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sulcerations at ileocolonoscopy and a history of positive clinical response followed by second-ary failure and/or intolerance to at least one TNFα antagonist. Patients randomized in theTNF-K group were receiving TNF-K at days 0, 7, 28, 84 and placebo at days 91 and 112.Patients randomized in the control group were receiving placebo at days 0, 7, 28, and TNF-K at days 84, 91 and 112. TNF-K was injected intramuscularly at the dose of 180 mcg perinjection. The primary end point was CDAI clinical remission (CDAI≤150) at week 8. Otherefficacy end-points included mucosal healing at week 12 and evolution of calprotectin andC-reactive protein. Immune responses were evaluated through titration of anti-TNFα andanti-KLH antibodies. Results: All patients have been recruited. Fewmild or moderate transientlocal and systemic reactions have been recorded following immunizations. The only seriousadverse event reported by the investigator as potentially related to the study drug was adeterioration of CD one month following administration of blinded treatment. There wereno other safety concerns. Full analysis is ongoing. Conclusions: Active immunization withTNF-K in patients with Crohn's disease is safe. Full immunogenicity and clinical efficacyresults will be presented.

Su2092

Clinical Risk Stratification Predicts Development of Endoscopic RecurrenceAfter Crohn's Disease Surgery: Early Results From the POCER StudyPeter De Cruz, Michael A. Kamm, Amy L. Hamilton, Kathryn J. Ritchie, AlexandraGorelik, Danny Liew, Lani Prideaux, Ian C. Lawrance, Jane M. Andrews, Peter A.Bampton, Miles Sparrow, Simon Jakobovits, Timothy H. Florin, Peter R. Gibson, HenryDebinski, Richard B. Gearry, Finlay A. Macrae, Rupert W. Leong, Ian Kronborg, Susan J.Connor, Graham Radford-Smith, Warwick Selby, Michael J. Johnston, Rodney Woods,James Keck, Richard Brouwer, William Connell, Steven J. Brown, Sally Bell, Mark Lust,Ross Elliott, Paul Desmond

Background: Smoking, perforating disease and prior resection(s) have been identified indi-vidually from retrospective cohort studies as clinical factors associated with an increasedrisk of earlier post-operative recurrence of Crohn's disease. Therapies such as anti-TNFcannot be applied prophylactically to all patients due to their high cost and poor risk-benefitratio in some patients. Identification of patients at risk of recurrence would be of great clinicaland economic value in tailoring post-operative therapy. We aimed to assess prospectively riskfactor assessment, drug treatment according to risk, and endoscopy 6 months after surgery.Methods: All patients undergoing “curative” resection for CD received post-operatively 3months of metronidazole at 400mg bd. High risk patients (smoker, perforating disease orprior resection) also received thiopurine (azathioprine 2mg/kg or 6 mercaptopurine 1.5mg/kg). High risk patients intolerant of thiopurine received adalimumab 160mg, 80mg andthen 40mg two weekly. All patients were assessed clinically, with CDAI, CRP and withileocolonoscopy 6 months post-operatively. Endoscopic recurrence was assessed using theRutgeert's score (0 = no lesions, i1 = mild small superficial anastomotic lesions, i2 - i4 =moderate to severe lesions). Results: Sixty-nine high risk patients (52% male, median age40 years) and 15 low risk patients (33% male, median age 37 years were studied. Of thehigh risk patients 25 (36%) were smokers, 46 (67%) had perforating disease and 30 (44%)had undergone prior resection. Twenty-six (38%) had more than 1 high risk factor. Of thelow risk patients, at 6 months, endoscopic remission (Rutgeerts i0 or i1) was observed in11 (73%) patients. Of the high risk patients on thiopurine at 6 months endoscopic remissionwas observed in 30 (60%) patients. Of the high risk patients on adalimumab at 6 monthsendoscopic remission was observed in 17 (94%) patients. The positive predictive value of1, 2 and 3 risk factors for determining endoscopic recurrence at 6 months was 0.28, 0.35and 0.33 respectively. Conclusions: Risk stratification based on clinical risk factors is largelyable to predict those who go on to develop endoscopic recurrence. Only about one quarterof low risk patients on minimal therapy had endoscopic recurrence. A higher proportionof high risk patients, despite being on thiopurine, developed recurrence. Adalimumab inthis setting appeared more effective in preventing recurrence. Use of these prospectivelyvalidated clinical risk factors may therefore be useful in identifying those patients who areat greatest risk of earlier post-operative recurrence for whom a more intensive immunosup-pressive prophylactic regimen may be warranted.

