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Histologic Findings in Gastric Biopsies at Diagnosis and Follow-Up in an Adult Celiac Disease Population
AGA Abstracts
PPV of the tTG for BxCeD according to the presence of other comorbidities
Dis +: either liver, auto-immune, infectious or inflammatory disease at the time of tTG
Sa1284
Sa1286
HISTOLOGIC FINDINGS IN GASTRIC BIOPSIES AT DIAGNOSIS AND FOLLOW-UP IN AN ADULT CELIAC DISEASE POPULATION Amelie Therrien, Gabriel Bernard, Pierre-Olivier Hetu, Mickael Bouin
DO WE PROPERLY DIAGNOSE OUR CELIAC PATIENTS? THREE YEAR FOLLOW UP IN A CELIAC REFERRAL CENTER Aria Zand, Natalie E. Duran, Eric Esrailian, Daniel Hommes, Guy A. Weiss
BACKGROUND: Chronic gastritis (CG) and lymphocytic gastritis (LG) have been described in pediatric populations with celiac disease (CeD). A U.S. national review of gastric and duodenal biopsies showed an association between duodenal histology compatible with CeD and the presence of CG or LG. However, this transversal study did not include clinical or serological data. AIM: To evaluate, in an adult CeD cohort, the gastric histologic findings at diagnosis of CeD and at follow-up on a gluten free diet (GFD). METHOD: Longitudinal chart review study at Centre Hospitalier de l'Université de Montréal (Montreal, Canada) from August 2003 to June 2016. Were included every new cases of CeD (presence of tissue transglutaminase antibodies (tTG) and a duodenal biopsy with criteria for Marsh 1 to 3c classification, without any notion of previous GFD). Medical record, endoscopic and pathology reports were reviewed. Mann-Whitney U and Fisher tests were used to compare continuous and categorical variables respectively. RESULTS: 186 cases of CeD were diagnosed (47.3 years SD 15.9; 64.0% of female). Concomitant gastric biopsies were done in 43% of them (n=80). Gastroscopy findings were abnormal in 34% (n=27), the main endoscopic finding being gastric mucosal erythema (n=18). Gastric histology was abnormal in 64% (n= 51); inactive CG (n=27), active CG without helicobacter pylori (Hp) (n=7), Hp infection (n=5), reactional gastropathy (n=4), gastric polyps (n=2), LG (n=3), parietal cells pseudohypertrophy (n=2) and intestinal metaplasia (n=1). No differences were found between the level of increase of tTG in the subgroup with abnormal gastric histologic findings (his+) and the subgroup with normal findings (his-), as for the proportion of patients with moderate to severe duodenal villous atrophy. Among patients with his+, 59% had a normal gastric endoscopic appearance, compared to 79% in the group with his-(p=0,09). No differences were neither found between the proportion of his+ and his- patients with GI symptomatology or anemia. 22% of patients with his+ and 24% with his- were both asymptomatic with normal endoscopy. So far, 10 individuals had subsequent gastric biopsies after self-reported GFD, on average 38.2 months (95% CI 20.6 to 55.8 months) after initial biopsy. Of these, three remained normal and six patients with initial abnormal histologic findings showed either normal histology (n = 5) or improvement (inactive CG vs active CG, n = 1). The only case without improvement had recurrent Hp infection. CONCLUSION: Although gastric histologic findings at diagnosis in an adult population with celiac disease are manifold, CG is the more frequent abnormality. No association was found with the severity of celiac disease. Gastritis seems to improve at follow-up.
Introduction Celiac disease (CD) is a chronic autoimmune condition caused by intestinal inflammation triggered by gluten exposure. The clinical, ancillary, and histopathological findings are variable, often leading to a diagnostic challenge. The prevalence of CD in the US is approximately 1% and most patients remain undiagnosed. The 2013 ACG guidelines recommend one or two bulbar biopsies and at least four biopsies of the distal duodenum. We, therefore, aimed to assess the adherence to these guidelines in our suspected celiac population. Methods We retrospectively analyzed the electronic records of all adult subjects with tested celiac serology or prior outside diagnosis of CD, who underwent an upper endoscopy between the years 2014-2016 at the UCLA Celiac Program by faculty physicians. Chart review included patient demographics (age, race, ethnicity) as well as endoscopy and pathology results of the biopsies taken. We documented whether biopsies were obtained in accordance with the 2013 ACG guidelines. Results Ninety-three subjects with serologic and endoscopic testing were identified in the past 3 years, of whom 27 patients were excluded because of negative serology and/or upper endoscopy for another indication, leaving 66 patients that were included. The mean age at presentation was 43.7 (SD±16.8) years, 74.2% of them were female, 84.9% classified as white or Caucasian racially out of which 94% reported a not Hispanic or Latino ethnicity. Interestingly, about 40% of the 66 patients were diagnosed with CD despite poor adherence to current endoscopic guidelines. Conclusions Only 60% of our study cohort were diagnosed with CD in accordance with the guidelines. Although in the remainder 40% the inappropriate biopsies were sufficient, this raises a concern for under-diagnosis of CD and warrants an educational intervention for gastroenterologists regarding the 2013 ACG guidelines.
