and IBD remain unclear. CMV infection may predispose some individuals to develop IBD,exacerbate existing IBD, and it is uncertain whether CMV is pathologic or reflects colonizationof rapidly dividing, dysplastic or inflamed tissue.While prior studies have suggested increasedcolectomy and mortality rates in IBD patients with CMV and improved remission rates withantiviral treatment, the impact of the severity of CMV infection on clinical outcome has notbeen examined. AIM: To evaluate whether severity of CMV colitis is associated with clinicaloutcomes in IBD patients. METHODS: A search of Cedars-Sinai Pathology database usingthe criteria “CMV” with “IBD,” “Crohn's disease” or “Ulcerative colitis” was performed.Patients were stratified into three histologic groups: 1) no evidence of CMV, 2) “lightinfection” defined by positive CMV immunohistochemistry without viral inclusion bodieson H&E stain, and 3) “heavy infection” defined by presence of viral inclusion bodies onH&E. Control subjects are IBD patients matched for modified HBI index. Charts werereviewed for modified HBI, mortality and colectomy rates, length of stay, and CMV quantitat-ive serum PCR. RESULTS: CMV infection was found in 27 of 603 patients (4.5%) andassociated with a higher colectomy rate compared to controls (48% vs. 30%, p=0.04).Colectomy rates were higher in patients with “heavy” (52%) compared to “light” (37%)infection. Antiviral treatment was associated with a 34% absolute reduction in the colectomyrate of patients with heavy, but not light, CMV infection. Surprisingly, peripheral CMV PCRlevels were lower in patients requiring colectomy (avg 63 copies, n=11) compared to thosewho avoided surgery (avg 198 copies, n=11). Among all antiviral treated patients, colectomyrate was higher in subjects with lower (avg 100 copies, n=6) compared to higher (avg 218copies, n=10) peripheral CMV levels. CONCLUSIONS: Heavy CMV infection is associatedwith higher colectomy rates. Importantly, peripheral CMV PCR levels do not correlate withhistological CMV infection or colectomy rate. Antiviral treatment may be more effective inIBD patients with heavy CMV infection. This suggest that in IBD patients with heavy CMVinfection, the virus may contribute more to the active inflammatory process and symptompresentation, than in those with lower CMV burden, where the bulk of symptoms are likelydue to underlying severe IBD itself.

1005

Clostridium difficile and Inflammatory Bowel Disease: Has the DiseaseChanged in Severity From 1998 to 2007?Ashwin N. Ananthakrishnan, Emily L. McGinley, Kia Saeian, David G. Binion

Introduction: Clostridium difficile (C difficile) has emerged as an important pathogen inpatients with inflammatory bowel disease (IBD) and is associated with increased morbidityand mortality. Although studies have documented an increase in prevalence, none hasexamined the temporal change in severity of C difficile infection (CDI) complicating IBD.Methods: Using data from the Nationwide Inpatient Sample, a national hospitalizationdischarge database in the United States, we identified all IBD-related hospitalizations duringthe years 1998, 2004, and 2007 using diagnosis codes. We examined hospitalizations witha co-existing code for C difficile. We performed two separate analyses: (1) Comparison ofthe actual outcomes (in-hospital mortality, colectomy rate) of C difficile-IBD across the threeyears; and (2) Comparison of these outcomes in the C difficile-IBD cohort relative to thenon-C difficile IBD controls in each corresponding year. Results: There were an estimated1,998, 4,800, and 6,902 IBD hospitalizations associated with CDI during 1998, 2004 and2007 respectively accounting for 1.4%, 2.3% and 2.9% of all IBD hospitalizations nationwide(p<0.001). Hospitalization during 2007 was associated with two-fold greater odds of CDI(Odds ratio (OR) 2.15, 95% confidence interval (CI) 1.92-2.41). In analysis restricted tothe C difficile-IBD population, hospitalization in 2004 (OR 1.38, 95% CI 0.83-2.28) or 2007(1.15, 95% CI 0.72-1.84) was not associated with higher mortality or need for colectomycompared to 1998. However, compared to the non-C difficile IBD controls during each ofthe corresponding time periods, there was an increase in the relative mortality risk associatedwith C difficile from 1998 (OR 2.38, 95% CI 1.52-3.72) to 2004 (4.00, 95% CI 3.03-5.29)and 2007 (OR 3.38, 95% CI 2.66-4.29). Similarly, there was relative increase in totalcolectomy risk from 1998 (OR 1.39, 95% CI 0.81-2.37) to 2004 (OR 1.62, 95% CI 1.15-2.29) and 2007 (OR 2.51, 95% CI 1.90-3.34). Conclusion: There has been a temporalincrease nationwide in CDI complicating IBD hospitalizations. The actual rate of adverseoutcomes in C difficile-IBD patients has remained relatively constant during between 1998and 2007. However, the risk of mortality relative to the non-C difficile-IBD cohort appearsto have increased between 1998 and 2004, and the relative risk of colectomy has alsocontinued to till 2007.