Su2093

Post-Treatment Hemoglobin in the Fergi Study Cohort and the Risk of AnemiaRecurrence in IBDRayko Evstatiev, Janne Harjunpää, Tariq Iqbal, Marcel Felder, Christoph Gasche

BACKGROUND: Correction of IBD-associated anemia with intravenous iron is highly effect-ive; still, anemia recurs in 50% of patients within 10 months. The efficacy of a ferritin-triggered maintenance regimen with ferric carboxymaltose (FCM) after correction of anemiaby intravenous iron (FERGIcor study; Gastroenterology Sept. 2011) has been demonstratedin the placebo-controlled FERGImain study (UEGW 2011). Bi-monthly assessment of ferritinand FCM administration (500 mg if ferritin had dropped below 100 μg/L) prolonged timeto recurrence of anemia, compared to placebo (8 month anaemia free survival 73% vs. 60%;p=0.049). Nevertheless, in 36% of patients with apparently normal ferritin levels anemiarecurred within 8 months. Here we tested other prognostic factors than ferritin for theirability to predict recurrence of anemia. METHODS: 140 patients from FERGImain who didnot receive FCM (either randomized to placebo [n=99] or not receiving any treatment [n=41] as ferritin always >100 μg/l) were included in this analysis. Cox regression and Kaplan-Meier analyses were performed to identify predictors of anemia recurrence over the studyperiod of 8 months. The evaluated variables were: baseline levels of hemoglobin (Hb) (asg/dL above the lower limit of normal, i.e. 12 g/dL [women] and 13 g/dL [men]), ferritin,transferrin saturation (TSAT), transferrin, mean corpuscular volume (MCV), mean corpuscu-lar hemoglobin (MCH), reticulocyte counts, and C-reactive protein (CRP) as well as thechange of these variables over the 4 week period prior to baseline. RESULTS: Anemiarecurred in 54/140 patients within 8 months. Hb was the strongest predictor of anemiarecurrence (HR for an increase of one g/dL = 0.395, 95% CI 0.248-0.628, p<0.001). Thus,Hb levels close to the lower limit of normal were associated with higher risk of anemiarecurrence. Furthermore, low transferrin concentration (HR 0.451, 95% CI 0.229-0.891,p=0.022) and elevated CRP (HR 1.026, 95% CI 1.001-1.053, p=0.043) were associated with

S-568AGA Abstracts

faster recurrence of anemia. The remaining variables did not show statistically significantassociations with anemia recurrence. CONCLUSIONS: Our findings indicate that higherpost-treatment Hb levels protect from anemia recurrence in IBD. Thus, the target post-treatment Hb should be at least 1 g/dL above the lower limit of normal. In addition, lowtransferrin and high CRP may help identify patients at risk that may benefit from ironmaintenance treatment.

Mo1000

Association of High Risk Waist-to-HIP Ratio With Barrett's Esophagus, andTheir Interaction With Race/EthnicityJennifer R. Kramer, Lori A. Fischbach, Peter Richardson, David J. Ramsey, Abeer Alsarraj,Stephanie J. Fitzgerald, Yasser H. Shaib, Neena Abraham, Maria E. Velez, Rhonda A.Cole, Bhupinderjit S. Anand, David Graham, Hashem El-Serag