Sa1287 ROLE OF HLA TYPING IN PATIENTS WITH WEAKLY POSITIVE TISSUE TRANSGLUTAMINASE IGA Ayush Sharma, Rok Seon Choung, Melissa Snyder, Joseph A. Murray Background and aims: Celiac disease (CD) is an immune mediated chronic inflammatory disease that is associated with HLA-DQ2 and DQ8 alleles. Genetic screening for CD has limited clinical utility and is generally used to exclude the diagnosis in patients not carrying either the DQ2 or DQ8 haplotype. CD is generally diagnosed based on positive serology, most often tissue transglutaminase IgA (tTG IgA). However, the clinical significance of a weakly positive tTG IgA may be unclear. The goal of this study was to assess the distribution of HLA alleles in patients with weak and strong tTG IgA positive patients and to characterize the correlation of HLA alleles and endomysial antibodies (EMA) or deaminated gliadin IgA antibodies in patients with weakly positive tTG IgA. Methods: Samples with positive tTG IgA (n=436) and weakly positive tTG IgA (n=196) were collected from patients for whom routine celiac serology and HLA typing had been ordered. Patients with weakly positive tTG IgA results were also tested for deamidated gliadin IgA and endomysial IgA (EMA). HLA-DQ alleles were stratified into 5 groups: DQ2 homozygous, DQ2 heterozygous, DQ2/ DQ8, DQ8 hetero or homozygous and absence of DQ2 or DQ 8 (non-permissive). Results: Patients with positive tTG IgA had a higher prevalence of DQ homozygosity (35.5%) compared to patients with weakly positive tTG IgA (20.4%) (Table I). In contrast, patient with weakly positive tTG IgA were more likely to be negative for both DQ2 and DQ8 (8.2%) compared to the tTG IgA positive group (1.0%). The distribution of DQ2 heterozygous, DQ2/DQ8 and DQ8 hetero/homozygous was very similar for both the groups. Of the patients with weakly positive tTG IgA results who were DQ2 homozygous (n=40), 77.5% were positive for deamidated gliadin IgA and/or EMA. In contrast, in individuals with nonpermissive HLA alleles (n=16), the weakly positive tTG IgA correlated with a positive deamidated gliadin IgA and/or EMA in only 2 patients (12.5%). In the other HLA groups, a positive deamidated gliadin IgA and/or EMA occurred in 60% of DQ2 heterozygotes, 70% of DQ2/DQ8 heterozygotes, and 46.7% of DQ8 heterozygotes/homozygotes with weakly positive tTG IgA results (Table II). Conclusion: Patients with weakly positive tTg IgA have a higher probability of having non-permissive celiac genes than patients with positive serology. In patients with weakly positive tTG IgA, HLA types with DQ2 homozygous and DQ2/DQ8 are more likely to have a positive serology for EMA or deamidated gliadin IgA than in patients with DQ2 heterozygous and DQ8 hetero or homozygous. In tTG IgA positive it is rare for those patients not to have permissive HLA genes (1%). These results suggest that HLA typing could be a useful tool in further evaluation of patients with weakly positive tTG IgA serology.
