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W1036 Do Tissue Transglutaminase Antibodies in Celiac Disease Contribute to Thyroid Autoimmunity?
AGA Abstracts
patients (44.4%) had a divergent diagnosis (23 patients originally identified as CD and 1 diagnosed as non CD) (Cohen's kappa statistic for the overall agreement: 0.19). Misdiagnosis was mainly produced by an over diagnosis of CD (53.5% vs. 9.1%; OR: 11.5, 95% CI 1.3597.9; p<0.02). Compared with the gold standard serology, 39 patients (72.2%) had congruent results in practice (Cohen's kappa: 0.45) On the other hand, compared with the gold standard histological review, 28 samples (51.8%) had congruent diagnoses by the external pathologists (Cohen's kappa: 0.14). Misinterpretation was mainly due to a wrong diagnosis of enteropathy in non CD cases (OR: 30.0; 95% CI 5.7-157.7; p<0.0001). Conclusions: Our study detected a high rate of serological and histopathological misdiagnosis of CD in clinical practice. This was mainly due to a histologic overdiagnosis of CD. Although the nature of consultations in our referral center suggests a potential overestimation of the true prevalence of the problem, pitfalls in clinical practice may have profound negative impact on patients.
W1038 From Intra- to Extra-Gastric Role of Helicobacter pylori: Implications On Metabolic Syndromes Mohammad Khaled Helicobacter pylori (H. pylori) is well known for its association with many gastric ailments, particularly gastric ulcers leading to gastric cancer. Controversial reports exist in the literature on the association of H. pylori with coronary heart disease (CHD). This bacterium is highly prevalent in Bangladeshi populations in concomitant with the prevalence of CHD. This prompted us to investigate any possible role of H. pylori in the initiation and/or aggravation cardiovascular diseases. Using a cross-sectional analytic (case-control) design, 72 subjects were recruited who underwent coronary angiography to diagnose CHD. Based on the arterial narrowing of ≥ 50%, 40 (55%) of these subjects were diagnosed with CHD, while 32 (44%) were found to be normal. Demographic data, history, findings of physical examinations were recorded. Levels of fasting serum glucose, TG, HDL, TC were measured by the enzymatic photometry, while insulin, anti-H. pylori IgG antibody, CRP and thromboxane (TXB) were measured by enzyme immunoassay. The insulin resistance and insulin secretory defect were estimated using HOMA-CIGMA software. H. pylori cytotoxin-associated (cagA) and vacuolization cytotoxin (vacA) were detected by Western blot analysis. A total of 26 (65%) CHD patients (cases) and 16 (50%) normal (control) subjects were seropositive for H. pylori infection. Logistic regression analyses revealed that H. pylori (vacA) (β= -1.896, p=0.049) and insulin secretory defect (β= 6.911, p=0.013) are independent predictors of CHD. H. pylori (vacA) was also significantly associated with higher levels of fasting glucose (p=0.047), insulin resistance (p=0.044), CRP (p=0.05) and TXB (p=0.049). These findings suggest, for the first time to our knowledge, that the extragastric pathogenicity of H. pylori (vacA) may be mediated by influencing the metabolic syndromes, like insulin resistance and CRP, and by affecting insulin secretion from the pancreatic β-cells, as found in this study.
W1036 Do Tissue Transglutaminase Antibodies in Celiac Disease Contribute to Thyroid Autoimmunity? Afzal J. Naiyer, Jayesh Shah, Jianfeng Cheng, Lincoln Hernandez, Edward J. Ciaccio, John S. Manavalan, Govind Bhagat, Peter H. Green Aim: Celiac disease is associated with autoimmune thyroid disorders. Thyroid dysfunction in patients with active celiac disease (ACD) improves on institution of gluten-free diet (GFD). We thus determined whether tissue transglutaminase-2 IgA antibodies (anti-TG2) have a role in the development of thyroid autoimmunity. Methods: Serum from 40 ACD patients, prior to commencing a gluten-free diet, 46 patients on a GFD, 40 healthy (NC) and 25 disease control (DC) subjects were used. All sera were screened for anti thyroperoxidase (ATPO) and thyroglobulin (ATG) antibodies, thyroid stimulating harmone (TSH) and freeT4 (FT4) levels. Indirect immunofluorescence (IIF) was performed on primate thyroid tissue sections using anti-thyroid seronegative sera. Results: IIF with thyroid seronegative, antiTG2 positive ACD sera (n=21) demonstrated staining of thyroid follicular cells as well as extracellular matrix in the interfollicular areas. The IIF patterns of monoclonal anti-human TG2 antibody and patient sera with anti-TG2 were superimposeable. Evidence of TG2 as the antigen was supported by complete abrogation of the IIF pattern when patient sera was depleted of anti-TG2 by pretreatment with human recombinant TG2 or recombinant TG2 bound beads. No staining was observed with sera from patients on GFD and negative antiTG2 or in normal and disease controls. In order to observe the clinical significance of the binding of anti-TG2 to thyroid tissue we assessed thyroid autoimmunity in the study population. Thyroid antibodies were found in 43% ACD patients, significantly higher than NC and DC (p<0.0001). There was a positive correlation between the anti-TG2 and ATPO titers (p=0.0001; r=0.63). Furthermore the mean age of ACD patients was significantly higher in the presence of ATPO antibodies than in its absence (50.3 ± 3.1 vs 36.3 ± 3.7, = 0.01). Overall there was no age difference between active celiac disease, GFD and healthy controls with the exception of the disease control group which was significantly older than the ACD group (50.2 ± 3.3 vs 41.7 ± 2.4, p =0.03). Thyroid dysfunction was identified in 8 ACD patients, 4 had a past medical history of autoimmune thyroid disease with the other 4 with no prior thyroid disease. Conclusions: Thyroid disease is common in celiac patients. Anti-TG2 antibodies in untreated celiac disease bind to TG2 in thyroid tissue. A positive correlation exists between of anti-TG2 and ATPO titers in active celiac patients. Our data suggests that anti-TG2 may play a role in the development of thyroid autoimmunity in celiac disease. This may be may be more important in older celiac disease patients.
