- Email: [email protected]
Prevalence, Causes and Characteristics of Nonresponsive Celiac Disease
AGA Abstracts
who had tried GF Cheerios, a minority of NCGS patients (47%) reported no adverse reaction, compared to a majority of CD patients (63%, p=0.02). Significantly more subjects in the NCGS group avoid genetically modified foods (NCGS 47%; CD 28%, p<0.0001), attempt to only eat organic foods (NCGS 29%; CD: 12%, p<0.0001), believe a GF diet improves energy and concentration (NCGS 40%; CD 21%, p<.0001) and believe that gluten is bad for everyone (NCGS 31%; CD 16%, p<0.0001). After adjusting for age and gender, the following factors were associated with the belief that not all vaccines are safe for people with celiac disease: NCGS (OR comp. to CD 1.47; 95% CI 1.06 - 2.06), belief that a GF diet improves energy and concentration (OR 2.60; 95% CI 1.57-2.72), feeling depressed due to CD/NCGS (OR 1.41; 95% CI 1.05-1.90), avoidance of GMO foods (OR 1.85; 95% CI 1.39-2.47), and trying to eat only organic products (OR 1.54; 95% CI 1.07-2.21). Conclusions: In this population with gluten-related disorders, misperceptions regarding gluten are pervasive. More than 25% have doubts about vaccine safety for patients with CD despite a lack of evidence for this assertion. Subjects with NCGS are more likely than those with CD to doubt vaccine safety, report an adverse reaction after eating GF Cheerios, and to believe in the value of GMO and organic foods and that gluten is bad for everyone. Concerns regarding a lack of reliable information on gluten and its content in food and medications may lead to or reinforce beliefs that result in a detriment to public health.
Su1134 CELIAC DISEASE PATIENTS PRACTICING A GLUTEN-FREE DIET STILL CONSUME UNSAFE LEVELS OF GLUTEN Jack A. Syage, Matthew A. Dickason, Jennifer A. Sealey Voyksner Figure. Plot of frequency and severity (scale from 0 to 10) of abdominal pain symptoms and the corresponding average gluten ingestions for each severity value.
BACKGROUND: Individuals with diagnosed celiac disease (CD) must adhere to a life-long gluten-free diet (GFD). Yet in practice it is virtually impossible to totally avoid gluten and as such, patients are often exposed to low levels of gluten that can cause symptomatic pain and suffering and persistent in histologic damage that can cause other long-term health issues. In this study we estimate how much gluten is accidentally consumed while on a GFD. This work informs individuals with CD how much gluten they are ingesting and establishes what level of protection is necessary for therapies in development. METHODS: A meta-analysis was conducted combining clinical study results from (i) measurements of gluten in urine[1] and feces[2] in non-CD and CD populations, and (ii) trial effect and symptom results for the ALV003-1221 study. The measurements of gluten in urine and feces were accompanied with controlled measurements of gluten exposure utilizing a gluten challenge. A calibration factor was then applied that allowed computing normal ingestion of gluten from the urine and feces measurements. A second analysis involved estimating the amount of gluten that was removed from the diets in the ALV003-1221 study, which led to improved histology even for the placebo group (trial effect). We will present how the frequency and quantity (distribution) of gluten intrusion was determined and correlated with the frequency and severity of abdominal pain. RESULTS: The average inadvertent exposure of gluten by CD individuals on a GFD was estimated to be approximately 100 mg/day, as measured by the urine test and 300-500 mg/day as measured by the feces test (Table for feces only). The analyses of the ALV003-1221 data for CD individuals with moderate to severe symptoms indicate that CD patients ingest approximately 500-600 mg/ day of gluten. The distribution of gluten ingestion events by weight (Figure) is such that the most common symptomatic severity is mild (3 on a scale of 0 to 10) and comprises 30% of all symptomatic events and corresponds to <400 mg ingestion. Severe symptoms correspond to about 1 g ingestion, which comprises <5% of symptomatic events. An unintended 2 g intrusion occurs in <1% of symptomatic events by this analysis. CONCLUSION: These results demonstrate that individuals on a GFD do experience gluten intrusions and the quantity of gluten ingested is sufficient to trigger symptomatic responses and may ultimately result in persistent histologic damage. Potential therapies that would safeguard against up to 2 g of unintentional gluten ingestion will protect CD patients from approximately 99% of potential symptomatic events. [1] Moreno ML, Cebolla A, Munoz-Suano A et al. Gut 2015; doi:10.1136/gutjnl-2015-310148. [2] Comino I, Fernandez-Banares F, Esteve E, et al., Am J Gastroenterol 2016; 111:1456-1465.
