- Email: [email protected]
Mo1247 Autoimmune Pancreatitis is Associated With Aggressive IBD
AGA Abstracts
infections (OR 1.16, p=0.023), and shock (OR 1.30, p=0.022). Obese IBD patients were also more likely to have pulmonary complications (OR 1.21, p=0.021). There was no difference in cardiovascular complications (OR 1.09, p=0.524), perforations (OR 1.04, p= 0.707), venous thromboembolism (OR 1.18, p=0.399), or death (OR 0.73, p=0.067) when comparing obese with non-obese IBD surgeries. Obese IBD hospitalizations had marginally shorter lengths of stay by 0.61 days (p=0.005), but the daily cost was higher by $1324 (p<0.001) compared with non-obese IBD hospitalizations. CONCLUSIONS: In this nationwide analysis, obese IBD patients had increased rates of several post-operative complications. Although the lengths of stay were similar, the daily cost of hospitalizations was higher among obese IBD patients.
Mo1246 Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Study Siddhant Yadav, Jithinraj Edakkanambeth Varayil, Natasha Kamal, William S. Harmsen, David A. Wetter, Mark Denis P. Davis, William J. Tremaine, Jean-Frederic Colombel, Edward V. Loftus Background and Aims: An association between hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) has been described, but the relation between the two diseases is not very well understood or documented. We sought to better quantify the relationship, if one is present, between these two conditions. Methods: A well-established population-based inception cohort of North American IBD patients diagnosed between 1970 and 2004 were followed through death, loss of follow-up or to December 31, 2011 for the diagnosis of HS. We documented the extent and severity of IBD, and the putative risk factors for HS such as smoking, obesity, skin cancers and depression. The Hurley stage I, II, or III, (limited to extensive) was noted as well as the area of involvement, treatment and recurrence. The cumulative incidence of HS after IBD diagnosis was estimated using the Kaplan-Meier method. Results: Our 1970-2004 cohort of IBD patients included a total of 678 patients. Median follow-up was 19.8 years (range, 0.15 - 43.4). Ten patients were diagnosed with HS. Of these, 9 were diagnosed after the occurrence of IBD. The cumulative probability of HS after IBD diagnosis is shown in Table 1. Eight were females; 4 patients had ulcerative colitis and 6 had Crohn's disease. In patients with Crohn's disease, all had internal fistulas. Eight patients were smokers, 3 had skin cancer, and 6 were obese and had depression. Five patients had other dermatoses such as actinic keratosis. One patient each had acne, pilonidal disease, internal malignancy and pyoderma gangrenosum. There was no family history of HS. Seven patients had a Hurley staging of II. Six patients each had lesions involving the axilla and groin, while 2 had chest involvement. Six patients were treated with antibiotics, 3 with corticosteroids, and 5 underwent surgery. There was recurrence of HS in 4 patients. The cumulative probability of recurrence of HS is listed in Table 2. Conclusion: HS is a rare but important complication of IBD, with up to 2 - 3% of patients developing HS over 30 years from diagnosis. Most patients with HS and IBD were females. Patients with UC and CD have a similar risk for HS. Recurrent disease after surgical excision is common. Cumulative Probability of HS after IBD diagnosis
Mo1244 Outcomes of Endoscopic Therapy of Luminal Strictures in Crohn's Disease Jithinraj Edakkanambeth Varayil, Edward V. Loftus, Nayantara Coelho Prabhu Background: There is limited data on efficacy of endoscopic management of strictures in Crohn's disease. At our tertiary referral center which has a large inflammatory bowel disease practice, we sought to describe the long term efficacy of endoscopic dilation of luminal strictures. Methods: We identified all patients with endoscopic dilation of Crohn's strictures between 1/1/1990 and 11/30/2013. We performed an IRB-approved retrospective review of a random sampling of 100 of these patients. Demographics, disease characteristics including medication use, endoscopic procedural details, and long term outcome including need for surgery were analyzed. Endoscopic success was defined as effacement of dilating balloon or ability to pass the scope through the stricture after dilation. Results: A total of 231 endoscopic stricture dilations were performed in 100 patients. The mean age was 52+14 years; 51% were male. The median follow-up duration was 5.1 (IQR 2.1-9.8) years. The median duration of Crohn's disease before the first dilation was 23 (IQR 12-33) years. 35% had ileal involvement, 28% ileo-colonic, and 25% colonic; 78% had had prior intestinal resections. The commonest medications at the time of dilation were anti-TNF agents (30%), Azathioprine (30%), or 5-ASAs (22%). Sigmoidoscopy or colonoscopy 199 (86%) was the commonest procedure. The commonest stricture locations were ileo-colonic anastomosis, colon, and ano-rectal junction in 98 (42%), 42 (18%), and 38 (16%) procedures, respectively. Fifty (22%) procedures had preceding radiographic imaging with CT enterography (56%) being the commonest type and patients were symptomatic at 204 (88%) procedures. 60 patients had only 1 endoscopic dilation, 16 patients had 2, 8 patients had 3, and 16 had more than 3 procedures. Conscious sedation was used in 195 (84%) procedures. The median initial diameter of the stricture was 9 (IQR 7-10)mm, and inflammation was seen at the stricture site in 86 (37%) procedures. Dilation was performed using a balloon in 192 (83%) procedures, with a median maximal balloon size of 15(IQR 14-18) mm; using Hegar or Savary dilators in 29 (13%) procedures, with a median maximal size of 16 (IQR 12-18)mm. The scope was initially unable to pass through the stricture in 135(58%) procedures, and after dilation was able to pass through in 185(80%). The dilation was considered endoscopically successful in 216 (93%) procedures. There were 6 complications with 3 perforations, abdominal pain in 2 and bleeding in 1 patient. Definitive surgery was needed for the stricture in 21 patients. Conclusions: Endoscopic dilation of strictures in Crohn's disease is safe and effective, with a majority of procedures accomplished with conscious sedation. It should be considered for management of these strictures before surgical resection.
