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Sa1401 Patients With Mild Enteropathy Have Apoptotic Injury of Enterocytes Similar to That in Advanced Enteropathy in Celiac Disease: Implications on the Treatment
Sa1399
of early immunological insult at mucosal level, raising serious questions on the existing practice of not treating patients with mild enteropathy with gluten free diet. Table 1: Expression of different markers of apoptosis and cell regeneration in the duodenal mucosal biopsies as a whole of patients with early enteropathy, advanced enteropathy and controls
AGA Abstracts
Soluble Syndecan-1: A Potential Novel Biomarker of Small Bowel Mucosal Damage in Children With Celiac Disease Doron Yablecovitch, Asaf Oren, Shomron Ben-Horin, Ella Fudim, Abraham R. Eliakim, Fred M. Konikoff, Uri Kopylov, Aaron Lerner INTRODUCTION: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1( SSDC1) levels, is highly regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 level and mucosal damage in CD has not been evaluated. OBJECTIVES: To compare serum levels of SSDC1 in children with CD to healthy controls and to determine its relationship with histological grading classified by modified Marsh criteria. METHODS: Cross-sectional, pilot study, in which serum concentrations of SSDC1 were analyzed by ELISA in a cohort of 49 consecutive untreated children with CD and 15 healthy controls. CD was diagnosed based on positive celiac serology (antitissue transglutaminase antibodies and/or anti endomysial antibodies or DGP) and small intestinal biopsy. SSDC1 levels at the time of biopsy were compared with Marsh grading. Controls were defined by abdominal pain, negative celiac serology, normal upper endoscopy and normal small intestinal biopsies. RESULTS: Soluble syndecan-1 levels were significantly higher in CD patients compared to healthy controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p<0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to healthy controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p <0.05). SSDC1 concentrations displayed significant correlation with mucosal damage defined by Marsh (r=0.39, p<0.05). SSDC1 levels of 80 ng/ml yielded a sensitivity of 29% and specificity of 100%. The positive predictive value was 100% whereas negative predictive value was 30%. CONCLUSION: This is the first study demonstrating elevated levels of serum soluble syndecan-1 in patients with celiac disease compare to healthy controls. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a diagnostic and a surrogate biomarker in CD remains to be determined.
Values are expressed as H score, calculated by multiplying the area of staining & stain intensity in a specific
Sa1400 Impact of Clostridium difficile Infection on Hospitalized Adults with Celiac Disease Sushil Kumar Garg, Vaibhav Wadhwa, Sahil Khanna BACKGROUND: Clostridium difficile infection (CDI) is associated with poor outcomes in hospitalized adults. Patients with severe Celiac disease may be hospitalized for diarrhea, dehydration and failure to thrive and are predisposed to CDI. We examined the rates and health-care outcomes of CDI in patients with Celiac disease. METHODS: We performed a cross-sectional analysis using 2012 Nationwide Inpatient Sample data. International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes were used to identify patients with Celiac disease (ICD-9: 579.0) and CDI (ICD-9: 008.45). Primary outcome variables included inpatient mortality, length of stay and total charges in patients with celiac disease with or without CDI. Secondary outcomes included acute renal failure. Univariate and multivariable logistic regression (for categorical variables) and linear regression (for continuous variables) were performed. Multiple variable regression analysis controlled for differences in sex, age, race, location of hospital (rural versus urban), patient residence, insurance, hospital size, overall geographical region, co-morbidities, weekend admission, type of admission and type of hospital (teaching vs not). RESULTS: Of 6851 patients with Celiac disease 72% female) and 118 had CDI (1.72%). In patients with Celiac disease, the overall all cause in hospital mortality was 1.3%, average length of stay was 4.9 days, average hospital charges were $38,382.71. On multiple variable regression analyses, patients with celiac disease and CDI had longer LOS (8.8 vs 4.8 d; p < 0.001), and greater hospital charges ($ 68,541 vs $38,382; p < 0.001) compared to patients with Celiac disease without CDI. Patients with CDI and Celiac disease had increased odds of acute renal failure (adjusted odds ratio, 2.5; 95 % CI (1.44 - 4.34). There were no differences in mortality in the two groups. CONCLUSIONS: In patients with Celiac disease, CDI is an uncommon complication but is associated with greater LOS, total charges and acute renal failure.