Su1135 PREVALENCE, CAUSES AND CHARACTERISTICS OF NONRESPONSIVE CELIAC DISEASE Mariana Urquiaga, Abhijeet Yadav, John Mark B. Gubatan, Brisas Flores, Shreya Amin, Katerina Byanova, Javier A. Villafuerte-Galvez, Satya Kurada, Daniel Leffler, Ciaran P. Kelly Background As many as 30% of subjects with celiac disease (CD) fail to respond to a gluten free diet (GFD). These subjects are classified as having nonresponsive celiac disease (NRCD). The cause for persistent signs and/or symptoms compatible with CD is most frequently inadvertent gluten exposure. However, a number of conditions can complicate celiac disease and identification of the cause of NRCD is important for appropriate management. Aim To utilize a large cohort of NRCD patients to improve our understanding of this condition. Methods We performed a retrospective review of all patients in our prospectively kept CD database between 2007 and June 2016 for NRCD. NRCD was defined as patients with biopsy proven CD who had either ongoing or recurrent symptoms despite being on a GFD for at least 6 months. We excluded those who had only one clinic visit for evaluation of NRCD. Results Five hundred and three patients out of 1981 CD cases met our criteria for NRCD, for an overall prevalence in the cohort of 25.4%. Gastrointestinal symptoms were the most common complaint, present in 86.5%, followed by fatigue in 29%, weight loss in 20.5%, anemia in 17.1% and dermatitis herpetiformis in 5.2%. The median time of follow up for these patients was 3.1 years (range 0.1-17). As previously described, inadvertent gluten exposure was the most common cause, however over 15 different etiologies were identified. (Figure 1) Table 2 shows characteristics of our NRCD cohort compared to patients responsive to the GFD. Of these characteristics, the duration of the GFD, being referred from another institution and the presence of depression or anxiety were each found to be significantly associated with NRCD (p < 0.005 for each). Conclusion NRCD is a common problem and although gluten ingestion is the most common cause there are a multitude other causes. A shorter duration of GFD adherence is an important factor probably reflecting lack of experience with the diet. NRCD is a common reason for referral to a specialized celiac center. Depression and anxiety should be diagnosed and treated in nonresponsive patients as they are possible contributors to symptoms. Given the frequency which with NRCD occurs and the breadth of etiologies it is important for clinicians to follow the diagnostic algorithms that have been developed to efficiently identify specific etiologies for their patients to guide their management. Table 1
Table. Gluten consumption as measured in feces.
Medians are compared with Wilcoxon rank-sum test and frequencies with Chi-square test. *Two patients were diagnosed with small-intestinal lymphoma on initial evaluation. **Data was available for 270 nonresponsive and 407 responsive patients.
AGA Abstracts
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Su1138 GENDER-BASED DIFFERENCES IN UNDIAGNOSED CELIAC DISEASE: SUBTLER THAN IMAGINED Claire Jansson-Knodell, RokSon Choung, Katherine S. King, Joseph J. Larson, Carol T. Van Dyke, Tricia Brantner, Alberto Rubio-Tapia, Joseph A. Murray
Figure 1 Since more than one diagnosis was made in some patients the total number of etiologies adds up to more than 100%. *Includes type 1 and type 2 refractory CD, ulcerative jejunitis and small intestinal lymphoma. **Includes eosinophilic esophagitis (3), drugs side effects (3), duodenal adenocarcinoma (2), cirrhosis complications (2), esophageal motility disorders (1), post-surgical adhesions (1), dumping syndrome (1), common variable immunodeficiency (1), rectal prolapse (1), fibromyalgia (1), microsporidiasis (1), pyloric stenosis(1) and a post-partum flair (1).