Cumulative Probability of Recurrence of HS
Mo1245 Impact of Inflammatory Bowel Disease Activity on the Incidence of NonAlcoholic Fatty Liver Disease: A 7-Year Longitudinal Study Ngoc Han Quang Le, Kathleen C. Rollet, Waqqas Afif, Alain Bitton, Talat Bessissow, Giada Sebastiani Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease in Western countries. It is classically associated with metabolic risk factors. Conflicting data exist on its frequency and associated risk factors in patients with inflammatory bowel disease (IBD). Methods: This was a retrospective, longitudinal study of IBD patients without known liver disease evaluated at least twice during 2006-2013 in a tertiary care centre. Clinical markers for IBD activity were collected at a 6 month-visit interval. Patients were divided into 2 groups: active IBD group and clinical remission group. NAFLD was defined as a Hepatic Steatosis Index (HSI) ≥ 36 or as positive imaging (ultrasound or CT scan). During a median follow-up of 43.2 months (Q1, 16.8; Q3, 72) we evaluated longitudinally the incidence of NAFLD and associated risk factors. Cox regression analysis was used to identify risk factors for the development of NAFLD. Results: 232 patients (median age 33.8, 50% males) were included. Most patients (68%) had Crohn's disease, the majority of whom (41%) had ileocolonic disease. 27.9% of patients had at least one metabolic comorbidity. The overall prevalence of NAFLD in our cohort was 41%. Thirty-five patients already had the outcome at baseline and were excluded from the longitudinal analysis. The distribution of the study groups among the remaining 197 was as follows: 59% had active IBD, 41% were in clinical remission. Sixty (31%) patients developed NAFLD during the longitudinal analysis, 60% of whom were in the active IBD group. This translated to an overall rate of progression to NAFLD of 8.2 per 100 patient-years (PY). The active IBD group had a higher rate of progression when compared to the clinical remission group (9 vs. 7.3 per 100 PY). Metabolic comorbidities did not correlate with NAFLD in our cohort of IBD patients. Instead, patients who developed NAFLD were older (40.2 vs. 31.9 years), were diagnosed with IBD at an older age (29 vs. 23.2 years) and had a longer duration of disease (9.3 vs. 5.9 years) at baseline. Active IBD, which was time-updated at each visit (HR: 1.87, 95% CI: 1.133.11), and age at IBD diagnosis (HR: 1.1, 95% CI: 1.03-1.17) were independent contributors to NAFLD. Conclusion: NAFLD is an unexpectedly frequent condition in patients with IBD. Disease activity is the major risk factor for the development of NAFLD in this setting. This may represent one more incentive to achieve and maintain early clinical remission in those patients.
