 2 , F. Cummings 2 , R.W.G. Chapman 2 . 1 Radiology Department, John Radcliffe Hospital, Oxford, United Kingdom; 2 Gastroenterology Department, John Radcliffe Hospital, Oxford, United Kingdom Introduction: PSC is the most frequent hepatobiliary disease associated with ulcerative colitis(UC), and is diagnosed in 2-4% of cases. Alkaline phosphatase is usually elevated, but may be normal. Magnetic resonance cholangiography (MRC) is now the usual method for diagnosing PSC. The prevalence of PSC in patients with IBD and normal liver enzymes is unknown. Aims and methods: To investigate the prevalence and potential determinants of PSC in patients with IBD and normal liver enzymes. Patients with extensive colitis and normal liver enzymes were recruited from the IBD clinic and consented to an MRC. Demographic, lifestyle, medical and laboratory data were collated retrospectively. 9 healthy volunteers with normal liver enzyme levels, had MRC examinations as a control group. Continuous variables (age, disease duration) were compared using Student' s t-test. Other variables (gender, smoking status, azathioprine and extra intestinal manifestations) were analysed by the chi-squared test. Results: All MRCs in the control group were normal. The study group of 32 men (63%) and 19 women (37%) was aged 18-84 yr (median 48). 45 had panUC, 2 Crohn' s colitis, 2 right sided colitis, 1 distal colitis and 1 pancolitis yet to be classified. Of the 51 patients, 9 (18%) had biliary abnormalities consistent with PSC on MRC. There was no difference between the mean age of patients with and without PSC (53.4 vs 48.4yr, p=0.435)and nor did duration of IBD differ significantly (17.7 vs 12.0 years, p=0.390). The prevalence of PSC in women was 6/19 (32%) and 3/32 (9%) in men (p=0.053, OR for males 0.22, 95% CI 0.05 to 1.04). 2/4 (50%) of active smokers had PSC compared to 6/41 (16%) of non- or ex- smokers (ns, p=0.624). 2/19 (11%) of those treated with azathioprine had PSC, compared to 7/28 (25%) of those never receiving AZA (p=0.197). 5/19 (26%) patients with extra intestinal manifestations had PSC, compared to 3/26 (12%) without (p=0.188). No patient has yet had a liver biopsy. Conclusion: 18% patients with normal liver enzymes and colitis had appearances consistent with PSC on MRC. There was a strong trend for more females, and weaker trend for those with EIMs or those naïve to AZA to have
Poster Presentations the appearances of PSC. This study suggests that PSC may be more prevalent than appreciated in patients with IBD.
P236 ASSOCIATION OF β-DEFENSIN 1 SINGLE NUCLEOTIDE POLYMORPHISMS WITH CROHN' S DISEASE P.L. Lakatos 1 , K.A. Kocsis 2 , F. Somogyvari 2 , P. Fuszek 1 , J. Papp 1 , S. Fischer 1, T. Szamosi 1 , L. Lakatos 3 , A. Kovacs 4 , P. Hofner 2 , Y. Mandi 2 . 1 Semmelweis University, Budapest, Hungary; 2 University of Szeged, Szeged, Hungary; 3 Csolnoky F. County Hospital, Veszprem, Hungary; 4 Peterfi Hospital, Budapest, Hungary Background: It has been suggested that deficient defensin expression is connected with the chronic inflammation of Crohn' s disease. The regional localization of the Crohn' s disease, ileal or colonic disease can be linked to different defensin profiles. As constitutive β-defensin 1 has a colonic expression, we considered it of interest to investigate single nucleotide polymorphisms (SNPs) of the β-defensin 1 gene (DEFB1) in Crohn' s disease. Methods: Three SNPs of the DEFB1 gene DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946) were genotyped either by Custom TaqMan® SNP Genotyping Assays or by restriction fragment length polymorphisms (RFLP) in 190 patients with Crohn' s disease and 95 Hungarian controls. Results: Strong associations between the G-20A and C-44G SNPs and the colonic, and ileocolonic localization of the disease, respectively, but no association was detected as concerns the ileal localization. A significantly higher frequency of the GA genotype of G-20A was observed among patients with colonic localization (60%) as compared with the healthy controls, (39%), with OR 2.39. The GG genotype of C-44G SNP, which can be regarded as a protective genotype, was much frequent (4%) among the patients than among the controls (12%), OR 3.367. Conclusions: These results indicate that genetic variations in the DEFB1 gene encoding constitutive human β-defensin 1 may associated to the risk for Crohn' s disease and may determine disease phenotype, e.g. colonic localization