Sa1285 NON-INVASIVE BIOMARKERS FOR ASSESSMENT OF VILLOUS ABNORMALITIES IN PATIENTS WITH CELIAC DISEASE AND OTHER ENTEROPATHIES: AN ALTERNATIVE TO MUCOSAL BIOPSIES Alka Singh, Anil Verma, Prasenjit Das, Gaurav Jindal, Shyam Prakash, Baibaswata Nayak, Siddhartha Datta Gupta, Lalit Kumar, Vineet Ahuja, Govind K. Makharia Introduction: While villous atrophy is the hallmark of celiac disease (CeD), it however requires endoscopy which is an invasive procedure. There is a need of non-invasive biomarker both for diagnosis and monitoring of CeD. Patients and methods: Levels of citrulline (synthetic marker for enteropathy) and intestinal fatty acid binding protein (I-FABP) (marker for enterocytic injury) in plasma and regenerating gene 1α (Reg1α) (marker of enterocyte regeneration) in serum were estimated in treatment naïve patients with CeD (n=110), other enteropathies (n=46), healthy controls (n=209) and disease controls (n=103). The expression of I-FABP and Reg1α were also done in duodenal biopsies using immunohistochemistry and quantitative PCR. In order to validate citrulline synthesis in the intestinal mucosa, the expression of pyrolline-5-carboxylate synthase (P5CS), a rate limiting enzyme in citrulline synthesis, was performed in duodenal biopsy by immunohistochemistry. Forty three patients with CeD and 18 with other enteropathies were re-evaluated following six months of gluten free diet (GFD) and specific treatment of specific enteropathy, respectively. To further confirm utility of above markers, a human model was selected having cycles of enterocyte injury and recovery such as patients with haematological malignancies receiving high-dose chemotherapy for HSCTs (n=70) and their samples were obtained at various time points both before and after HSCT. Results: Citrulline levels in plasma as well as expression of P5CS in tissue were significantly lower in treatment naïve CeD as compared to controls (p<0.001), levels increased significantly after GFD. While plasma I-FABP level was significantly higher, the tissue expression of I-FABP was lower in treatment naïve CeD as compared to controls (p<0.001). Plasma I-FABP level decreased and tissue expression of I-FABP increased after GFD. Reg1α level in serum and in tissue were higher in treatment naïve CeD which decreased after 6 months of GFD (p<0.003). In a human model of enteropathy, sequential decrease and then increase in citrulline levels occurred, following a pattern of enterocyte injury and recovery, which corresponded to total leucocytes count in peripheral blood (Fig). Conclusions: The consistent changes in the level of plasma citrulline in all above experimental groups along with changes in expression pattern of P5CS (supporting marker of citrulline) suggest that plasma citrulline is a reliable marker of enteropathy both for diagnosis and monitoring of villous atrophy.
AGA Abstracts
S-264
PPV of the tTG for BxCeD according to the presence of other comorbidities
Dis +: either liver, auto-immune, infectious or inflammatory disease at the time of tTG
Sa1284
Sa1286
HISTOLOGIC FINDINGS IN GASTRIC BIOPSIES AT DIAGNOSIS AND FOLLOW-UP IN AN ADULT CELIAC DISEASE POPULATION Amelie Therrien, Gabriel Bernard, Pierre-Olivier Hetu, Mickael Bouin
DO WE PROPERLY DIAGNOSE OUR CELIAC PATIENTS? THREE YEAR FOLLOW UP IN A CELIAC REFERRAL CENTER Aria Zand, Natalie E. Duran, Eric Esrailian, Daniel Hommes, Guy A. Weiss
BACKGROUND: Chronic gastritis (CG) and lymphocytic gastritis (LG) have been described in pediatric populations with celiac disease (CeD). A U.S. national review of gastric and duodenal biopsies showed an association between duodenal histology compatible with CeD and the presence of CG or LG. However, this transversal study did not include clinical or serological data. AIM: To evaluate, in an adult CeD cohort, the gastric histologic findings at diagnosis of CeD and at follow-up on a gluten free diet (GFD). METHOD: Longitudinal chart review study at Centre Hospitalier de l'Université de Montréal (Montreal, Canada) from August 2003 to June 2016. Were included every new cases of CeD (presence of tissue transglutaminase antibodies (tTG) and a duodenal biopsy with criteria for Marsh 1 to 3c classification, without any notion of previous GFD). Medical record, endoscopic and pathology reports were reviewed. Mann-Whitney U and Fisher tests were used to compare continuous and categorical variables respectively. RESULTS: 186 cases of CeD were diagnosed (47.3 years SD 15.9; 64.0% of female). Concomitant gastric biopsies were done in 43% of them (n=80). Gastroscopy findings were abnormal in 34% (n=27), the main endoscopic finding being gastric mucosal erythema (n=18). Gastric histology was abnormal in 64% (n= 51); inactive CG (n=27), active CG without helicobacter pylori (Hp) (n=7), Hp infection (n=5), reactional gastropathy (n=4), gastric polyps (n=2), LG (n=3), parietal cells pseudohypertrophy (n=2) and intestinal metaplasia (n=1). No differences were found between the level of increase of tTG in the subgroup with abnormal gastric histologic findings (his+) and the subgroup with normal findings (his-), as for the proportion of patients with moderate to severe duodenal villous atrophy. Among patients with his+, 59% had a normal gastric endoscopic appearance, compared to 79% in the group with his-(p=0,09). No differences were neither found between the proportion of his+ and his- patients with GI symptomatology or anemia. 22% of patients with his+ and 24% with his- were both asymptomatic with normal endoscopy. So far, 10 individuals had subsequent gastric biopsies after self-reported GFD, on average 38.2 months (95% CI 20.6 to 55.8 months) after initial biopsy. Of these, three remained normal and six patients with initial abnormal histologic findings showed either normal histology (n = 5) or improvement (inactive CG vs active CG, n = 1). The only case without improvement had recurrent Hp infection. CONCLUSION: Although gastric histologic findings at diagnosis in an adult population with celiac disease are manifold, CG is the more frequent abnormality. No association was found with the severity of celiac disease. Gastritis seems to improve at follow-up.