INTRODUCTION: The impact of undiagnosed celiac disease on women's health is unclear. There is a paucity of research focused on gender-based differences in undiagnosed populations with celiac disease. The objective of this study was to estimate gender-based differences in a community-based cohort of patients seropositive for celiac disease with respect to 1) age, 2) anthropomorphic measurements, and 3) associated autoimmune diseases. METHODS: Stored serum from a community-based sample of 30,425 people, aged 18-49 years old residing in a Minnesota county was tested for celiac disease using tissue transglutaminase (TTG) and endomysial antibody (EMA) between 2006 and 2011. Clinical data were systematically abstracted from the electronic medical record of patients who were seropositive for celiac disease defined as both TTG-IgA and EMA positive testing. Categorical data were analyzed with Chi-square and Fisher's exact test. Age was studied with the equal variance T-test. RESULTS: In this community-based cohort, 338 (1.1%) subjects were identified with undiagnosed celiac disease or celiac disease autoimmunity. That group was comprised of 213 females (prevalence 1.2%) and 125 males (prevalence 0.98%) (p=0.07). A representative sample of those with celiac disease autoimmunity showed that seropositive women were younger with an average age of 33.8 years compared to 37.4 years in their male counterparts (p=0.002); the average age of individuals tested was 34.9 years in women and 36.4 years in men. Women in the seropositive group had a lower average body mass index (BMI) of 26.2 versus 28.1 in men (p=0.028) as seen in the baseline characteristics table. Concurrent autoimmune diseases were recorded in 36 of the females and 25 of the males (females 20.6%; males 24.8%; p=0.42). Depression was more common in seropositive females than males (females 27.7%; males 9.8%, p=0.0004). DISCUSSION: Celiac disease is common. The finding of frequent seropositive individuals emphasizes the importance of awareness of undiagnosed celiac disease. These data indicate the potential of gender-based differences in terms of age at detection, anthropometric measurements where >50% are overweight or obese, and associated diseases that can co-occur with celiac disease. Surprisingly, males with celiac disease autoimmunity were just as likely as females to have an autoimmune disease. These results may have clinical implications for uncovering cases of celiac disease and once identified, managing them comprehensively. Sample of Undiagnosed Celiac Cases
Su1136 NO DETRIMENTAL EFFECT OF OATS ON SYMPTOMS, HISTOLOGICAL PARAMETERS, SEROLOGICAL TESTS, OR QUALITY OF LIFE IN CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS María Inés Pinto Sanchez, Natalia Causada Calo, Alexander C. Ford, Joseph A. Murray, Premysl Bercik, Paul Moayyedi, Elena F. Verdu, Peter H. R. Green Background: Current management of celiac disease (CD) is a life-long gluten free diet (GFD) that excludes wheat, rye, and barley. Oats may increase the nutritional value of a GFD, but their use remains controversial due to reports on oat intolerance in some patients. Objectives: To perform a systematic review and meta-analysis to assess the evidence on safety of oat consumption as a part of a GFD for patients with CD and DH. Selection criteria: We included clinical trials and observational studies evaluating the effect of oats within a GFD on symptoms, serological, and histological responses in patients with CD, using electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), and SIGLE. Two authors collected the data independently. GRADE approach was used for quality of the body of evidence. Results: 422 studies were identified and 32 were eligible for analysis. 