AGA Abstracts
Mo1247 Autoimmune Pancreatitis is Associated With Aggressive IBD Alyssa M. Parian, Elham Afghani, Berkeley N. Limketkai, Animesh Jain, Christina Y. Ha, Vikesh K. Singh, Mark Lazarev Objectives: The association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has previously been described, although there is a paucity of data on the natural history and severity of combined AIP and IBD. Our objectives were to determine the prevalence of IBD in AIP patients at a tertiary referral hospital and to describe the progression and severity of the disease courses. Methods: A complete database of AIP patients who met international consensus disease criteria from 2000 to 2012 was queried for the presence of IBD, including Crohn's disease (CD), ulcerative colitis (UC) and IBD - undetermined (IBDU). Patient demographics, timing and methods of diagnosis and treatment courses for patients with IBD + AIP were tabulated. Descriptive statistics were used. Results: Seven of 75 total AIP patients (9.3%) had a diagnosis of IBD, 6 with UC and 1 with CD. Four patients were diagnosed with IBD within a year after the AIP diagnosis, and 3 had IBD prior to the AIP diagnosis. Only 2 patients had pancreas pathology, both confirmed as AIP type 1. The other 5 patients had probable type 2 AIP based on demographic and clinical features. The 5 patients (71%) with probable AIP 2 were younger at AIP presentation (age range 2038) than the 2 patients (29%) with AIP 1 (ages 71 and 72). Only 2 of the 6 patients (33%) that had serum IgG4 levels drawn were elevated. All 3 of the patients that had colonic biopsies stained for IgG4 were positive (>10 / hpf). All patients, except one who had a Whipple procedure, underwent a 12 week oral steroid taper for the AIP. One patient (#4) did not achieve AIP remission and required a second steroid taper. In addition, he had refractory UC with minimal response to steroids, and no response to thiopurines and antiTNF agents. Overall, 5 patients (71%) had severe IBD characterized by either the need for surgery or biologic therapy. Conclusion: IBD associated with AIP may have a more aggressive phenotype with 71% of patients requiring either surgery or biologic therapy. Further studies and longer follow up are needed to better understand the colitis associated with AIP and accordingly establish more effective treatment regimens.
S-596
Mo1249
INTRODUCTION: Muscle wasting or sarcopenia arising from chronic inflammation can be found in 60% of Crohn's disease (CD) patients1. The transcriptional protein NF-Kb reduces muscle formation through MyoD transcription2 and increases muscle breakdown by proteolysis3. As TNF is a potent activator of NF-Kb, and the anti-TNF agents infliximab (IFX) prevents NF-Kb activation, we assessed CD subjects treated with IFX for gains in muscle volume and strength. METHODS: We conducted a prospective, cohort study in CD subjects aged 18-70 presenting with an acute disease flare (Crohn's Disease Activity Index {CDAI} >220 and elevated C-reactive protein {CRP}). Subjects were instructed not to vary diet or activity and concomitant medications were kept stable. At week 0 (pretreatment), week 12 and week 21 of IFX induction regimen, we assessed (1) MRI volume of the quadriceps femoris at the anatomical mid-thigh; (2) maximal concentric quadriceps contractions strength in each leg at three specific speeds of contraction; (3) physical activity by validated instrument (IPAQ); (4) Three-day food record of intake and composition (food-weighing method); (5) Serum levels of cytokines TNFa, and IL6. RESULTS: 19 subjects (58% female, mean age 33.2 + 10.7 y) were recruited based on preliminary power calculations. Mean baseline CDAI was 358 + 79 and body mass index was 24 + 4.8. IFX therapy led to significant progressive gains in muscle volume and muscle strength (Table). Muscle volume gain correlated with male gender. Significant gains in muscle strength were noted at each speed of contraction in both legs and were unrelated to age or gender. There were no significant differences in physical activity level throughout the study period, nor significant differences in calorie, protein and total fat intake. Serum TNFa fell significantly from pretreatment levels, as expected. CONCLUSION: We demonstrate for the first time that the anti-TNF agent IFX reverses inflammatory sarcopenia. Besides direct anti-inflammatory properties, IFX may have muscle protective effects, and may reduce time to return to work and improve quality of life. References:(1) Schneider et al. Inflamm Bowel Dis 2008; 14: 1562 - 8. (2) Guttridge et al. Science 2000; 289 (5488): 2363-6. (3) Cai et al. Cell 2004; 119 (2): 285-98.