1006

Prevalence of Clostridium difficile Infection in Patients With InflammatoryBowel Disease is Significantly Related With Treatment ModalityChristian D. Stone, Neil A. Accortt, Simon H. Magowan

Background: Previous studies have shown that Clostridium difficile infection (CDI) is increas-ing among patients with inflammatory bowel disease (IBD). Infection is often community-acquired (CA) and is especially prevalent in ulcerative colitis. Possible contributing factorsto this pattern of risk include immunosuppressive (IS) medications and severity of disease.This study investigated whether risk of CDI in IBD is related to medication use and exploreddifferences between CA and hospital-acquired (HA) CDI. Methods: We pooled data fromtwo large administrative health claims databases to conduct a retrospective cohort analysisto determine the prevalence of C. difficile in IBD (ICD-9: 008.45). Inclusion criteria were≧2 IBD diagnoses (ICD-9: 555.x or 556.x) within 15 months of each other and a minimumof 21 months continuous enrollment. Concurrent medication use was documented andcategorized into four exposure groups: 1) no drug exposure [during enrollment]; 2) 5-ASA only; 3) 5-ASA and IS, (includes steroids and/or azathioprine, 6-mercaptopurine,methotrexate and cyclosporine); and 4) IS only. All subjects were followed forward in timeuntil the occurrence of the first C. difficile event, date of total colectomy, end of captureperiod (June 30, 2008) or end of enrollment. CA C. difficile was defined as any case confirmedoutside of the hospital, within 48 hours of hospital admission, or at least 60 days after ahospital discharge. All other cases were defined as HA. The log-rank test was used todetermine statistical significance. Results: 55,707 IBD subjects met the inclusion criteria.45.7% were male and 55.1% had ulcerative colitis. The majority of subjects (52.1%) received

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a 5-ASA in combination with another therapy while 18.1% received a 5-ASA only. Theprevalence of CDI in the 5-ASA only group was significantly lower than in the 5-ASA + ISgroup (p<0.01) and the IS only group (p<0.01) (Table). When limiting the analysis to CAC. difficile cases (65.9%), the prevalence was still significantly lower in the 5-ASA only group.Conclusions: Among IBD patients, the prevalence of CA CDI was 2-fold greater than HACDI. IBD patients taking IS drugs were at increased risk for CDI. The lowest risk was seenamong patients who received only 5-ASA compounds.

*p<0.05 using 5-ASA only as the comparator group

1007

Incidence of Inflammatory Bowel Disease Following the Walkerton Outbreakof Waterborne Bacterial GastroenteritisJohn K. Marshall, Marroon Thabane, Amit X. Garg, William F. Clark, Paul Moayyedi,Stephen M. Collins