Background: Obesity may increase the risk of developing Barrett's esophagus (BE). However,the association between body mass index and BE has been tenuous at best. It has beensuggested that central adiposity may increase the risk of GERD and therefore play a significantrole in BE. Previous studies examining this issue have been conducted in mostly Caucasianpopulations. Therefore, we examined the effect that waist-to-hip ratio (WHR), a measurefor abdominal obesity, has on the risk for BE and determined if race/ethnicity and GERDsymptoms mediated this effect. Methods: We enrolled consecutive eligible patients scheduledfor an elective upper endoscopy at a large VA Medical Center during 2008-2011. We alsoenrolled patients being seen at the primary care clinic. All patients underwent an upper GIendoscopy with systematic recording of findings on suspected BE (Prague CM classification)and gastric mapping biopsies. Definitive BE was defined in the presence of specialized smallintestinal epithelium with goblet cells in biopsies obtained from suspected BE areas. Studyparticipants completed a computer assisted survey which ascertained the frequency andseverity of GERD symptoms as measured by the Gastroesophageal Reflux Questionnaire,lifetime history and current use of alcohol, and physical activity. Height, weight and waistand hip circumference were measured, and BMI and WHR were calculated. WHR wascategorized into high (≥0.9 for males and ≥0.85 for females) and low categories as donein previous studies. Data were analyzed with logistic regression models while controllingfor confounders that were identified by a directed acyclic graph. These included variablessuch as age, H. pylori infection, current alcohol drinking, and physical activity. Results:There were 237 cases with definite BE, 1020 controls from the endoscopy clinic, and 479controls from the primary care clinic. The mean age was 60.5 years and 57.9% were non-Hispanic white, 33.2% African American, 6.4% Hispanic, and 2.5% other race. The majorityof patients had a high-risk WHR (85.4%). In multivariate logistic regression, patients witha high WHR were 2.5 times more likely to have BE than patients with a lower WHR (95%CI:1.4-4.3). The estimated effect of high WHR on BE was strongest for non-Hispanic whites(OR=2.23; 95%CI: 1.1-4.6); while there was no observed effect of high WHR on BE amongBlacks (OR=1.17; 95%CI: 0.4-3.7) or among Hispanics (OR=0.7; 95%CI: 0.1-5.1). AddingGERD symptoms to themodel did not change themagnitude of these associations appreciably.Conclusions: High waist-to-hip-ratio is associated with a significant increase in the riskof BE. This effect was not mediated by GERD symptoms and was only evident in non-Hispanic whites.

Mo1001

Prevalence of Anal Incontinence Among Norwegian Women, a Cross-SectionalStudy (Hunt 3)Kathrine Rommen, Berit Schei, Astrid Rydning, Siv Mørkved

AIMS OF THE STUDY: Anal incontinence is a symptom associated with age, bowel symptomsand obstetric injuries. Aim of the study was to establish the prevalence of anal incontinenceamong women and the impact on daily life. Secondary aims were to study associationsbetween anal incontinence and bowel symptoms and health related factors such as age andbody mass index (BMI). MATERIAL ANDMETHODS: The study is a part of a cross-sectional,large community-based survey (HUNT 3) conducted in Nord-Trøndelag, Norway. Data werecollected through interviews, questionnaires and clinical examinations. In total 40 955community-dwelling women (aged 30+) were invited to participate. All eligible womenattending the research centres received a questionnaire (Q2) containing a section about analincontinence. Anal incontinence was defined as involuntary loss of feces and/or flatus weeklyor more. Fecal and flatal incontinence was defined as involuntary loss of feces and flatusweekly or more, respectively. Statistical methods included tests of association and logisticregression analysis. Data were analysed using SPSS v 17. RESULTS: A total of 25 037 womenaged 30+ participated in HUNT 3, giving a response rate of 61.1%. Questionnaire 2 (Q2)was returned by 24 738 of the participants. In Q2, the section including anal incontinencewas completed by 20 391 (82.4%) of the responders. Non-responders and responders tothe anal incontinence section did not differ significantly on background data available, non-responders were excluded from further analysis. Among the 20 391 women included in thestudy, anal incontinence was reported by 19.3% (95%CI 18.7-19.8). In total, 3.0% (95%CI2.8-3.2) of the women reported fecal incontinence ≥weekly, 18.6% (95%CI 18.1-19.1)reported leakage of gas ≥weekly. Lack of ability to defer defecation for 15 minutes wasexperienced by 2 586 women (13.7%, 95%CI 13.2-14.2). Among women with anal incontin-ence, 794 (26.0%, 95%CI 24.4-27.5) stated it had impact on daily life. Increasing agewas associated with anal and fecal incontinence (table 1). Menopause and BMI≥35 weresignificantly associated with anal incontinence, daily smoking was associated with fecalincontinence. Lack of ability to defer defecation for 15 minutes, diarrhea, mixed diarrhea/constipation, nausea and heartburn were significantly associated with both anal and fecalincontinence, constipation was associated with anal incontinence. CONCLUSION: Prevalenceof anal incontinence in the study population was 19.3%, fecal incontinence 3.0%. The studyconfirms that anal and fecal incontinence are age-related conditions. Several bowel symptomsare significantly associated with anal and fecal incontinence, diarrhea and lack of abilityto defer defecation for 15 minutes are the variables strongest associated with anal andfecal incontinence.Table 1. Prevalence and odds ratios (OR) for variables associated with anal and fecal incontin-ence.

* = significant at p<.05 Bivariate analyses are adjusted for age, except age.

