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Mo1721 Mesenchymal Stem Cells Regulates the Development of Cholangitis Associated With Chronic Colitis
Table 2. Absolute absenteeism (hours/28 days), mean days missed by reason in 28 days for working CD patients, UC patients, and healthy controls
Mo1721 Mesenchymal Stem Cells Regulates the Development of Cholangitis Associated With Chronic Colitis Hui Li, Guochao Niu, Lei Liu, Hong Zhang, Hui Wu, Jinbo Guo, Jia Song, Xiaolan Zhang, David Q. Shih Background: A Hepatobiliary manifestation, cholangitis, is frequently encountered in inflammatory bowel disease (IBD). The mesenchymal stem cells (MSCs), having the ability of selfrenewal and the multiplex differentiation, are multipotent stem cells, which may have therapeutic effect on the cholangitis associated with IBD. Aim: To investigate the therapeutic effect of MSCs on cholangitis associated with DSS-induced chronic colitis. Methods: Mice were grouped as follows: DSS group (received 2%DSS drinking water, n=10), MSCs group (received 2%DSS drinking water and MSCs, n=10) and Control group (received PBS, n= 10). The disease activity index (DAI), the change of body weight, colon length and damage store of the colon were observed. The histopathology changes of liver were determined correspondingly. The expressions of TNF-α protein and IFN-γ protein both in colon mucosa and in liver were measured by Immunohistochemisty. The test of liver function was measured by biochemical method. Results: The results of body weight, DAI, colon length and histological assessment of colon and liver revealed that in the model group, the more severe colitis the mice showed, the more severe inflammatory cell infiltrate into the bile duct, which was alleviated after the treatment of MSCs (P<0.05). The serum level of total protein (TP) and albumin (ALB) in the model group were decreased compared with that of the control group, after treatment they significantly increased (P<0.05). The protein expressions of TNF-α and IFN-γ both in colon mucosa and in hepatic portal area up-regulated in the model group (P<0.05), and down-regulated in the treatment group compared with that in the control group (P<0.05). Conclusions: The data show that the activity of cholangitis is consistent with that of chronic colitis. MSCs may be a novel therapeutic drug for the treatment of cholangitis associated with chronic colitis.
Mo1719 Retesting for Latent Tuberculosis in Patients With Inflammatory Bowel Disease After Exposure to Biologics Pavol Papay, Christian Primas, Alexander Eser, Gottfried Novacek, Stefan Winkler, Sophie Frantal, Sieglinde Angelberger, Andrea Mikulits, Clemens Dejaco, Harald Vogelsang, Walter Reinisch BACKGROUND/AIM: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring for TB reactivation and/or infection in this risk group are lacking. METHODS: We retested consecutive patients with inflammatory bowel disease (IBD) under therapy with TNFi for a minimum of 5 months for LTB by interferon-γ release assay (IGRA) and tuberculin skin test (TST). From each subject a detailed patient history and concomitant therapy were captured. RESULTS: After a median of 34.9 weeks (20.7-177.7) IGRA was retested in 184/227 patients (81.1%; Crohn's disease n= 139, ulcerative colitis n=45) initially screened for LTB and subsequently treated with TNFi. Additionally TST was re-administered in 144/227 subjects (63.4%). The majority of patients was TNFi naïve (147/227, 79.9%). In 32 subjects isoniazid was provided prior and concurrently to TNFi due to LTB. In this subgroup retesting for LTB resulted in a reversion to negative in 6/13 patients (46.2%) and in 3/24 patients (12.5%, P=0.08) with a positive IGRA and positive TST at baseline, respectively. In patients without LTB at baseline no permanent IGRA conversion, but 6/144 (4.2%) TST conversions from negative to positive were observed. No single case of TB reactivation or infection was observed during the observation period. CONCLUSION: A conversion of IGRA during treatment with TNFi was not observed, but occurred for TST. IGRA frequently reverts to negative in patients with LTB after specific therapy and seems to be a sensitive method to monitor patients for LTB under treatment with TNFi.