Figure 1. Photomicrographs show cytoplasmic granular expression of M30 in the duodenal biopsy of controls [Figure A x 100], mild enteropathy [Figure B x 100] and advanced enteropathy Celiac disease (arrows) [Figure C x 200]. H2AX stain shows nuclear positivity in the controls [Figure D x 40], mild enteropathy [Figure E x 200] and advanced enteropathy Celiac disease (arrows) [Figure F x 100].
Sa1402 Celiac Disease is Rare in Post Roux-en-Y Gastric Bypass Patients Pichamol Jirapinyo, Austin L. Chiang, Aoife Devery, Michele B. Ryan, Christopher C. Thompson Background: Abdominal discomfort is a common presentation in patients with Roux-en-Y gastric bypass (RYGB). In the majority of cases, the etiology remains unknown. Given the prevalence of celiac disease (CD), it has been hypothesized that there may be an association between CD and abdominal symptoms in RYGB patients. Aims: To determine the prevalence of CD in the RYGB population and how it differs from the general obese population. Methods: Design: A retrospective database review. Methods: The Research Patient Data Registry (RPDR) from two academic institutions from 2005 to 2015 was used to create a database of patients with obesityand history of RYGB, with and without CD. Patient demographics, body mass index (BMI) and comorbidities were then obtained via detailed chart review. Results: Of 236,175 obese patients, 1,222 had CD. This represented a prevalence of 0.52%. Of the 236,175 obese patients, 8,972 underwent RYGB. Of these, 2,972 (33.1%) suffered from abdominal pain and other symptoms. 340 out of 2,972 were found to have marginal ulceration (MU). Of the remaining 2,632 RYGB patients with unexplained abdominal pain, 638 patients were tested for CD using tissue transglutaminase antibody (tTG) IgA. There were 15 confirmed CD cases representing a prevalence of 0.17% among the RYGB group. This is significantly lower ( p < 0.05) than the prevalence in the obese (0.52%) and general populations (1-2%). Of the 15 RYGB patients with confirmed CD, 93% were female with an average age of 41±9. 69% were diagnosed of CD prior to their gastric bypass. BMI at the time of diagnosis was 35.91±7.21 kg/m2. 40%, 40%, 66.7% had iron deficiency anemia, vitamin B12 deficiency and vitamin D deficiency, respectively. Of the 623 RYGB patients who were tested negative for CD, 90% were female with an average of 49±12. BMI at the time of CD testing was 35.2±8.3 kg/m2. 45.9%, 22.1%, 64.3% had iron deficiency anemia, vitamin B12 deficiency and vitamin D deficiency, respectively. Conclusion: The prevalence of CD in the obese population is substantially less than that found in the general population. Furthermore, the prevalence of CD was significantly less in patients that had surgery for morbid obesity than in obese patients that did not undergo bariatric surgery. Further studies are needed to better understand the relationship between CD and obesity.
Sa1401 Patients With Mild Enteropathy Have Apoptotic Injury of Enterocytes Similar to That in Advanced Enteropathy in Celiac Disease: Implications on the Treatment Prasenjit Das, Gaurav PS Gahlot, Archita Makharia, Anil Verma, Vineet Ahuja, Siddhartha Datta Gupta, Govind K. Makharia Objectives Severity of villous atrophy in celiac disease (CeD) is a trade-off between enterocyte loss and cell regeneration. A positive effect of gluten-free diet has recently been shown in patients with mild enteropathy. We explored the apoptotic enterocyte loss-cell regenerative activities in mild enteropathy CeD, versus those with advanced enteropathy and normal duodenal biopsies. Methods Duodenal biopsies from patients with positive anti-tissue transglutaminase antibody having mild enteropathy (Marsh grade 0&1)(n=26), advanced enteropathy (Marsh grade ‡2)(n=41) and 12 controls were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-score based on the intensity and distribution of markers was compared. Results End-apoptotic markers (M30 and H2AX) as well as a marker of cell death (perforin) were significantly up-regulated both in biopsies of mild and advanced enteropathies, in comparison to controls when compared separately, with no significant difference between the for two. Ki67 labeling index, while, was significantly upregulated in mild enteropathy, in the advanced enteropathy, Ki67 index was significantly lower. Conclusions Even in patients with mild enteropathy, rate of apoptotic enterocyte loss was similar to that with advanced enteropathy. In mild enteropathy, increased crypt regeneration, possibly is responsible for maintenance of villous height, while in the advanced disease crypt regenerative activity fails, resulting in atrophy. This is the first objective evidence