AIP = autoimmune pancreatitis; maj pap = major papilla Mo1248 Rates and Predictors of Endoscopic and Clinical Recurrence After Primary Ileocolic Resection for Crohn's Disease Kyle J. Fortinsky, David Kevans, Judy Qiang, Wei Xu, Gordon R. Greenberg, A. Hillary Steinhart, Zane Cohen, Helen M. MacRae, Felipe Bellolio, Joanne M. Stempak, Robin S. McLeod, Mark S. Silverberg Background: Most patients with Crohn's disease (CD) will undergo at least one intestinal resection during the course of their disease. Postoperative endoscopic recurrence is reported to occur in 60-80% of patients within 1 year. The utility of postoperative medical prophylaxis and the treatment of mild endoscopic recurrence continue to be debated in the literature. Aims: To document rates and predictors of endoscopic and clinical recurrence after primary ileocolic resection for CD in a large, tertiary academic center. Methods: We performed a retrospective chart review on patients who underwent primary ileocolic resection for CD between 1991 and 2010 at our institution. Only patients with clinical follow-up including postoperative endoscopic assessment at our institution were included in our analysis. Details of preoperative disease behavior, medication history, surgical pathology, and postoperative endoscopic, radiologic, and clinical course were recorded. Endoscopic recurrence (ER) was defined using the Rutgeerts score (RS) where RS ≥ 1 indicated ER. Clinical recurrence (CR) was defined as symptoms of CD with endoscopic or radiologic evidence of neo-terminal ileal disease. Results: 171 patients met inclusion criteria (median age at diagnosis 22 years, 50% male; 19% current smokers). 66 patients (39%) received postoperative medical prophylaxis. The cumulative probability of ER (RS ≥ 1) at 1, 2 and 5 years was: 29%, 51% and 77%, respectively. In a multivariate model, the only independent predictors of ER were the absence of postoperative medical prophylaxis (HR 1.5; 95% CI, 1.1-2.2; P = 0.03) and penetrating disease behavior (HR 1.5; 95% CI, 1.0-2.1; P = 0.05). In patients not receiving postoperative medical prophylaxis, perianal disease was associated with ER (HR 1.7; P = 0.05). The cumulative probability of CR at 1, 2 and 5 years was: 8%, 13% and 27%, respectively. In a multivariate model, the only independent predictors of CR were perioperative smoking (HR 2.3; 95% CI, 1.3-4.0; P < 0.01) and preoperative upper gastrointestinal tract involvement (HR 4.0; 95% CI, 1.8-8.3; P < 0.001). There was a higher rate of clinical recurrence in patients with RS-2 compared to RS-1 on endoscopy (HR 2.5; 95% CI, 1.25.9; P = .02). Conclusions: Rates of early ER in this cohort are less than previously reported in the literature. Postoperative medical prophylaxis did decrease the likelihood of ER while certain phenotypes of CD appear to increase the risk of developing ER and CR. The majority of patients with ER did not develop CR, which may reflect the increasing use of postoperative endoscopic surveillance that can facilitate early treatment of ER prior to the evolution of clinical symptoms.
Mo1250 Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) Specific ELISPOT Assays Detect Frequent Reactivation of CMV and EBV in Inflammatory Bowel Disease Dominik Bettenworth, Ross Matthias, Markus Brückner, Joria B. Martin, Frank Lenze, Hauke Heinzow, Andreas Lügering, Tobias M. Nowacki Objective: Patients suffering from inflammatory bowel disease (IBD) are often immunosuppressed rendering these patients susceptible to the reactivation of latent viral infections such as CMV or EBV. However, reliable non-invasive tools to detect viral reactivation are missing, especially since reactivation mainly occurs in the gut mucosa and not necessarily results in viremia. We hypothesized that the detection of CMV- and EBV-specific CD8 effector T cells should allow the distinction between dormant and reactivated viral infection. Methods: Peripheral blood was obtained from 26 IBD patients (16 Ulcerative Colitis UC, 10 Crohns Disease CD) and age-matched female and male healthy human donors after informed consent. Disease parameters were recorded and Colitis or Crohns disease activity indices determined. Peripheral blood mononuclear cells (PBMC) were isolated and single cell resolution ex vivo ELISPOT measurements of CMV- and EBV-antigen triggered release of Interferon-γ (IFNγ), Granzyme B (GzB) and Perforin (PFN) were employed to identify actively ongoing T cell responses towards these viruses. Detection of effector T cells, delineated by GzB and PFN production, determined antiviral activity and was correlated with disease activity indices and immunohistochemistry staining of tissue samples where available. Results: CMV- and EBV-specific T cells were found to be in an activated state in a significant number of IBD patients; in particular during flares of disease (EBV reactivity was detected in 6 of 16 UC and 5 of 10 CD patients, CMV reactivity in 6 of 16 UC and 3 of 10 CD patients). No reactivity was found in healthy controls (p<0.01). While CMV reactivity was associated with greater disease activity with significantly less CMV reactive patients being in clinical remission (p<0.05), EBV reactivity was not associated with active disease (remission rates 33% vs. 43% for EBV reactive/nonreactive, respectively). Additionally, reactivity against CMV was associated with longer disease duration in CD (p<0.01) but not in UC (ns) while EBV reactivity was not associated with disease duration. Interestingly, PCR analysis on serum or immunohistochemistry staining of tissue samples frequently failed to detect CMV during flares. A correlation between the CMV immune response and current treatment with azathioprine was not observed. Conclusion: Our data support the importance of CMV and EBV infection in IBD. Single cell resolution ex vivo ELISPOT measurements of IFN-γ, GzB and PFN are a reasonable non-invasive tool to detect viral reactivation in IBD that might contribute to the intestinal inflammation. Immunological monitoring of viral reactivation might provide rational patient-tailored therapeutic options of immunosuppressive and/or antiviral treatment to ameliorate the course of disease.
Survival free of endoscopic recurrence after primary ileocolic resection for Crohn's disease.