Mo1722 High Body Mass Index and Asthma are Risk Factors Associated With Peristomal Pyoderma Gangrenosum Xianrui Wu, Saurabh Mukewar, Bo Shen Background: As an unusual variant of pyoderma gangrenosum, peristomal pyoderma gangrenosum (PPG) has been reported in small sample-sized studies. However, clinical features and risk factors for PPG are not well defined, and misdiagnosis is frequent. Aim: To compare stoma patients with or without PPG to identify clinical features as well as risk factors associated with development of PPG. Methods: We conducted an IRB-approved case-control study. Patients with a diagnosis of PPG were enrolled as cases, and the control group consisted of patients who had stoma construction but without pyoderma gangrenosum. Cases were obtained through searching the database of Cleveland Clinic using the “ICD 9” code from January 2008 to May 2011. The control group was selected by strictly matching on underlying diseases and type of stoma with a ratio of 3:1. Patients with pyoderma gangrenosum at other sites rather than peristomal area were excluded. Results: Eleven PPG patients were enrolled as cases (2 male and 9 female), all of them were biopsied for the purpose of exclusion. Mean age at the diagnosis of PPG was 41.9±14.0 years. Underlying disease was Crohn's disease (CD) for 6 patients, and ulcerative colitis (UC) for 5. Nine patients had end ileostomy, 1 had loop ileostomy, and 1 had colostomy. The time interval from the stoma construction to the diagnosis of PPG ranged from 14 days to 19.7 years. Two patients had a history of pyoderma gangrenosum at lower extremity, and the other two patients initially presented with PPG, but lower extremity got involved later. The largest diameter of PPG in this cohort was 15 cm. Eight patients had at least 1 relapse of PPG after initial healing, and a parallel course with PPG occurred in 2 patients. All 11 patients were locally injected with steroids, 8 of them needed systemic steroids, 6 needed immunosuppressive agents, and 4 patients need infliximab or adalimumab. After a median follow-up of 10.2 (range: 2.9-133.1) months, PPG healed in 7 patients and improved in 4 patients. Compared with control group, PPG patients were found to have higher body mass index (BMI), shorter duration of inflammatory bowel disease (IBD) and more concurrent asthma. However, no difference was found between the two groups in terms of age, gender, social status, extraintestinal manifestations, comorbidities, family history of IBD, history of stoma construction, preoperative drug use, duration of stoma, and stoma complication (p>0.05, Table). Conclusion: PPG can develop at any time after stoma construction in patients with underlying IBD,
Proportion of patients with IGRA / TST reversion with baseline positive IGRA or TST under isoniazid therapy Mo1720 Frequency and Chronology of Extraintestinal Manifestations in the Swiss Inflammatory Bowel Disease Cohort Stephan R. Vavricka, Claudine Gantenbein, Muriel Spoerri, Bettina M. Prinz Vavricka, Ekaterina Safroneeva, Alexander Navarini, Alain Schoepfer Background: Data on the frequency of extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) is scarce, especially the one evaluating the time of occurrence of the EIM relative to IBD diagnosis. Aim: To assess the type and frequency of EIM in IBD patients and to evaluate when EIMs occur relative to IBD diagnosis. Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which collects data on a large
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AGA Abstracts
AGA Abstracts
sample of IBD patients from hospitals and private practices across Switzerland starting in 2005. While parametric data are shown as mean ± SD, non-parametric data are presented as median and interquartile range (IQR). Results: A total of 1143 patients were analyzed (572 (50%) female, mean age 42.1 ± 14.4 years): 629 (55%) with Crohn's disease (CD), 501 (44%) with ulcerative colitis (UC), and 13 (1%) with indeterminate colitis (IC). Of 1143 patients, 374 (32.7%) presented with EIM (65% with CD, 33% with UC, 2% with IC). Of those patients suffering from EIMs, 37.4% presented with one, 41.7% with two, 12.4% with three, 5.3% with four, and 3.2% with five EIM during their lifetime. The IBD patients initially presented with the following EIMs: peripheral arthritis (PA) 63.4%, ankylosing spondylitis (AS) 8.1%, primary sclerosing cholangitis (PSC) 6.0%, uveitis 5.7%, oral aphthosis 5.7%, erythema nodosum (EN) 5.0%, pyoderma gangrenosum 1.8%, psoriasis 0.7%. While 92.9% of EIM occurred once IBD diagnosis was established (median 72 months, IQR 9-147 months, p < 0.001), 7.1% of EIMs preceded IBD diagnosis (median time 28 months before IBD diagnosis, IQR 7-60 months). Over a course of a lifetime, IBD patients presented with the following EIM (total exceeds 100 due to potential presence of multiple EIM): peripheral arthritis 69.3%, oral aphthosis 23%, ankylosing spondylitis 19.4%, uveitis 15.5%, erythema nodosum 14.5%, PSC 7.8%, pyoderma gangrenosum 6%, psoriasis 2.8%. Conclusion: EIMs frequently occur in a lifetime of IBD patients. The vast majority of patients present with EIMs once IBD diagnosis has been established. IBD patients most often present with peripheral arthritis, ankylosing spondylitis and PSC as their first EIM. However, peripheral arthritis, oral aphthosis, and ankylosing spondylitis are the most common EIMs in a lifetime of IBD patients.