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AGA Abstracts
of early immunological insult at mucosal level, raising serious questions on the existing practice of not treating patients with mild enteropathy with gluten free diet. Table 1: Expression of different markers of apoptosis and cell regeneration in the duodenal mucosal biopsies as a whole of patients with early enteropathy, advanced enteropathy and controls
AGA Abstracts
Soluble Syndecan-1: A Potential Novel Biomarker of Small Bowel Mucosal Damage in Children With Celiac Disease Doron Yablecovitch, Asaf Oren, Shomron Ben-Horin, Ella Fudim, Abraham R. Eliakim, Fred M. Konikoff, Uri Kopylov, Aaron Lerner INTRODUCTION: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1( SSDC1) levels, is highly regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 level and mucosal damage in CD has not been evaluated. OBJECTIVES: To compare serum levels of SSDC1 in children with CD to healthy controls and to determine its relationship with histological grading classified by modified Marsh criteria. METHODS: Cross-sectional, pilot study, in which serum concentrations of SSDC1 were analyzed by ELISA in a cohort of 49 consecutive untreated children with CD and 15 healthy controls. CD was diagnosed based on positive celiac serology (antitissue transglutaminase antibodies and/or anti endomysial antibodies or DGP) and small intestinal biopsy. SSDC1 levels at the time of biopsy were compared with Marsh grading. Controls were defined by abdominal pain, negative celiac serology, normal upper endoscopy and normal small intestinal biopsies. RESULTS: Soluble syndecan-1 levels were significantly higher in CD patients compared to healthy controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p<0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to healthy controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p <0.05). SSDC1 concentrations displayed significant correlation with mucosal damage defined by Marsh (r=0.39, p<0.05). SSDC1 levels of 80 ng/ml yielded a sensitivity of 29% and specificity of 100%. The positive predictive value was 100% whereas negative predictive value was 30%. CONCLUSION: This is the first study demonstrating elevated levels of serum soluble syndecan-1 in patients with celiac disease compare to healthy controls. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a diagnostic and a surrogate biomarker in CD remains to be determined.
Values are expressed as H score, calculated by multiplying the area of staining & stain intensity in a specific
Sa1400 Impact of Clostridium difficile Infection on Hospitalized Adults with Celiac Disease Sushil Kumar Garg, Vaibhav Wadhwa, Sahil Khanna BACKGROUND: Clostridium difficile infection (CDI) is associated with poor outcomes in hospitalized adults. Patients with severe Celiac disease may be hospitalized for diarrhea, dehydration and failure to thrive and are predisposed to CDI. We examined the rates and health-care outcomes of CDI in patients with Celiac disease. METHODS: We performed a cross-sectional analysis using 2012 Nationwide Inpatient Sample data. International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) codes were used to identify patients with Celiac disease (ICD-9: 579.0) and CDI (ICD-9: 008.45). Primary outcome variables included inpatient mortality, length of stay and total charges in patients with celiac disease with or without CDI. Secondary outcomes included acute renal failure. Univariate and multivariable logistic regression (for categorical variables) and linear regression (for continuous variables) were performed. Multiple variable regression analysis controlled for differences in sex, age, race, location of hospital (rural versus urban), patient residence, insurance, hospital size, overall geographical region, co-morbidities, weekend admission, type of admission and type of hospital (teaching vs not). RESULTS: Of 6851 patients with Celiac disease 72% female) and 118 had CDI (1.72%). In patients with Celiac disease, the overall all cause in hospital mortality was 1.3%, average length of stay was 4.9 days, average hospital charges were $38,382.71. On multiple variable regression analyses, patients with celiac disease and CDI had longer LOS (8.8 vs 4.8 d; p < 0.001), and greater hospital charges ($ 68,541 vs $38,382; p < 0.001) compared to patients with Celiac disease without CDI. Patients with CDI and Celiac disease had increased odds of acute renal failure (adjusted odds ratio, 2.5; 95 % CI (1.44 - 4.34). There were no differences in mortality in the two groups. CONCLUSIONS: In patients with Celiac disease, CDI is an uncommon complication but is associated with greater LOS, total charges and acute renal failure.