S-597
AGA Abstracts
AGA Abstracts
The Anti-TNF Agent Infliximab Reverses Inflammatory Sarcopenia in Crohn's Disease Kavitha Subramaniam, Kieran Fallon, Thomas Ruut, Ross Mckay, Bruce Shadbolt, Sophia Ang, Matthew Cook, Jan Platten, Paul Pavli, Doug Taupin
infections (OR 1.16, p=0.023), and shock (OR 1.30, p=0.022). Obese IBD patients were also more likely to have pulmonary complications (OR 1.21, p=0.021). There was no difference in cardiovascular complications (OR 1.09, p=0.524), perforations (OR 1.04, p= 0.707), venous thromboembolism (OR 1.18, p=0.399), or death (OR 0.73, p=0.067) when comparing obese with non-obese IBD surgeries. Obese IBD hospitalizations had marginally shorter lengths of stay by 0.61 days (p=0.005), but the daily cost was higher by $1324 (p<0.001) compared with non-obese IBD hospitalizations. CONCLUSIONS: In this nationwide analysis, obese IBD patients had increased rates of several post-operative complications. Although the lengths of stay were similar, the daily cost of hospitalizations was higher among obese IBD patients.
Mo1246 Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Study Siddhant Yadav, Jithinraj Edakkanambeth Varayil, Natasha Kamal, William S. Harmsen, David A. Wetter, Mark Denis P. Davis, William J. Tremaine, Jean-Frederic Colombel, Edward V. Loftus Background and Aims: An association between hidradenitis suppurativa (HS) and inflammatory bowel disease (IBD) has been described, but the relation between the two diseases is not very well understood or documented. We sought to better quantify the relationship, if one is present, between these two conditions. Methods: A well-established population-based inception cohort of North American IBD patients diagnosed between 1970 and 2004 were followed through death, loss of follow-up or to December 31, 2011 for the diagnosis of HS. We documented the extent and severity of IBD, and the putative risk factors for HS such as smoking, obesity, skin cancers and depression. The Hurley stage I, II, or III, (limited to extensive) was noted as well as the area of involvement, treatment and recurrence. The cumulative incidence of HS after IBD diagnosis was estimated using the Kaplan-Meier method. Results: Our 1970-2004 cohort of IBD patients included a total of 678 patients. Median follow-up was 19.8 years (range, 0.15 - 43.4). Ten patients were diagnosed with HS. Of these, 9 were diagnosed after the occurrence of IBD. The cumulative probability of HS after IBD diagnosis is shown in Table 1. Eight were females; 4 patients had ulcerative colitis and 6 had Crohn's disease. In patients with Crohn's disease, all had internal fistulas. Eight patients were smokers, 3 had skin cancer, and 6 were obese and had depression. Five patients had other dermatoses such as actinic keratosis. One patient each had acne, pilonidal disease, internal malignancy and pyoderma gangrenosum. There was no family history of HS. Seven patients had a Hurley staging of II. Six patients each had lesions involving the axilla and groin, while 2 had chest involvement. Six patients were treated with antibiotics, 3 with corticosteroids, and 5 underwent surgery. There was recurrence of HS in 4 patients. The cumulative probability of recurrence of HS is listed in Table 2. Conclusion: HS is a rare but important complication of IBD, with up to 2 - 3% of patients developing HS over 30 years from diagnosis. Most patients with HS and IBD were females. Patients with UC and CD have a similar risk for HS. Recurrent disease after surgical excision is common. Cumulative Probability of HS after IBD diagnosis
Mo1244 Outcomes of Endoscopic Therapy of Luminal Strictures in Crohn's Disease Jithinraj Edakkanambeth Varayil, Edward V. Loftus, Nayantara Coelho Prabhu Background: There is limited data on efficacy of endoscopic management of strictures in Crohn's disease. At our tertiary referral center which has a large inflammatory bowel disease practice, we sought to describe the long term efficacy of endoscopic dilation of luminal strictures. Methods: We identified all patients with endoscopic dilation of Crohn's strictures between 1/1/1990 and 11/30/2013. We performed an IRB-approved retrospective review of a random sampling of 100 of these patients. Demographics, disease characteristics including medication use, endoscopic procedural details, and long term outcome including need for surgery were analyzed. Endoscopic success was defined as effacement of dilating balloon or ability to pass the scope through the stricture after dilation. Results: A total of 231 endoscopic stricture dilations were performed in 100 patients. The mean age was 52+14 years; 51% were male. The median follow-up duration was 5.1 (IQR 2.1-9.8) years. The median duration of Crohn's disease before the first dilation was 23 (IQR 12-33) years. 35% had ileal involvement, 28% ileo-colonic, and 25% colonic; 78% had had prior intestinal resections. The commonest medications at the time of dilation were anti-TNF agents (30%), Azathioprine (30%), or 5-ASAs (22%). Sigmoidoscopy or colonoscopy 199 (86%) was the commonest procedure. The commonest stricture locations were ileo-colonic anastomosis, colon, and ano-rectal junction in 98 (42%), 42 (18%), and 38 (16%) procedures, respectively. Fifty (22%) procedures had preceding radiographic imaging with CT enterography (56%) being the commonest type and patients were symptomatic at 204 (88%) procedures. 60 patients had only 1 endoscopic dilation, 16 patients had 2, 8 patients had 3, and 16 had more than 3 procedures. Conscious sedation was used in 195 (84%) procedures. The median initial diameter of the stricture was 9 (IQR 7-10)mm, and inflammation was seen at the stricture site in 86 (37%) procedures. Dilation was performed using a balloon in 192 (83%) procedures, with a median maximal balloon size of 15(IQR 14-18) mm; using Hegar or Savary dilators in 29 (13%) procedures, with a median maximal size of 16 (IQR 12-18)mm. The scope was initially unable to pass through the stricture in 135(58%) procedures, and after dilation was able to pass through in 185(80%). The dilation was considered endoscopically successful in 216 (93%) procedures. There were 6 complications with 3 perforations, abdominal pain in 2 and bleeding in 1 patient. Definitive surgery was needed for the stricture in 21 patients. Conclusions: Endoscopic dilation of strictures in Crohn's disease is safe and effective, with a majority of procedures accomplished with conscious sedation. It should be considered for management of these strictures before surgical resection.