Mo1721 Mesenchymal Stem Cells Regulates the Development of Cholangitis Associated With Chronic Colitis Hui Li, Guochao Niu, Lei Liu, Hong Zhang, Hui Wu, Jinbo Guo, Jia Song, Xiaolan Zhang, David Q. Shih Background: A Hepatobiliary manifestation, cholangitis, is frequently encountered in inflammatory bowel disease (IBD). The mesenchymal stem cells (MSCs), having the ability of selfrenewal and the multiplex differentiation, are multipotent stem cells, which may have therapeutic effect on the cholangitis associated with IBD. Aim: To investigate the therapeutic effect of MSCs on cholangitis associated with DSS-induced chronic colitis. Methods: Mice were grouped as follows: DSS group (received 2%DSS drinking water, n=10), MSCs group (received 2%DSS drinking water and MSCs, n=10) and Control group (received PBS, n= 10). The disease activity index (DAI), the change of body weight, colon length and damage store of the colon were observed. The histopathology changes of liver were determined correspondingly. The expressions of TNF-α protein and IFN-γ protein both in colon mucosa and in liver were measured by Immunohistochemisty. The test of liver function was measured by biochemical method. Results: The results of body weight, DAI, colon length and histological assessment of colon and liver revealed that in the model group, the more severe colitis the mice showed, the more severe inflammatory cell infiltrate into the bile duct, which was alleviated after the treatment of MSCs (P<0.05). The serum level of total protein (TP) and albumin (ALB) in the model group were decreased compared with that of the control group, after treatment they significantly increased (P<0.05). The protein expressions of TNF-α and IFN-γ both in colon mucosa and in hepatic portal area up-regulated in the model group (P<0.05), and down-regulated in the treatment group compared with that in the control group (P<0.05). Conclusions: The data show that the activity of cholangitis is consistent with that of chronic colitis. MSCs may be a novel therapeutic drug for the treatment of cholangitis associated with chronic colitis.
Mo1719 Retesting for Latent Tuberculosis in Patients With Inflammatory Bowel Disease After Exposure to Biologics Pavol Papay, Christian Primas, Alexander Eser, Gottfried Novacek, Stefan Winkler, Sophie Frantal, Sieglinde Angelberger, Andrea Mikulits, Clemens Dejaco, Harald Vogelsang, Walter Reinisch BACKGROUND/AIM: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring for TB reactivation and/or infection in this risk group are lacking. METHODS: We retested consecutive patients with inflammatory bowel disease (IBD) under therapy with TNFi for a minimum of 5 months for LTB by interferon-γ release assay (IGRA) and tuberculin skin test (TST). From each subject a detailed patient history and concomitant therapy were captured. RESULTS: After a median of 34.9 weeks (20.7-177.7) IGRA was retested in 184/227 patients (81.1%; Crohn's disease n= 139, ulcerative colitis n=45) initially screened for LTB and subsequently treated with TNFi. Additionally TST was re-administered in 144/227 subjects (63.4%). The majority of patients was TNFi naïve (147/227, 79.9%). In 32 subjects isoniazid was provided prior and concurrently to TNFi due to LTB. In this subgroup retesting for LTB resulted in a reversion to negative in 6/13 patients (46.2%) and in 3/24 patients (12.5%, P=0.08) with a positive IGRA and positive TST at baseline, respectively. In patients without LTB at baseline no permanent IGRA conversion, but 6/144 (4.2%) TST conversions from negative to positive were observed. No single case of TB reactivation or infection was observed during the observation period. CONCLUSION: A conversion of IGRA during treatment with TNFi was not observed, but occurred for TST. IGRA frequently reverts to negative in patients with LTB after specific therapy and seems to be a sensitive method to monitor patients for LTB under treatment with TNFi.