Figure 1. Photomicrographs show cytoplasmic granular expression of M30 in the duodenal biopsy of controls [Figure A x 100], mild enteropathy [Figure B x 100] and advanced enteropathy Celiac disease (arrows) [Figure C x 200]. H2AX stain shows nuclear positivity in the controls [Figure D x 40], mild enteropathy [Figure E x 200] and advanced enteropathy Celiac disease (arrows) [Figure F x 100].
Sa1402 Celiac Disease is Rare in Post Roux-en-Y Gastric Bypass Patients Pichamol Jirapinyo, Austin L. Chiang, Aoife Devery, Michele B. Ryan, Christopher C. Thompson Background: Abdominal discomfort is a common presentation in patients with Roux-en-Y gastric bypass (RYGB). In the majority of cases, the etiology remains unknown. Given the prevalence of celiac disease (CD), it has been hypothesized that there may be an association between CD and abdominal symptoms in RYGB patients. Aims: To determine the prevalence of CD in the RYGB population and how it differs from the general obese population. Methods: Design: A retrospective database review. Methods: The Research Patient Data Registry (RPDR) from two academic institutions from 2005 to 2015 was used to create a database of patients with obesityand history of RYGB, with and without CD. Patient demographics, body mass index (BMI) and comorbidities were then obtained via detailed chart review. Results: Of 236,175 obese patients, 1,222 had CD. This represented a prevalence of 0.52%. Of the 236,175 obese patients, 8,972 underwent RYGB. Of these, 2,972 (33.1%) suffered from abdominal pain and other symptoms. 340 out of 2,972 were found to have marginal ulceration (MU). Of the remaining 2,632 RYGB patients with unexplained abdominal pain, 638 patients were tested for CD using tissue transglutaminase antibody (tTG) IgA. There were 15 confirmed CD cases representing a prevalence of 0.17% among the RYGB group. This is significantly lower ( p < 0.05) than the prevalence in the obese (0.52%) and general populations (1-2%). Of the 15 RYGB patients with confirmed CD, 93% were female with an average age of 41±9. 69% were diagnosed of CD prior to their gastric bypass. BMI at the time of diagnosis was 35.91±7.21 kg/m2. 40%, 40%, 66.7% had iron deficiency anemia, vitamin B12 deficiency and vitamin D deficiency, respectively. Of the 623 RYGB patients who were tested negative for CD, 90% were female with an average of 49±12. BMI at the time of CD testing was 35.2±8.3 kg/m2. 45.9%, 22.1%, 64.3% had iron deficiency anemia, vitamin B12 deficiency and vitamin D deficiency, respectively. Conclusion: The prevalence of CD in the obese population is substantially less than that found in the general population. Furthermore, the prevalence of CD was significantly less in patients that had surgery for morbid obesity than in obese patients that did not undergo bariatric surgery. Further studies are needed to better understand the relationship between CD and obesity.
Sa1401 Patients With Mild Enteropathy Have Apoptotic Injury of Enterocytes Similar to That in Advanced Enteropathy in Celiac Disease: Implications on the Treatment Prasenjit Das, Gaurav PS Gahlot, Archita Makharia, Anil Verma, Vineet Ahuja, Siddhartha Datta Gupta, Govind K. Makharia Objectives Severity of villous atrophy in celiac disease (CeD) is a trade-off between enterocyte loss and cell regeneration. A positive effect of gluten-free diet has recently been shown in patients with mild enteropathy. We explored the apoptotic enterocyte loss-cell regenerative activities in mild enteropathy CeD, versus those with advanced enteropathy and normal duodenal biopsies. Methods Duodenal biopsies from patients with positive anti-tissue transglutaminase antibody having mild enteropathy (Marsh grade 0&1)(n=26), advanced enteropathy (Marsh grade ‡2)(n=41) and 12 controls were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-score based on the intensity and distribution of markers was compared. Results End-apoptotic markers (M30 and H2AX) as well as a marker of cell death (perforin) were significantly up-regulated both in biopsies of mild and advanced enteropathies, in comparison to controls when compared separately, with no significant difference between the for two. Ki67 labeling index, while, was significantly upregulated in mild enteropathy, in the advanced enteropathy, Ki67 index was significantly lower. Conclusions Even in patients with mild enteropathy, rate of apoptotic enterocyte loss was similar to that with advanced enteropathy. In mild enteropathy, increased crypt regeneration, possibly is responsible for maintenance of villous height, while in the advanced disease crypt regenerative activity fails, resulting in atrophy. This is the first objective evidence
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Page 305
AGA Abstracts