Cumulative Probability of Recurrence of HS
Mo1245 Impact of Inflammatory Bowel Disease Activity on the Incidence of NonAlcoholic Fatty Liver Disease: A 7-Year Longitudinal Study Ngoc Han Quang Le, Kathleen C. Rollet, Waqqas Afif, Alain Bitton, Talat Bessissow, Giada Sebastiani Background: Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease in Western countries. It is classically associated with metabolic risk factors. Conflicting data exist on its frequency and associated risk factors in patients with inflammatory bowel disease (IBD). Methods: This was a retrospective, longitudinal study of IBD patients without known liver disease evaluated at least twice during 2006-2013 in a tertiary care centre. Clinical markers for IBD activity were collected at a 6 month-visit interval. Patients were divided into 2 groups: active IBD group and clinical remission group. NAFLD was defined as a Hepatic Steatosis Index (HSI) ≥ 36 or as positive imaging (ultrasound or CT scan). During a median follow-up of 43.2 months (Q1, 16.8; Q3, 72) we evaluated longitudinally the incidence of NAFLD and associated risk factors. Cox regression analysis was used to identify risk factors for the development of NAFLD. Results: 232 patients (median age 33.8, 50% males) were included. Most patients (68%) had Crohn's disease, the majority of whom (41%) had ileocolonic disease. 27.9% of patients had at least one metabolic comorbidity. The overall prevalence of NAFLD in our cohort was 41%. Thirty-five patients already had the outcome at baseline and were excluded from the longitudinal analysis. The distribution of the study groups among the remaining 197 was as follows: 59% had active IBD, 41% were in clinical remission. Sixty (31%) patients developed NAFLD during the longitudinal analysis, 60% of whom were in the active IBD group. This translated to an overall rate of progression to NAFLD of 8.2 per 100 patient-years (PY). The active IBD group had a higher rate of progression when compared to the clinical remission group (9 vs. 7.3 per 100 PY). Metabolic comorbidities did not correlate with NAFLD in our cohort of IBD patients. Instead, patients who developed NAFLD were older (40.2 vs. 31.9 years), were diagnosed with IBD at an older age (29 vs. 23.2 years) and had a longer duration of disease (9.3 vs. 5.9 years) at baseline. Active IBD, which was time-updated at each visit (HR: 1.87, 95% CI: 1.133.11), and age at IBD diagnosis (HR: 1.1, 95% CI: 1.03-1.17) were independent contributors to NAFLD. Conclusion: NAFLD is an unexpectedly frequent condition in patients with IBD. Disease activity is the major risk factor for the development of NAFLD in this setting. This may represent one more incentive to achieve and maintain early clinical remission in those patients.