Background and Aim: Acute gastroenteritis has been suggested to increase subsequent riskof IBD. InMay 2000, contamination ofmunicipal water by E. coli 0157:H7 andCampylobacterspecies caused a large outbreak of acute gastroenteritis (GE) in Walkerton, Ontario. TheWalkerton Health Study (WHS) was initiated to study related long-term health outcomesincluding inflammatory bowel disease (IBD). Previous genetic analyses of this well-definedcohort have associated post-infectious irritable bowel syndrome (PI-IBS) in this cohort withdefects in innate immunity and barrier function. Methods: WHS participants were askedabout diagnoses of IBD during standardized annual interviews from 2002 to 2008. Primarycare physicians were also contacted to identify subjects with IBD and provide supportingmedical records. An independent adjudication committee confirmed the timing and detailsof each diagnosis. Prevalence of IBD was assessed among subjects who resided in theWalkerton postal code during the outbreak. Incidence was assessed in a cohort of Walkertonresidents with no prior diagnosis of Crohn's disease (CD) or ulcerative colitis (UC). Results:Among 3047 eligible WHS participants (54.7% female; mean age 36.8±22.6), 16 cases ofIBD were confirmed on review of records (9 CD, 6 UC and 1 indeterminate colitis). Norecords were available to confirm or refute an additional 41 self-reported diagnoses. Underthe conservative assumption that non-participants did not have IBD, the estimated crudeprevalence of confirmed IBD in Walkerton was 525.1/105 (295.4/105 for CD vs. 196.9/105

for UC). Excluding diagnoses made before the outbreak or in the first year of follow-up,the annual incidence of IBD among 2031 subjects with GE during the outbreak was 49.2/105 vs. 14.5/105 among 983 subjects who remained well (incidence rate ratio 3.39; 95%CI 0.21, 13.81). The incidence of CD among subjects with GE was 35.2/105, while that forUC was 7.0/105. Estimates of prevalence and incidence of CD exceed published Canadianpopulation-based rates1 (233.7/105 and 13.4/105 respectively). Conclusion: The overallprevalence and incidence of CD in Walkerton is elevated. Although there is a trend to anincreased incidence of IBD among residents who suffered acute GE during the outbreak, itis not statistically significant. 1Bernstein CN et al, Am J Epidemiol 2006;101:1559-1568Funded by the Ontario Ministry of Health and Long-Term Care and the Crohn's and ColitisFoundation of Canada (CCFC)

1008

No Increase in JC Viremia, Lymphocyte Count, or Circulating CD34+Hematopoietic Progenitor Cells After Treatment With Vedolizumab, aHumanized Monoclonal Antibody to α4β7 IntegrinAsit Parikh, Tim Wyant, David B. Clifford, Joseph R. Berger, Brian G. Feagan, Irving Fox,Catherine Milch

Introduction: α4β7-Integrin on subsets of B- and T-lymphocytes mediates lymphocytetrafficking to the gastrointestinal tract. Vedolizumab is a selective humanized monoclonalantibody that blocks migration of α4β7-expressing lymphocytes to the gastrointestinal tractby antagonizing α4β7-MAdCAM interactions. Progressive multifocal leukoencephalopathy(PML), a rare but potentially fatal CNS infection caused by JC virus, is associated with thedual α4β1/α4β7 integrin antagonist natalizumab. Although the pathogenesis of PML is notestablished, elevations in circulating JC virus, total lymphocytes, and circulating CD34+hematopoietic progenitor cells have been hypothesized to contribute to PML associated withnatalizumab. Thus it is important to determine whether treatment with a selective α4β7integrin inhibitor causes these same biological changes. Methods: JC viremia was assessedretrospectively (assay sensitivity threshold 30 copies/ml) using frozen serum samples collectedat 2 month intervals from 1038 subjects enrolled in 9 vedolizumab clinical trials, includingongoing blinded phase 3 studies. Proportions of circulating CD34+ cells were assessedlongitudinally via FACS analysis of total leukocytes and lymphocytes from normal individualswho received a single IV dose of vedolizumab 300 mg. Results and Discussion: Approximately800 subjects have received 1-19 doses of vedolizumab for up to 2.5 years. JC virus testingshowed no association between vedolizumab exposure and viremia. Overall incidence of JCviremia was <1%with 5 unique patients testing positive (30-800 copies/ml) with no persistentviremia. All subjects with a positive result before or while receiving vedolizumab had asubsequent negative result. Furthermore, the occurrence of viremia did not increase withexposure duration. These findings suggest that JC viremia in subjects receiving vedolizumab,many in combination with corticosteroids or immunomodulators, may represent a stochasticevent not influenced by vedolizumab exposure. Absence of lymphocytosis was demonstrated

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