Mo1002

Weight Loss Reduces Gastroesophageal Reflux Symptoms: A ProspectivePopulation-Based Cohort Study, the Hunt StudyEivind Ness-Jensen, Anna P. Lindam, Jesper Lagergren, Kristian Hveem

Introduction Heartburn and acid regurgitation are the typical gastroesophageal reflux symp-toms (GERS). GERS are associated with reduced health related quality of life, esophagitis,and adenocarcinoma of the esophagus. High body mass index (BMI) is a known risk factorof GERS. However, the effect of weight loss on GERS is not clear. Aims and methods Theaim of the study was to clarify the effect of weight loss on GERS. The study was part of apopulation-based cohort study in Nord-Trøndelag County, Norway (the HUNT study),where all adult residents of the county were invited to participate. Between HUNT 2 (1995-1997) and HUNT 3 (2006-2009) 29610 individuals (61% response rate) were prospectivelyfollowed-up, and the participants reported complaints with GERS through written question-naires at both time points. In addition, a wide range of other health related topics were assessedthrough questionnaires, and clinical examinations were performed by trained personnel. Therisk of losing GERS by decrease in BMI between HUNT 2 and HUNT 3 was calculated bylogistic regression. The analyses were stratified by use of antireflux medication (proton pumpinhibitors, H2-receptor antagonists, or antacids) and the results were adjusted for sex,age, cigarette smoking status, frequency of alcohol consumption, length of education, andfrequency of physical exercise. Results Of the 9299 persons with any GERS (minor or severecomplaints) in HUNT 2, 2398 (26%) reported no complaints in HUNT 3, i.e. loss of anyGERS. Among those with >3.5 units reduction of BMI, the odds ratio (OR) of loss of anyGERS was 1.98 (95% confidence interval (CI) 1.45-2.72; p-value for trend <0.001) comparedto those with stable BMI (<0.5 units change) if they used less than weekly antirefluxmedication or no antireflux medication, and 3.95 (95% CI 2.03-7.65; p-value for trend<0.001) if they used at least weekly antireflux medication (Table). Of the 1553 persons withsevere GERS in HUNT 2, 284 (18%) reported no complaints in HUNT 3, i.e. loss of severeGERS, and the respective ORs were 0.90 (95% CI 0.32-2.55; p-value for trend 0.189) and3.11 (95% CI 1.13-8.58; p-value for trend 0.047; Table). Conclusion Since weight lossseems to reduce GERS dose-dependently and increase the beneficial effect of antirefluxmedication, it should be considered in the treatment of GERD.Table Odds ratio (OR) and 95% confidence interval (CI) of loss of gastroesophageal refluxsymptoms (GERS) by change in body mass index (BMI) and use of antireflux medication,adjusted for sex, age, cigarette smoking, alcohol consumption, education, and physical exer-cise.

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Mo1003

Medical Treatments and Risk Factors for Resection Surgery in Crohn'sDisease: Results From the Swiss IBD Cohort StudyValérie Pittet, Gerhard Rogler, Pierre F. Michetti, Nicolas Fournier, John-Paul Vader, AlainSchoepfer, Christian Mottet, Florian Froehlich

Background: Surgery has been previously reported to be necessary in up to 80% of Crohn'sdisease (CD) patients, and up to 65% of patients needed reoperation after 10 years. Preventionof surgery is therefore a particularly important issue for these patients. Treatment optionsare controversial and data on them are scarce. This study reports medical treatments andmain clinical risk factors in CD patients having undergone one or several surgeries. Risksfor being free from surgery were also assessed. Methods: Retrospective cohort study, usingdata from patients included in the Swiss IBD cohort study from November 2006 to July2011. History of resective surgeries, clinical characteristics and drug regimens were collectedthrough detailed medical records. Univariate and multivariate analyses for clinical andtherapeutic factors were performed. Cox regression was made to estimate free-of-surgeryrisks for different phenotypes and drugs. Results: Out of 1138 CD patients in the cohort,721 (63.4%) were free of surgery at inclusion; 203 (17.8%) had 1 surgery and 214 (18.8%)>1 surgery.Main risk factors for surgerywere disease duration 5-10 years (OR=2.92; p<0.001)and >10 years (OR=10.45; p<0.001), as well as stricturing (OR=8.33; p<0.001) or fistulizingdisease (OR=7.34; p<0.001). Risk factors for repeated surgery was disease duration >10years (OR=2.55; p=0.006) or fistulizing disease (OR=3.79; p<0.001). At inclusion, 107patients (25.7%) had at least one anti-TNF alpha, 168 (40.3%) at least one immunosuppress-ive agent, and 41 (9.8%) at least 5-ASA or antibiotics. 64 (15.3%) were not exposed to anymedical treatment. Kaplan-Meier curves showed that the risk of being free of surgery was65% after 10 years, 42% after 20 years and 23% after 40 years. Surgical risks were fourresp. five time higher for fistulizing and stricturing phenotypes (Hazard ratio (HR) =4.2;p<0.001; resp. HR=4.7; p<0.001) compared to inflammatory phenotype. Surgical risk was4 times lower (HR=0.27; p=0.063) in CD patients under anti-TNF alpha compared to thoseunder other or no drugs. Conclusion: The risk of having resective surgery was confirmedto be very high for CD in our cohort. Duration of disease, fistulizing and stricturing diseasepattern enhance the risk of surgery. Anti-TNF alpha tends to lower this risk.