AGA Abstracts
Mo1247 Autoimmune Pancreatitis is Associated With Aggressive IBD Alyssa M. Parian, Elham Afghani, Berkeley N. Limketkai, Animesh Jain, Christina Y. Ha, Vikesh K. Singh, Mark Lazarev Objectives: The association between autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) has previously been described, although there is a paucity of data on the natural history and severity of combined AIP and IBD. Our objectives were to determine the prevalence of IBD in AIP patients at a tertiary referral hospital and to describe the progression and severity of the disease courses. Methods: A complete database of AIP patients who met international consensus disease criteria from 2000 to 2012 was queried for the presence of IBD, including Crohn's disease (CD), ulcerative colitis (UC) and IBD - undetermined (IBDU). Patient demographics, timing and methods of diagnosis and treatment courses for patients with IBD + AIP were tabulated. Descriptive statistics were used. Results: Seven of 75 total AIP patients (9.3%) had a diagnosis of IBD, 6 with UC and 1 with CD. Four patients were diagnosed with IBD within a year after the AIP diagnosis, and 3 had IBD prior to the AIP diagnosis. Only 2 patients had pancreas pathology, both confirmed as AIP type 1. The other 5 patients had probable type 2 AIP based on demographic and clinical features. The 5 patients (71%) with probable AIP 2 were younger at AIP presentation (age range 2038) than the 2 patients (29%) with AIP 1 (ages 71 and 72). Only 2 of the 6 patients (33%) that had serum IgG4 levels drawn were elevated. All 3 of the patients that had colonic biopsies stained for IgG4 were positive (>10 / hpf). All patients, except one who had a Whipple procedure, underwent a 12 week oral steroid taper for the AIP. One patient (#4) did not achieve AIP remission and required a second steroid taper. In addition, he had refractory UC with minimal response to steroids, and no response to thiopurines and antiTNF agents. Overall, 5 patients (71%) had severe IBD characterized by either the need for surgery or biologic therapy. Conclusion: IBD associated with AIP may have a more aggressive phenotype with 71% of patients requiring either surgery or biologic therapy. Further studies and longer follow up are needed to better understand the colitis associated with AIP and accordingly establish more effective treatment regimens.
S-596
Mo1249
INTRODUCTION: Muscle wasting or sarcopenia arising from chronic inflammation can be found in 60% of Crohn's disease (CD) patients1. The transcriptional protein NF-Kb reduces muscle formation through MyoD transcription2 and increases muscle breakdown by proteolysis3. As TNF is a potent activator of NF-Kb, and the anti-TNF agents infliximab (IFX) prevents NF-Kb activation, we assessed CD subjects treated with IFX for gains in muscle volume and strength. METHODS: We conducted a prospective, cohort study in CD subjects aged 18-70 presenting with an acute disease flare (Crohn's Disease Activity Index {CDAI} >220 and elevated C-reactive protein {CRP}). Subjects were instructed not to vary diet or activity and concomitant medications were kept stable. At week 0 (pretreatment), week 12 and week 21 of IFX induction regimen, we assessed (1) MRI volume of the quadriceps femoris at the anatomical mid-thigh; (2) maximal concentric quadriceps contractions strength in each leg at three specific speeds of contraction; (3) physical activity by validated instrument (IPAQ); (4) Three-day food record of intake and composition (food-weighing method); (5) Serum levels of cytokines TNFa, and IL6. RESULTS: 19 subjects (58% female, mean age 33.2 + 10.7 y) were recruited based on preliminary power calculations. Mean baseline CDAI was 358 + 79 and body mass index was 24 + 4.8. IFX therapy led to significant progressive gains in muscle volume and muscle strength (Table). Muscle volume gain correlated with male gender. Significant gains in muscle strength were noted at each speed of contraction in both legs and were unrelated to age or gender. There were no significant differences in physical activity level throughout the study period, nor significant differences in calorie, protein and total fat intake. Serum TNFa fell significantly from pretreatment levels, as expected. CONCLUSION: We demonstrate for the first time that the anti-TNF agent IFX reverses inflammatory sarcopenia. Besides direct anti-inflammatory properties, IFX may have muscle protective effects, and may reduce time to return to work and improve quality of life. References:(1) Schneider et al. Inflamm Bowel Dis 2008; 14: 1562 - 8. (2) Guttridge et al. Science 2000; 289 (5488): 2363-6. (3) Cai et al. Cell 2004; 119 (2): 285-98.
AIP = autoimmune pancreatitis; maj pap = major papilla Mo1248 Rates and Predictors of Endoscopic and Clinical Recurrence After Primary Ileocolic Resection for Crohn's Disease Kyle J. Fortinsky, David Kevans, Judy Qiang, Wei Xu, Gordon R. Greenberg, A. Hillary Steinhart, Zane Cohen, Helen M. MacRae, Felipe Bellolio, Joanne M. Stempak, Robin S. McLeod, Mark S. Silverberg Background: Most patients with Crohn's disease (CD) will undergo at least one intestinal resection during the course of their disease. Postoperative endoscopic recurrence is reported to occur in 60-80% of patients within 1 year. The utility of postoperative medical prophylaxis and the treatment of mild endoscopic recurrence continue to be debated in the literature. Aims: To document rates and predictors of endoscopic and clinical recurrence after primary ileocolic resection for CD in a large, tertiary academic center. Methods: We performed a retrospective chart review on patients who underwent primary ileocolic resection for CD between 1991 and 2010 at our institution. Only patients with clinical follow-up including postoperative endoscopic assessment at our institution were included in our analysis. Details of preoperative disease behavior, medication history, surgical pathology, and postoperative endoscopic, radiologic, and clinical course were recorded. Endoscopic recurrence (ER) was defined using the Rutgeerts score (RS) where RS ≥ 1 indicated ER. Clinical recurrence (CR) was defined as symptoms of CD with endoscopic or radiologic evidence of neo-terminal ileal disease. Results: 171 patients met inclusion criteria (median age at diagnosis 22 years, 50% male; 19% current smokers). 