P237 INTERACTION BETWEEN SEROREACTIVITY TO MICROBIAL ANTIGENS AND GENETICS IN CROHN' S DISEASE: IS THERE A ROLE FOR DEFENSINS? P.L. Lakatos 1 , I. Altorjay 2 , Y. Mandy 3 , J. Tumpek 2 , K. Palatka 2 , L. Lakatos 4 , A. Kovacs 5 , T. Molnar 3 , P. Miheller 1 , T. Szamosi 1 , M. Papp 2 . 1 Semmelweis University, Budapest, Hungary; 2 University of Debrecen, Debrecen, Hungary; 3 University of Szeged, Szeged, Hungary; 4 Csolnoky F. County Hospital, Veszprem, Hungary; 5 Peterfi Hospital, Budapest, Hungary Background: Antibodies to different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn' s disease (CD). Recently an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in different genes other then NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Methods: 376 well-characterized, unrelated, consecutive CD patients (m/f:191/185, age at onset: 29.1±12.9years, duration:7.9±11.7years) were investigated. Sera were assayed for anti-Omp, ASCA IgA and IgG and antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by PCR-RFLP. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. Results: The carriage of DEFB1 20A variant alleles less frequently led to anti glycan positivity, when compared with patients without (29.6% vs. 46.2%, OR: 0.49, 95%CI: 0.25-0.97). Similar tendency was observed for DEFB1 44G (with 21.6% vs without 10.2%, p=0.06) and ALCA. A gene or serology dosage effect was not observed. In contrast no association was found between the DEFB1 G52A, DLG5 R30Q and NOD1/CARD4 E266K variants and any of the serology markers. Conclusions: We found that variants in human b-defensin 1 gene are inversely associated with antibodies against glycan antibodies further confirming an important role for innate immunity in the pathogenesis of CD.
P235 PREVALENCE AND DETERMINANTS OF PSC IN A COHORT OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE AND NORMAL LIVER FUNCTION TESTS H.K. Bungay 1 , O.C. Buchel 2 , S.P.L. Travis 2 , F. Cummings 2 , R.W.G. Chapman 2 . 1 Radiology Department, John Radcliffe Hospital, Oxford, United Kingdom; 2 Gastroenterology Department, John Radcliffe Hospital, Oxford, United Kingdom Introduction: PSC is the most frequent hepatobiliary disease associated with ulcerative colitis(UC), and is diagnosed in 2-4% of cases. Alkaline phosphatase is usually elevated, but may be normal. Magnetic resonance cholangiography (MRC) is now the usual method for diagnosing PSC. The prevalence of PSC in patients with IBD and normal liver enzymes is unknown. Aims and methods: To investigate the prevalence and potential determinants of PSC in patients with IBD and normal liver enzymes. Patients with extensive colitis and normal liver enzymes were recruited from the IBD clinic and consented to an MRC. Demographic, lifestyle, medical and laboratory data were collated retrospectively. 9 healthy volunteers with normal liver enzyme levels, had MRC examinations as a control group. Continuous variables (age, disease duration) were compared using Student' s t-test. Other variables (gender, smoking status, azathioprine and extra intestinal manifestations) were analysed by the chi-squared test. Results: All MRCs in the control group were normal. The study group of 32 men (63%) and 19 women (37%) was aged 18-84 yr (median 48). 45 had panUC, 2 Crohn' s colitis, 2 right sided colitis, 1 distal colitis and 1 pancolitis yet to be classified. Of the 51 patients, 9 (18%) had biliary abnormalities consistent with PSC on MRC. There was no difference between the mean age of patients with and without PSC (53.4 vs 48.4yr, p=0.435)and nor did duration of IBD differ significantly (17.7 vs 12.0 years, p=0.390). The prevalence of PSC in women was 6/19 (32%) and 3/32 (9%) in men (p=0.053, OR for males 0.22, 95% CI 0.05 to 1.04). 2/4 (50%) of active smokers had PSC compared to 6/41 (16%) of non- or ex- smokers (ns, p=0.624). 2/19 (11%) of those treated with azathioprine had PSC, compared to 7/28 (25%) of those never receiving AZA (p=0.197). 5/19 (26%) patients with extra intestinal manifestations had PSC, compared to 3/26 (12%) without (p=0.188). No patient has yet had a liver biopsy. Conclusion: 18% patients with normal liver enzymes and colitis had appearances consistent with PSC on MRC. There was a strong trend for more females, and weaker trend for those with EIMs or those naïve to AZA to have
Poster Presentations the appearances of PSC. This study suggests that PSC may be more prevalent than appreciated in patients with IBD.