Mo1004

Is There an East-West Gradient in the Incidence of IBD in Europe? andFurther Far East in China? First Results From the Epicom StudyJohan Burisch, Bing Xia, Silvija Cukovic-Cavka, John Kaimakliotis, Dana Duricova, OlgaShonova, Ida Vind, Natalia Pedersen, Ebbe Langholz, Niels Thorsgaard, Vibeke Andersen,Jens F. Dahlerup, Riina Salupere, Kári R. Nielsen, Pia Manninen, Epameinondas V.Tsianos, Karin Ladefoged, Einar Bjornsson, Yvonne Bailey, Selwyn H. Odes, MatteoMartinato, Limas Kupcinskas, Svetlana I. Turcan, Fernando Magro, Adrian Goldis, ElenaBelousova, Vicent Hernandez, Sven Almer, Jonas Halfvarson, Naila Arebi, Shaji Sebastian,Peter L. Lakatos, Pia S. Munkholm

Background: The incidence of inflammatory bowel disease (IBD) is traditionally low inEastern Europe, it has however recently become more prevalent in i.e. Hungary and Croatia.The reason for these changes remains unknown. This study was initiated in 32 centers from14 Western and 8 Eastern European countries and 1 Asian country to investigate whetherthere is an east-west-gradient in Europe in the incidence of IBD and if the difference isbeing caused by environmental factors. Methods: A new prospective, uniformly diagnosedby international diagnostic criteria controlled by the web registration, population-basedinception cohort of adult and pediatric patients diagnosed with IBD in 2010 and followedup until 1.1 2012 was created. Patients were included during a one-year period, 1.1.2010-31.12.2010 and entered in the web-based database, www.epicom-ecco.eu, constructed bythe epidemiologist and HD-Support Inc1. Audit in 23 centers was carried out to secure dataconsistency among centers. Results: In total 1625 patients aged 15 years or more wereidentified, of whom 876 (54%) were diagnosed as ulcerative colitis (UC), 556 (34%) asCrohn's disease (CD), and 192 (12%) as indeterminate (IC). The center specific incidencerates are shown in table 1. The overall incidence per 100.000 of IBD in Europe was 15.0;UC 8.0, CD 5.2 and IC 1.9. The mean incidence rates for IBD, CD and UC of the WesternEuropean centers were more than two times higher than the Eastern European centers (IBD:18.6 vs. 7.7; UC: 9.7 vs. 4.4; CD: 6.2 vs. 3.1; IC: 2.7 vs. 0.2). The Chinese incidence rateswere for IBD 1.4, for UC 0.9, for CD 0.4 and for IC 0.0. For IBD and UC the highestreported incidences were on the Faroe Islands (84.1 and 31.5) and for CD, Hungary (11.1).The lowest incidence of IBD as well as UC overall was in Wuhan, China (1.4 and 0.9) andin Europe in Romania (4.1 and 2.4), and of CD in Greenland (no cases of CD). Almostall cases of IC (96%) came from Western European centers indicating differences in theinterpretations of the used diagnostic criteria. The median number of days from onset ofsymptoms to diagnosis was 90 (Range: 0-11208) for Western Europe, 86 (Range: 0-7188) forEastern Europe and 120 (Range: 7-10790) for Wuhan, China. Conclusion: These preliminaryresults of the first web-based inception cohort trial suggest an East-West gradient in theincidence of IBD in Europe. Both UC and CD are much more common in Western Europe,and the rate of IC was higher than predicted. IBD remains rare in China. 1 Burisch J et al.Construction and validation of a web-based epidemiological database for inflammatory boweldiseases in Europe. An EpiCom study. JCC 5 (2011), pp. 342-349Incidence rates (/100 000) of cases aged 15 years or over for inflammatory bowel disease,ulcerative colitis, Crohn's disease and indeterminate colitis.

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