W1039 Helicobacter pylori Infection and Impaired Drug Absorption: A Systematic Review Edith Lahner, bruno annibale, Gianfranco Delle Fave Background & Aim: Drug absorption influences the efficacy of orally administered therapy and gastric secretion may affect drug absorption. Impaired gastric acid secretion is a common consequence of H pylori-induced gastritis, mainly in corpus. Thus, H pylori-induced gastritis may potentially affect the absorption of orally administered drugs. This review is aimed to focuse on the evidence of impaired drug absorption associated with H pylori infection. Data Sources: Systematic search of MEDLINE/ EMBASE databases (1980-September 2007) for English-language articles using the keywords drug malabsorption and absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study Selection: From 2,099 retrieved articles, 5 studies were identified (1 randomized controlled trial, 2 controlled crossover studies, 1 case-control study, and 1 case series) showing a significant variation in study population and design and type of intervention. Data Extraction: From each selected paper, information on the investigated drug, type of the study, main features of investigated subjects, study design, type of intervention, and study results were extracted. Results: 5 studies investigated the absorption of drugs (three) in association with H pylori infection: L-dopa, thyroxine, and delavirdine. H pylori infection was assessed by serology in 3 studies and also by histology in 2 studies. In 4 studies drug absorption was investigated with respect to eradication treatment and in 2 studies with respect to gastric acidity. Impaired absorption was reported in association with H pylori infection. (Table). Conclusions: A plausible mechanism of impaired drug absorption is the reduced gastric acid secretion in pts with H pylori gastritis. The H pylori infection and the associated hypochlorhydria, should be considered in prescribing drugs whose absorption is potentially affected by the intragastric pH.
W1037 Collagenous Colitis: Clinical Presentation, Treatment and Outcome of 287 Patients Ahmed Madisch, Stephan Miehlke, Franziska Bartosch, Birgit Bethke, Manfred Stolte Background: Collagenous colitis is a chronic disorder characterized by watery diarrhea. Clinical features or treatment outcomes in a large group of patients are sparse and only retrospectively collected. Aim: to evaluate prospectively the clinical features, response to treatment and outcomes in a large group of patients with collagenous colitis. Patients and Methods: Patients with histologically confirmed collagenous colitis were prospectively enrolled to complete a questionnaire on onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment success and concomitant diseases. Results: A total of 286 patients (female n=220 (76,9%); mean age 65,81 years, range 35-92 years) were available for analysis. Prior to diagnosis the mean duration of symptoms was 37,1 months (range 2 days to 30,41 years). At diagnosis the daily mean stool frequency was 6,88 (range 1-42). Abdominal pain were reported by 99 patients (34,6%), weight loss (mean 3,23 kg) by 140 patients (49%) and nocturnal stools by 185 patients (64,7%). Concomitant autoimmune disorders such as thyroid dysfunction, diabetes mellitus, or rheumatoid diseases were present in 139 patients (48,6%). Sustained clinical remission was reported by 102 patients (35,7%), 137 patients (47,9%) of them received medication such as corticosteroids, antibiotics, bismuth or 5-aminosalicyclic. In 22 patients (7,7%) empiric treatment was not effective 49 patients (17,1%) were regularly using Aspirin or NSAIDs. Conclusion: Collagenous colitis is frequently diagnosed in elderly female patients and often associated with abdominal pain, nocturnal stools, weight loss and concomitant autoimmune disorders. Overall response rates under empiric treatment were disappointing.