Introduction Celiac disease (CD) is a chronic autoimmune condition caused by intestinal inflammation triggered by gluten exposure. The clinical, ancillary, and histopathological findings are variable, often leading to a diagnostic challenge. The prevalence of CD in the US is approximately 1% and most patients remain undiagnosed. The 2013 ACG guidelines recommend one or two bulbar biopsies and at least four biopsies of the distal duodenum. We, therefore, aimed to assess the adherence to these guidelines in our suspected celiac population. Methods We retrospectively analyzed the electronic records of all adult subjects with tested celiac serology or prior outside diagnosis of CD, who underwent an upper endoscopy between the years 2014-2016 at the UCLA Celiac Program by faculty physicians. Chart review included patient demographics (age, race, ethnicity) as well as endoscopy and pathology results of the biopsies taken. We documented whether biopsies were obtained in accordance with the 2013 ACG guidelines. Results Ninety-three subjects with serologic and endoscopic testing were identified in the past 3 years, of whom 27 patients were excluded because of negative serology and/or upper endoscopy for another indication, leaving 66 patients that were included. The mean age at presentation was 43.7 (SD±16.8) years, 74.2% of them were female, 84.9% classified as white or Caucasian racially out of which 94% reported a not Hispanic or Latino ethnicity. Interestingly, about 40% of the 66 patients were diagnosed with CD despite poor adherence to current endoscopic guidelines. Conclusions Only 60% of our study cohort were diagnosed with CD in accordance with the guidelines. Although in the remainder 40% the inappropriate biopsies were sufficient, this raises a concern for under-diagnosis of CD and warrants an educational intervention for gastroenterologists regarding the 2013 ACG guidelines.
Sa1287 ROLE OF HLA TYPING IN PATIENTS WITH WEAKLY POSITIVE TISSUE TRANSGLUTAMINASE IGA Ayush Sharma, Rok Seon Choung, Melissa Snyder, Joseph A. Murray Background and aims: Celiac disease (CD) is an immune mediated chronic inflammatory disease that is associated with HLA-DQ2 and DQ8 alleles. Genetic screening for CD has limited clinical utility and is generally used to exclude the diagnosis in patients not carrying either the DQ2 or DQ8 haplotype. CD is generally diagnosed based on positive serology, most often tissue transglutaminase IgA (tTG IgA). However, the clinical significance of a weakly positive tTG IgA may be unclear. The goal of this study was to assess the distribution of HLA alleles in patients with weak and strong tTG IgA positive patients and to characterize the correlation of HLA alleles and endomysial antibodies (EMA) or deaminated gliadin IgA antibodies in patients with weakly positive tTG IgA. Methods: Samples with positive tTG IgA (n=436) and weakly positive tTG IgA (n=196) were collected from patients for whom routine celiac serology and HLA typing had been ordered. Patients with weakly positive tTG IgA results were also tested for deamidated gliadin IgA and endomysial IgA (EMA). HLA-DQ alleles were stratified into 5 groups: DQ2 homozygous, DQ2 heterozygous, DQ2/ DQ8, DQ8 hetero or homozygous and absence of DQ2 or DQ 8 (non-permissive). Results: Patients with positive tTG IgA had a higher prevalence of DQ homozygosity (35.5%) compared to patients with weakly positive tTG IgA (20.4%) (Table I). In contrast, patient with weakly positive tTG IgA were more likely to be negative for both DQ2 and DQ8 (8.2%) compared to the tTG IgA positive group (1.0%). The distribution of DQ2 heterozygous, DQ2/DQ8 and DQ8 hetero/homozygous was very similar for both the groups. Of the patients with weakly positive tTG IgA results who were DQ2 homozygous (n=40), 77.5% were positive for deamidated gliadin IgA and/or EMA. In contrast, in individuals