16/32 papers were clinical trials, 6 randomized control trials (RCT; 3 in children, 3 in adults), 2 non-RCTs and 8 post hoc reports from RCTs. A meta-analysis was performed in 6 RCTs; none evaluated DH. All RCTs involved pure/uncontaminated oats. There was no difference in gastrointestinal symptoms in adult CD patients treated with GFD with or without oats for 12 months (standardized mean difference (SMD) -0.22; 95% confidence interval (CI) -0.56 to 0.13; P=0.22). The quality of evidence was very low. 16 studies (5 RCTs) evaluated the histological response to oats in patients with CD for 12 months, and no differences in histological indices were observed between groups (SMD: -0.0; 95% CI -0.01 to 0.01; P=0.92). Similar proportions of patients in both groups had histological remission after treatment (relative risk (RR) 0.24; 95% CI 0.01-4.8; P=0.35). The quality of evidence was low. Based on low to moderate quality evidence, there was no difference in intraepithelial lymphocyte counts in patients on a GFD with and without oats (SMD: 0.21; 95% CI -1.44 to 1.86). Subgroup analysis on adult patients vs. children did not reveal any differences. There was no difference in serological response measured by tTG (RR 1.71; 95% CI 0.62-4.71; P=0.89); EmA (RR 1.45; 95% CI 0.77-2.74; P=0.25) or antigliadin antibodies in patients on a GFD with or without oats. The studies in adults were of lower quality. No difference in quality of life was observed between patients consuming or not consuming oats (SMD-2.5; 95%CI -13.86 to 8.86; P=0.67). The quality of evidence was very low. Conclusions: We could not find evidence that oats have detrimental effects on the key outcomes assessed in this study in patients with CD on a GFD. However, there were few studies for many of the endpoints, and the quality of evidence was low. Rigorous double-blind placebo-controlled RCTs are needed to evaluate the effect of oat consumption as part of a GFD in patients with CD.
Su1137 ASPERGILLUS NIGER-DERIVED ENZYME DEGRADES GLUTEN IN THE STOMACH OF GLUTEN-SENSITIVE SUBJECTS Julia König, Savanne Holster, Maaike J Bruins, Robert J. Brummer Rationale: Gluten may cause gastrointestinal complaints in individuals sensitive to gluten. Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten into non-immunogenic compounds in an in vivo setting in healthy subjects in which AN-PEP was added to a liquid, intragastrically infused meal1. The current study investigated the efficacy of AN-PEP to degrade gluten in a physiological meal setting in gluten-sensitive subjects. Methods: In this randomized placebo-controlled cross-over study, 18 self-reported gluten-sensitive subjects attended three test days. A multilumen nasoduodenal feeding catheter was placed to collect gastric and duodenal aspirates. Subjects consumed a porridge containing approximately 0.5 g gluten in the form of two crumbled wheat cookies as well as two tablets either containing 160 000 PPI of AN-PEP (high dose), or 80 000 PPI (low dose), or placebo in a double-blinded, randomized manner. Gastric and duodenal content was sampled at several time points over 180 minutes and analysed for gluten epitopes using the Gluten-Tec® ELISA. The 180-min areas under the curve (AUC) of epitope concentration were calculated using curve fitting. Additionally, participants were asked to fill in questionnaires (GSRS) after each test day. The non-parametric Wilcoxon signed-ranked paired test at α=0.05 with a Bonferroni correction was used to detect significant differences. Results: AN-PEP significantly lowered the gluten concentrations in the stomach and in the duodenum
S-481
AGA Abstracts
AGA Abstracts
compared to the placebo in both the high dose and the low dose. In the stomach, gluten levels were reduced from 218 ± 155 µgxmin/ml (mean ± STD) in the placebo to 31 ± 24 µgxmin/ml in the high dose (p=0.001) and to 31 ± 22 µgxmin/ml in the low dose (p=0.001). In the duodenum, gluten levels were reduced from 65 ± 88 µgxmin/ml in the placebo to 12 ± 13 µgxmin/ml in the high dose (p=0.019) and to 8 ± 5 µgxmin/ml in the low dose (p=0.015). Conclusions: Even in a physiological meal setting, AN-PEP significantly degraded most gluten before it entered the duodenum in self-reported gluten-sensitive subjects. In those subjects, the consumption of AN-PEP was well tolerated. 1) Salden et al. Aliment Pharmacol Ther 2015; 42:273-285.