66 patients (39%) received postoperative medical prophylaxis. The cumulative probability of ER (RS ≥ 1) at 1, 2 and 5 years was: 29%, 51% and 77%, respectively. In a multivariate model, the only independent predictors of ER were the absence of postoperative medical prophylaxis (HR 1.5; 95% CI, 1.1-2.2; P = 0.03) and penetrating disease behavior (HR 1.5; 95% CI, 1.0-2.1; P = 0.05). In patients not receiving postoperative medical prophylaxis, perianal disease was associated with ER (HR 1.7; P = 0.05). The cumulative probability of CR at 1, 2 and 5 years was: 8%, 13% and 27%, respectively. In a multivariate model, the only independent predictors of CR were perioperative smoking (HR 2.3; 95% CI, 1.3-4.0; P < 0.01) and preoperative upper gastrointestinal tract involvement (HR 4.0; 95% CI, 1.8-8.3; P < 0.001). There was a higher rate of clinical recurrence in patients with RS-2 compared to RS-1 on endoscopy (HR 2.5; 95% CI, 1.25.9; P = .02). Conclusions: Rates of early ER in this cohort are less than previously reported in the literature. Postoperative medical prophylaxis did decrease the likelihood of ER while certain phenotypes of CD appear to increase the risk of developing ER and CR. The majority of patients with ER did not develop CR, which may reflect the increasing use of postoperative endoscopic surveillance that can facilitate early treatment of ER prior to the evolution of clinical symptoms.
Mo1250 Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) Specific ELISPOT Assays Detect Frequent Reactivation of CMV and EBV in Inflammatory Bowel Disease Dominik Bettenworth, Ross Matthias, Markus Brückner, Joria B. Martin, Frank Lenze, Hauke Heinzow, Andreas Lügering, Tobias M. Nowacki Objective: Patients suffering from inflammatory bowel disease (IBD) are often immunosuppressed rendering these patients susceptible to the reactivation of latent viral infections such as CMV or EBV. However, reliable non-invasive tools to detect viral reactivation are missing, especially since reactivation mainly occurs in the gut mucosa and not necessarily results in viremia. We hypothesized that the detection of CMV- and EBV-specific CD8 effector T cells should allow the distinction between dormant and reactivated viral infection. Methods: Peripheral blood was obtained from 26 IBD patients (16 Ulcerative Colitis UC, 10 Crohns Disease CD) and age-matched female and male healthy human donors after informed consent. Disease parameters were recorded and Colitis or Crohns disease activity indices determined. Peripheral blood mononuclear cells (PBMC) were isolated and single cell resolution ex vivo ELISPOT measurements of CMV- and EBV-antigen triggered release of Interferon-γ (IFNγ), Granzyme B (GzB) and Perforin (PFN) were employed to identify actively ongoing T cell responses towards these viruses. Detection of effector T cells, delineated by GzB and PFN production, determined antiviral activity and was correlated with disease activity indices and immunohistochemistry staining of tissue samples where available. Results: CMV- and EBV-specific T cells were found to be in an activated state in a significant number of IBD patients; in particular during flares of disease (EBV reactivity was detected in 6 of 16 UC and 5 of 10 CD patients, CMV reactivity in 6 of 16 UC and 3 of 10 CD patients). No reactivity was found in healthy controls (p<0.01). While CMV reactivity was associated with greater disease activity with significantly less CMV reactive patients being in clinical remission (p<0.05), EBV reactivity was not associated with active disease (remission rates 33% vs. 43% for EBV reactive/nonreactive, respectively). Additionally, reactivity against CMV was associated with longer disease duration in CD (p<0.01) but not in UC (ns) while EBV reactivity was not associated with disease duration. Interestingly, PCR analysis on serum or immunohistochemistry staining of tissue samples frequently failed to detect CMV during flares. A correlation between the CMV immune response and current treatment with azathioprine was not observed. Conclusion: Our data support the importance of CMV and EBV infection in IBD. Single cell resolution ex vivo ELISPOT measurements of IFN-γ, GzB and PFN are a reasonable non-invasive tool to detect viral reactivation in IBD that might contribute to the intestinal inflammation. Immunological monitoring of viral reactivation might provide rational patient-tailored therapeutic options of immunosuppressive and/or antiviral treatment to ameliorate the course of disease.
Survival free of endoscopic recurrence after primary ileocolic resection for Crohn's disease.
S-597
AGA Abstracts
AGA Abstracts
The Anti-TNF Agent Infliximab Reverses Inflammatory Sarcopenia in Crohn's Disease Kavitha Subramaniam, Kieran Fallon, Thomas Ruut, Ross Mckay, Bruce Shadbolt, Sophia Ang, Matthew Cook, Jan Platten, Paul Pavli, Doug Taupin