P236 ASSOCIATION OF β-DEFENSIN 1 SINGLE NUCLEOTIDE POLYMORPHISMS WITH CROHN' S DISEASE P.L. Lakatos 1 , K.A. Kocsis 2 , F. Somogyvari 2 , P. Fuszek 1 , J. Papp 1 , S. Fischer 1, T. Szamosi 1 , L. Lakatos 3 , A. Kovacs 4 , P. Hofner 2 , Y. Mandi 2 . 1 Semmelweis University, Budapest, Hungary; 2 University of Szeged, Szeged, Hungary; 3 Csolnoky F. County Hospital, Veszprem, Hungary; 4 Peterfi Hospital, Budapest, Hungary Background: It has been suggested that deficient defensin expression is connected with the chronic inflammation of Crohn' s disease. The regional localization of the Crohn' s disease, ileal or colonic disease can be linked to different defensin profiles. As constitutive β-defensin 1 has a colonic expression, we considered it of interest to investigate single nucleotide polymorphisms (SNPs) of the β-defensin 1 gene (DEFB1) in Crohn' s disease. Methods: Three SNPs of the DEFB1 gene DEFB1 G-20A (rs11362), DEFB1 C-44G (rs1800972) and DEFB1 G-52A (rs1799946) were genotyped either by Custom TaqMan® SNP Genotyping Assays or by restriction fragment length polymorphisms (RFLP) in 190 patients with Crohn' s disease and 95 Hungarian controls. Results: Strong associations between the G-20A and C-44G SNPs and the colonic, and ileocolonic localization of the disease, respectively, but no association was detected as concerns the ileal localization. A significantly higher frequency of the GA genotype of G-20A was observed among patients with colonic localization (60%) as compared with the healthy controls, (39%), with OR 2.39. The GG genotype of C-44G SNP, which can be regarded as a protective genotype, was much frequent (4%) among the patients than among the controls (12%), OR 3.367. Conclusions: These results indicate that genetic variations in the DEFB1 gene encoding constitutive human β-defensin 1 may associated to the risk for Crohn' s disease and may determine disease phenotype, e.g. colonic localization
P237 INTERACTION BETWEEN SEROREACTIVITY TO MICROBIAL ANTIGENS AND GENETICS IN CROHN' S DISEASE: IS THERE A ROLE FOR DEFENSINS? P.L. Lakatos 1 , I. Altorjay 2 , Y. Mandy 3 , J. Tumpek 2 , K. Palatka 2 , L. Lakatos 4 , A. Kovacs 5 , T. Molnar 3 , P. Miheller 1 , T. Szamosi 1 , M. Papp 2 . 1 Semmelweis University, Budapest, Hungary; 2 University of Debrecen, Debrecen, Hungary; 3 University of Szeged, Szeged, Hungary; 4 Csolnoky F. County Hospital, Veszprem, Hungary; 5 Peterfi Hospital, Budapest, Hungary Background: Antibodies to different microbial epitopes are associated with disease phenotype, may be of diagnostic importance and may reflect a loss of tolerance in Crohn' s disease (CD). Recently an association was reported between the presence of these antibodies and mutations in pattern receptor genes. Our aim was to investigate whether mutations in different genes other then NOD2/CARD15 or TLR4 associated with CD (NOD1/CARD4, DLG5 and DEFB1) may influence the presence of antibodies against bacterial proteins and carbohydrates in a Hungarian cohort of CD patients. Methods: 376 well-characterized, unrelated, consecutive CD patients (m/f:191/185, age at onset: 29.1±12.9years, duration:7.9±11.7years) were investigated. Sera were assayed for anti-Omp, ASCA IgA and IgG and antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA), laminaribioside (ALCA), chitobioside (ACCA), and mannobioside (AMCA). NOD1/CARD4, DLG5 and DEFB1 variants were tested by PCR-RFLP. Detailed clinical phenotypes were determined by reviewing the patients' medical charts. Results: The carriage of DEFB1 20A variant alleles less frequently led to anti glycan positivity, when compared with patients without (29.6% vs. 46.2%, OR: 0.49, 95%CI: 0.25-0.97). Similar tendency was observed for DEFB1 44G (with 21.6% vs without 10.2%, p=0.06) and ALCA. A gene or serology dosage effect was not observed. In contrast no association was found between the DEFB1 G52A, DLG5 R30Q and NOD1/CARD4 E266K variants and any of the serology markers. Conclusions: We found that variants in human b-defensin 1 gene are inversely associated with antibodies against glycan antibodies further confirming an important role for innate immunity in the pathogenesis of CD.