who had tried GF Cheerios, a minority of NCGS patients (47%) reported no adverse reaction, compared to a majority of CD patients (63%, p=0.02). Significantly more subjects in the NCGS group avoid genetically modified foods (NCGS 47%; CD 28%, p<0.0001), attempt to only eat organic foods (NCGS 29%; CD: 12%, p<0.0001), believe a GF diet improves energy and concentration (NCGS 40%; CD 21%, p<.0001) and believe that gluten is bad for everyone (NCGS 31%; CD 16%, p<0.0001). After adjusting for age and gender, the following factors were associated with the belief that not all vaccines are safe for people with celiac disease: NCGS (OR comp. to CD 1.47; 95% CI 1.06 - 2.06), belief that a GF diet improves energy and concentration (OR 2.60; 95% CI 1.57-2.72), feeling depressed due to CD/NCGS (OR 1.41; 95% CI 1.05-1.90), avoidance of GMO foods (OR 1.85; 95% CI 1.39-2.47), and trying to eat only organic products (OR 1.54; 95% CI 1.07-2.21). Conclusions: In this population with gluten-related disorders, misperceptions regarding gluten are pervasive. More than 25% have doubts about vaccine safety for patients with CD despite a lack of evidence for this assertion. Subjects with NCGS are more likely than those with CD to doubt vaccine safety, report an adverse reaction after eating GF Cheerios, and to believe in the value of GMO and organic foods and that gluten is bad for everyone. Concerns regarding a lack of reliable information on gluten and its content in food and medications may lead to or reinforce beliefs that result in a detriment to public health.
Su1134 CELIAC DISEASE PATIENTS PRACTICING A GLUTEN-FREE DIET STILL CONSUME UNSAFE LEVELS OF GLUTEN Jack A. Syage, Matthew A. Dickason, Jennifer A. Sealey Voyksner Figure. Plot of frequency and severity (scale from 0 to 10) of abdominal pain symptoms and the corresponding average gluten ingestions for each severity value.
BACKGROUND: Individuals with diagnosed celiac disease (CD) must adhere to a life-long gluten-free diet (GFD). Yet in practice it is virtually impossible to totally avoid gluten and as such, patients are often exposed to low levels of gluten that can cause symptomatic pain and suffering and persistent in histologic damage that can cause other long-term health issues. In this study we estimate how much gluten is accidentally consumed while on a GFD. This work informs individuals with CD how much gluten they are ingesting and establishes what level of protection is necessary for therapies in development. METHODS: A meta-analysis was conducted combining clinical study results from (i) measurements of gluten in urine[1] and feces[2] in non-CD and CD populations, and (ii) trial effect and symptom results for the ALV003-1221 study. The measurements of gluten in urine and feces were accompanied with controlled measurements of gluten exposure utilizing a gluten challenge. A calibration factor was then applied that allowed computing normal ingestion of gluten from the urine and feces measurements. A second analysis involved estimating the amount of gluten that was removed from the diets in the ALV003-1221 study, which led to improved histology even for the placebo group (trial effect). We will present how the frequency and quantity (distribution) of gluten intrusion was determined and correlated with the frequency and severity of abdominal pain. RESULTS: The average inadvertent exposure of gluten by CD individuals on a GFD was estimated to be approximately 100 mg/day, as measured by the urine test and 300-500 mg/day as measured by the feces test (Table for feces only). The analyses of the ALV003-1221 data for CD individuals with moderate to severe symptoms indicate that CD patients ingest approximately 500-600 mg/ day of gluten. The distribution of gluten ingestion events by weight (Figure) is such that the most common symptomatic severity is mild (3 on a scale of 0 to 10) and comprises 30% of all symptomatic events and corresponds to <400 mg ingestion. Severe symptoms correspond to about 1 g ingestion, which comprises <5% of symptomatic events. An unintended 2 g intrusion occurs in <1% of symptomatic events by this analysis. CONCLUSION: These results demonstrate that individuals on a GFD do experience gluten intrusions and the quantity of gluten ingested is sufficient to trigger symptomatic responses and may ultimately result in persistent histologic damage. Potential therapies that would safeguard against up to 2 g of unintentional gluten ingestion will protect CD patients from approximately 99% of potential symptomatic events. [1] Moreno ML, Cebolla A, Munoz-Suano A et al. Gut 2015; doi:10.1136/gutjnl-2015-310148. [2] Comino I, Fernandez-Banares F, Esteve E, et al., Am J Gastroenterol 2016; 111:1456-1465.