with nonpermissive HLA alleles (n=16), the weakly positive tTG IgA correlated with a positive deamidated gliadin IgA and/or EMA in only 2 patients (12.5%). In the other HLA groups, a positive deamidated gliadin IgA and/or EMA occurred in 60% of DQ2 heterozygotes, 70% of DQ2/DQ8 heterozygotes, and 46.7% of DQ8 heterozygotes/homozygotes with weakly positive tTG IgA results (Table II). Conclusion: Patients with weakly positive tTg IgA have a higher probability of having non-permissive celiac genes than patients with positive serology. In patients with weakly positive tTG IgA, HLA types with DQ2 homozygous and DQ2/DQ8 are more likely to have a positive serology for EMA or deamidated gliadin IgA than in patients with DQ2 heterozygous and DQ8 hetero or homozygous. In tTG IgA positive it is rare for those patients not to have permissive HLA genes (1%). These results suggest that HLA typing could be a useful tool in further evaluation of patients with weakly positive tTG IgA serology.
Sa1285 NON-INVASIVE BIOMARKERS FOR ASSESSMENT OF VILLOUS ABNORMALITIES IN PATIENTS WITH CELIAC DISEASE AND OTHER ENTEROPATHIES: AN ALTERNATIVE TO MUCOSAL BIOPSIES Alka Singh, Anil Verma, Prasenjit Das, Gaurav Jindal, Shyam Prakash, Baibaswata Nayak, Siddhartha Datta Gupta, Lalit Kumar, Vineet Ahuja, Govind K. Makharia Introduction: While villous atrophy is the hallmark of celiac disease (CeD), it however requires endoscopy which is an invasive procedure. There is a need of non-invasive biomarker both for diagnosis and monitoring of CeD. Patients and methods: Levels of citrulline (synthetic marker for enteropathy) and intestinal fatty acid binding protein (I-FABP) (marker for enterocytic injury) in plasma and regenerating gene 1α (Reg1α) (marker of enterocyte regeneration) in serum were estimated in treatment naïve patients with CeD (n=110), other enteropathies (n=46), healthy controls (n=209) and disease controls (n=103). The expression of I-FABP and Reg1α were also done in duodenal biopsies using immunohistochemistry and quantitative PCR. In order to validate citrulline synthesis in the intestinal mucosa, the expression of pyrolline-5-carboxylate synthase (P5CS), a rate limiting enzyme in citrulline synthesis, was performed in duodenal biopsy by immunohistochemistry. Forty three patients with CeD and 18 with other enteropathies were re-evaluated following six months of gluten free diet (GFD) and specific treatment of specific enteropathy, respectively. To further confirm utility of above markers, a human model was selected having cycles of enterocyte injury and recovery such as patients with haematological malignancies receiving high-dose chemotherapy for HSCTs (n=70) and their samples were obtained at various time points both before and after HSCT. Results: Citrulline levels in plasma as well as expression of P5CS in tissue were significantly lower in treatment naïve CeD as compared to controls (p<0.001), levels increased significantly after GFD. While plasma I-FABP level was significantly higher, the tissue expression of I-FABP was lower in treatment naïve CeD as compared to controls (p<0.001). Plasma I-FABP level decreased and tissue expression of I-FABP increased after GFD. Reg1α level in serum and in tissue were higher in treatment naïve CeD which decreased after 6 months of GFD (p<0.003). In a human model of enteropathy, sequential decrease and then increase in citrulline levels occurred, following a pattern of enterocyte injury and recovery, which corresponded to total leucocytes count in peripheral blood (Fig). Conclusions: The consistent changes in the level of plasma citrulline in all above experimental groups along with changes in expression pattern of P5CS (supporting marker of citrulline) suggest that plasma citrulline is a reliable marker of enteropathy both for diagnosis and monitoring of villous atrophy.
AGA Abstracts
S-264