Mo1722 High Body Mass Index and Asthma are Risk Factors Associated With Peristomal Pyoderma Gangrenosum Xianrui Wu, Saurabh Mukewar, Bo Shen Background: As an unusual variant of pyoderma gangrenosum, peristomal pyoderma gangrenosum (PPG) has been reported in small sample-sized studies. However, clinical features and risk factors for PPG are not well defined, and misdiagnosis is frequent. Aim: To compare stoma patients with or without PPG to identify clinical features as well as risk factors associated with development of PPG. Methods: We conducted an IRB-approved case-control study. Patients with a diagnosis of PPG were enrolled as cases, and the control group consisted of patients who had stoma construction but without pyoderma gangrenosum. Cases were obtained through searching the database of Cleveland Clinic using the “ICD 9” code from January 2008 to May 2011. The control group was selected by strictly matching on underlying diseases and type of stoma with a ratio of 3:1. Patients with pyoderma gangrenosum at other sites rather than peristomal area were excluded. Results: Eleven PPG patients were enrolled as cases (2 male and 9 female), all of them were biopsied for the purpose of exclusion. Mean age at the diagnosis of PPG was 41.9±14.0 years. Underlying disease was Crohn's disease (CD) for 6 patients, and ulcerative colitis (UC) for 5. Nine patients had end ileostomy, 1 had loop ileostomy, and 1 had colostomy. The time interval from the stoma construction to the diagnosis of PPG ranged from 14 days to 19.7 years. Two patients had a history of pyoderma gangrenosum at lower extremity, and the other two patients initially presented with PPG, but lower extremity got involved later. The largest diameter of PPG in this cohort was 15 cm. Eight patients had at least 1 relapse of PPG after initial healing, and a parallel course with PPG occurred in 2 patients. All 11 patients were locally injected with steroids, 8 of them needed systemic steroids, 6 needed immunosuppressive agents, and 4 patients need infliximab or adalimumab. After a median follow-up of 10.2 (range: 2.9-133.1) months, PPG healed in 7 patients and improved in 4 patients. Compared with control group, PPG patients were found to have higher body mass index (BMI), shorter duration of inflammatory bowel disease (IBD) and more concurrent asthma. However, no difference was found between the two groups in terms of age, gender, social status, extraintestinal manifestations, comorbidities, family history of IBD, history of stoma construction, preoperative drug use, duration of stoma, and stoma complication (p>0.05, Table). Conclusion: PPG can develop at any time after stoma construction in patients with underlying IBD,
Proportion of patients with IGRA / TST reversion with baseline positive IGRA or TST under isoniazid therapy Mo1720 Frequency and Chronology of Extraintestinal Manifestations in the Swiss Inflammatory Bowel Disease Cohort Stephan R. Vavricka, Claudine Gantenbein, Muriel Spoerri, Bettina M. Prinz Vavricka, Ekaterina Safroneeva, Alexander Navarini, Alain Schoepfer Background: Data on the frequency of extraintestinal manifestations (EIM) in inflammatory bowel disease (IBD) is scarce, especially the one evaluating the time of occurrence of the EIM relative to IBD diagnosis. Aim: To assess the type and frequency of EIM in IBD patients and to evaluate when EIMs occur relative to IBD diagnosis. Methods: Analysis of data from the Swiss Inflammatory Bowel Disease Cohort (SIBDCS) which collects data on a large
S-669
AGA Abstracts
AGA Abstracts
sample of IBD patients from hospitals and private practices across Switzerland starting in 2005. While parametric data are shown as mean ± SD, non-parametric data are presented as median and interquartile range (IQR). Results: A total of 1143 patients were analyzed (572 (50%) female, mean age 42.1 ± 14.4 years): 629 (55%) with Crohn's disease (CD), 501 (44%) with ulcerative colitis (UC), and 13 (1%) with indeterminate colitis (IC). Of 1143 patients, 374 (32.7%) presented with EIM (65% with CD, 33% with UC, 2% with IC). Of those patients suffering from EIMs, 37.4% presented with one, 41.7% with two, 12.4% with three, 5.3% with four, and 3.2% with five EIM during their lifetime. The IBD patients initially presented with the following EIMs: peripheral arthritis (PA) 63.4%, ankylosing spondylitis (AS) 8.1%, primary sclerosing cholangitis (PSC) 6.0%, uveitis 5.7%, oral aphthosis 5.7%, erythema nodosum (EN) 5.0%, pyoderma gangrenosum 1.8%, psoriasis 0.7%. While 92.9% of EIM occurred once IBD diagnosis was established (median 72 months, IQR 9-147 months, p < 0.001), 7.1% of EIMs preceded IBD diagnosis (median time 28 months before IBD diagnosis, IQR 7-60 months). Over a course of a lifetime, IBD patients presented with the following EIM (total exceeds 100 due to potential presence of multiple EIM): peripheral arthritis 69.3%, oral aphthosis 23%, ankylosing spondylitis 19.4%, uveitis 15.5%, erythema nodosum 14.5%, PSC 7.8%, pyoderma gangrenosum 6%, psoriasis 2.8%. Conclusion: EIMs frequently occur in a lifetime of IBD patients. The vast majority of patients present with EIMs once IBD diagnosis has been established. IBD patients most often present with peripheral arthritis, ankylosing spondylitis and PSC as their first EIM. However, peripheral arthritis, oral aphthosis, and ankylosing spondylitis are the most common EIMs in a lifetime of IBD patients.