Su1135 PREVALENCE, CAUSES AND CHARACTERISTICS OF NONRESPONSIVE CELIAC DISEASE Mariana Urquiaga, Abhijeet Yadav, John Mark B. Gubatan, Brisas Flores, Shreya Amin, Katerina Byanova, Javier A. Villafuerte-Galvez, Satya Kurada, Daniel Leffler, Ciaran P. Kelly Background As many as 30% of subjects with celiac disease (CD) fail to respond to a gluten free diet (GFD). These subjects are classified as having nonresponsive celiac disease (NRCD). The cause for persistent signs and/or symptoms compatible with CD is most frequently inadvertent gluten exposure. However, a number of conditions can complicate celiac disease and identification of the cause of NRCD is important for appropriate management. Aim To utilize a large cohort of NRCD patients to improve our understanding of this condition. Methods We performed a retrospective review of all patients in our prospectively kept CD database between 2007 and June 2016 for NRCD. NRCD was defined as patients with biopsy proven CD who had either ongoing or recurrent symptoms despite being on a GFD for at least 6 months. We excluded those who had only one clinic visit for evaluation of NRCD. Results Five hundred and three patients out of 1981 CD cases met our criteria for NRCD, for an overall prevalence in the cohort of 25.4%. Gastrointestinal symptoms were the most common complaint, present in 86.5%, followed by fatigue in 29%, weight loss in 20.5%, anemia in 17.1% and dermatitis herpetiformis in 5.2%. The median time of follow up for these patients was 3.1 years (range 0.1-17). As previously described, inadvertent gluten exposure was the most common cause, however over 15 different etiologies were identified. (Figure 1) Table 2 shows characteristics of our NRCD cohort compared to patients responsive to the GFD. Of these characteristics, the duration of the GFD, being referred from another institution and the presence of depression or anxiety were each found to be significantly associated with NRCD (p < 0.005 for each). Conclusion NRCD is a common problem and although gluten ingestion is the most common cause there are a multitude other causes. A shorter duration of GFD adherence is an important factor probably reflecting lack of experience with the diet. NRCD is a common reason for referral to a specialized celiac center. Depression and anxiety should be diagnosed and treated in nonresponsive patients as they are possible contributors to symptoms. Given the frequency which with NRCD occurs and the breadth of etiologies it is important for clinicians to follow the diagnostic algorithms that have been developed to efficiently identify specific etiologies for their patients to guide their management. Table 1
Table. Gluten consumption as measured in feces.
Medians are compared with Wilcoxon rank-sum test and frequencies with Chi-square test. *Two patients were diagnosed with small-intestinal lymphoma on initial evaluation. **Data was available for 270 nonresponsive and 407 responsive patients.
AGA Abstracts
S-480
Su1138 GENDER-BASED DIFFERENCES IN UNDIAGNOSED CELIAC DISEASE: SUBTLER THAN IMAGINED Claire Jansson-Knodell, RokSon Choung, Katherine S. King, Joseph J. Larson, Carol T. Van Dyke, Tricia Brantner, Alberto Rubio-Tapia, Joseph A. Murray
Figure 1 Since more than one diagnosis was made in some patients the total number of etiologies adds up to more than 100%. *Includes type 1 and type 2 refractory CD, ulcerative jejunitis and small intestinal lymphoma. **Includes eosinophilic esophagitis (3), drugs side effects (3), duodenal adenocarcinoma (2), cirrhosis complications (2), esophageal motility disorders (1), post-surgical adhesions (1), dumping syndrome (1), common variable immunodeficiency (1), rectal prolapse (1), fibromyalgia (1), microsporidiasis (1), pyloric stenosis(1) and a post-partum flair (1).
INTRODUCTION: The impact of undiagnosed celiac disease on women's health is unclear. There is a paucity of research focused on gender-based differences in undiagnosed populations with celiac disease. The objective of this study was to estimate gender-based differences in a community-based cohort of patients seropositive for celiac disease with respect to 1) age, 2) anthropomorphic measurements, and 3) associated autoimmune diseases. METHODS: Stored serum from a community-based sample of 30,425 people, aged 18-49 years old residing in a Minnesota county was tested for celiac disease using tissue transglutaminase (TTG) and endomysial antibody (EMA) between 2006 and 2011. Clinical data were systematically abstracted from the electronic medical record of patients who were seropositive for celiac disease defined as both TTG-IgA and EMA positive testing. Categorical data were analyzed with Chi-square and Fisher's exact test. Age was studied with the equal variance T-test. RESULTS: In this community-based cohort, 338 (1.1%) subjects were identified with undiagnosed celiac disease or celiac disease autoimmunity. That group was comprised of 213 females (prevalence 1.2%) and 125 males (prevalence 0.98%) (p=0.07). A representative sample of those with celiac disease autoimmunity showed that seropositive women were younger with an average age of 33.8 years compared to 37.4 years in their male counterparts (p=0.002); the average age of individuals tested was 34.9 years in women and 36.4 years in men. Women in the seropositive group had a lower average body mass index (BMI) of 26.2 versus 28.1 in men (p=0.028) as seen in the baseline characteristics table. Concurrent autoimmune diseases were recorded in 36 of the females and 25 of the males (females 20.6%; males 24.8%; p=0.42). Depression was more common in seropositive females than males (females 27.7%; males 9.8%, p=0.0004). DISCUSSION: Celiac disease is common. The finding of frequent seropositive individuals emphasizes the importance of awareness of undiagnosed celiac disease. These data indicate the potential of gender-based differences in terms of age at detection, anthropometric measurements where >50% are overweight or obese, and associated diseases that can co-occur with celiac disease. Surprisingly, males with celiac disease autoimmunity were just as likely as females to have an autoimmune disease. These results may have clinical implications for uncovering cases of celiac disease and once identified, managing them comprehensively. Sample of Undiagnosed Celiac Cases
Su1136 NO DETRIMENTAL EFFECT OF OATS ON SYMPTOMS, HISTOLOGICAL PARAMETERS, SEROLOGICAL TESTS, OR QUALITY OF LIFE IN CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS María Inés Pinto Sanchez, Natalia Causada Calo, Alexander C. Ford, Joseph A. Murray, Premysl Bercik, Paul Moayyedi, Elena F. Verdu, Peter H. R. Green Background: Current management of celiac disease (CD) is a life-long gluten free diet (GFD) that excludes wheat, rye, and barley. Oats may increase the nutritional value of a GFD, but their use remains controversial due to reports on oat intolerance in some patients. Objectives: To perform a systematic review and meta-analysis to assess the evidence on safety of oat consumption as a part of a GFD for patients with CD and DH. Selection criteria: We included clinical trials and observational studies evaluating the effect of oats within a GFD on symptoms, serological, and histological responses in patients with CD, using electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), and SIGLE. Two authors collected the data independently. GRADE approach was used for quality of the body of evidence. Results: 422 studies were identified and 32 were eligible for analysis. 16/32 papers were clinical trials, 6 randomized control trials (RCT; 3 in children, 3 in adults), 2 non-RCTs and 8 post hoc reports from RCTs. A meta-analysis was performed in 6 RCTs; none evaluated DH. All RCTs involved pure/uncontaminated oats. There was no difference in gastrointestinal symptoms in adult CD patients treated with GFD with or without oats for 12 months (standardized mean difference (SMD) -0.22; 95% confidence interval (CI) -0.56 to 0.13; P=0.22). The quality of evidence was very low. 16 studies (5 RCTs) evaluated the histological response to oats in patients with CD for 12 months, and no differences in histological indices were observed between groups (SMD: -0.0; 95% CI -0.01 to 0.01; P=0.92). Similar proportions of patients in both groups had histological remission after treatment (relative risk (RR) 0.24; 95% CI 0.01-4.8; P=0.35). The quality of evidence was low. Based on low to moderate quality evidence, there was no difference in intraepithelial lymphocyte counts in patients on a GFD with and without oats (SMD: 0.21; 95% CI -1.44 to 1.86). Subgroup analysis on adult patients vs. children did not reveal any differences. There was no difference in serological response measured by tTG (RR 1.71; 95% CI 0.62-4.71; P=0.89); EmA (RR 1.45; 95% CI 0.77-2.74; P=0.25) or antigliadin antibodies in patients on a GFD with or without oats. The studies in adults were of lower quality. No difference in quality of life was observed between patients consuming or not consuming oats (SMD-2.5; 95%CI -13.86 to 8.86; P=0.67). The quality of evidence was very low. Conclusions: We could not find evidence that oats have detrimental effects on the key outcomes assessed in this study in patients with CD on a GFD. However, there were few studies for many of the endpoints, and the quality of evidence was low. Rigorous double-blind placebo-controlled RCTs are needed to evaluate the effect of oat consumption as part of a GFD in patients with CD.
Su1137 ASPERGILLUS NIGER-DERIVED ENZYME DEGRADES GLUTEN IN THE STOMACH OF GLUTEN-SENSITIVE SUBJECTS Julia König, Savanne Holster, Maaike J Bruins, Robert J. Brummer Rationale: Gluten may cause gastrointestinal complaints in individuals sensitive to gluten. Aspergillus niger-derived prolyl endoprotease (AN-PEP) has previously been shown to degrade gluten into non-immunogenic compounds in an in vivo setting in healthy subjects in which AN-PEP was added to a liquid, intragastrically infused meal1. The current study investigated the efficacy of AN-PEP to degrade gluten in a physiological meal setting in gluten-sensitive subjects. Methods: In this randomized placebo-controlled cross-over study, 18 self-reported gluten-sensitive subjects attended three test days. A multilumen nasoduodenal feeding catheter was placed to collect gastric and duodenal aspirates. Subjects consumed a porridge containing approximately 0.5 g gluten in the form of two crumbled wheat cookies as well as two tablets either containing 160 000 PPI of AN-PEP (high dose), or 80 000 PPI (low dose), or placebo in a double-blinded, randomized manner. Gastric and duodenal content was sampled at several time points over 180 minutes and analysed for gluten epitopes using the Gluten-Tec® ELISA. The 180-min areas under the curve (AUC) of epitope concentration were calculated using curve fitting. Additionally, participants were asked to fill in questionnaires (GSRS) after each test day. The non-parametric Wilcoxon signed-ranked paired test at α=0.05 with a Bonferroni correction was used to detect significant differences. Results: AN-PEP significantly lowered the gluten concentrations in the stomach and in the duodenum
S-481
AGA Abstracts
AGA Abstracts
compared to the placebo in both the high dose and the low dose. In the stomach, gluten levels were reduced from 218 ± 155 µgxmin/ml (mean ± STD) in the placebo to 31 ± 24 µgxmin/ml in the high dose (p=0.001) and to 31 ± 22 µgxmin/ml in the low dose (p=0.001). In the duodenum, gluten levels were reduced from 65 ± 88 µgxmin/ml in the placebo to 12 ± 13 µgxmin/ml in the high dose (p=0.019) and to 8 ± 5 µgxmin/ml in the low dose (p=0.015). Conclusions: Even in a physiological meal setting, AN-PEP significantly degraded most gluten before it entered the duodenum in self-reported gluten-sensitive subjects. In those subjects, the consumption of AN-PEP was well tolerated. 1) Salden et al. Aliment Pharmacol Ther 2015; 42:273-285.