AGA Abstracts
(*) Human immunodeficiency virus W1040 Small Intestinal Bacterial Overgrowth and Oral Anticoagulant Therapy Emidio Scarpellini, Maurizio Gabrielli, Angelo Santoliquido, Tommaso Za, Elena Rossi, Ernesto Cristiano Lauritano, Andrea Lupascu, Veronica Ojetti, Giovanni Cammarota, Giovanni Gasbarrini, Valerio De Stefano, Antonio Gasbarrini Background and Aims: Vitamin K is available in humans in two different forms: phylloquinone (PLQ) present in green leafy vegetables and menaquinone (MNQ) synthesized by intestinal bacterial microflora. MNQ accounts for 50% of available vitamin K. Small intestinal bacterial overgrowth (SIBO) is a clinical condition due to a microrganisms increase to a level exceeding the presence of more than 106 CFU/mL of intestinal aspirate or of colonic-type bacteria within the small intestine. The qualitative and quantitative changes of intestinal bacterial microflora occurring in SIBO could affect MNQ synthesis and/or absorption. Aim of the study was to assess if SIBO influences dosage of warfarin in patients (pts) undergoing chronic treatment with oral anticoagulants (OAT). Methods: Pts receiving warfarin treatment for venous thromboembolism (VT) were consecutively enrolled from our Outpatients Unit of Haematology. Target International Normalized Ratio (INR) ranged 2-3 according to literature.
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patients (44.4%) had a divergent diagnosis (23 patients originally identified as CD and 1 diagnosed as non CD) (Cohen's kappa statistic for the overall agreement: 0.19). Misdiagnosis was mainly produced by an over diagnosis of CD (53.5% vs. 9.1%; OR: 11.5, 95% CI 1.3597.9; p<0.02). Compared with the gold standard serology, 39 patients (72.2%) had congruent results in practice (Cohen's kappa: 0.45) On the other hand, compared with the gold standard histological review, 28 samples (51.8%) had congruent diagnoses by the external pathologists (Cohen's kappa: 0.14). Misinterpretation was mainly due to a wrong diagnosis of enteropathy in non CD cases (OR: 30.0; 95% CI 5.7-157.7; p<0.0001). Conclusions: Our study detected a high rate of serological and histopathological misdiagnosis of CD in clinical practice. This was mainly due to a histologic overdiagnosis of CD. Although the nature of consultations in our referral center suggests a potential overestimation of the true prevalence of the problem, pitfalls in clinical practice may have profound negative impact on patients.
W1038 From Intra- to Extra-Gastric Role of Helicobacter pylori: Implications On Metabolic Syndromes Mohammad Khaled Helicobacter pylori (H. pylori) is well known for its association with many gastric ailments, particularly gastric ulcers leading to gastric cancer. Controversial reports exist in the literature on the association of H. pylori with coronary heart disease (CHD). This bacterium is highly prevalent in Bangladeshi populations in concomitant with the prevalence of CHD. This prompted us to investigate any possible role of H. pylori in the initiation and/or aggravation cardiovascular diseases. Using a cross-sectional analytic (case-control) design, 72 subjects were recruited who underwent coronary angiography to diagnose CHD. Based on the arterial narrowing of ≥ 50%, 40 (55%) of these subjects were diagnosed with CHD, while 32 (44%) were found to be normal. Demographic data, history, findings of physical examinations were recorded. Levels of fasting serum glucose, TG, HDL, TC were measured by the enzymatic photometry, while insulin, anti-H. pylori IgG antibody, CRP and thromboxane (TXB) were measured by enzyme immunoassay. The insulin resistance and insulin secretory defect were estimated using HOMA-CIGMA software. H. pylori cytotoxin-associated (cagA) and vacuolization cytotoxin (vacA) were detected by Western blot analysis. A total of 26 (65%) CHD patients (cases) and 16 (50%) normal (control) subjects were seropositive for H. pylori infection. Logistic regression analyses revealed that H. pylori (vacA) (β= -1.896, p=0.049) and insulin secretory defect (β= 6.911, p=0.013) are independent predictors of CHD. H. pylori (vacA) was also significantly associated with higher levels of fasting glucose (p=0.047), insulin resistance (p=0.044), CRP (p=0.05) and TXB (p=0.049). These findings suggest, for the first time to our knowledge, that the extragastric pathogenicity of H. pylori (vacA) may be mediated by influencing the metabolic syndromes, like insulin resistance and CRP, and by affecting insulin secretion from the pancreatic β-cells, as found in this study.
W1036 Do Tissue Transglutaminase Antibodies in Celiac Disease Contribute to Thyroid Autoimmunity? Afzal J. Naiyer, Jayesh Shah, Jianfeng Cheng, Lincoln Hernandez, Edward J. Ciaccio, John S. Manavalan, Govind Bhagat, Peter H. Green Aim: Celiac disease is associated with autoimmune thyroid disorders. Thyroid dysfunction in patients with active celiac disease (ACD) improves on institution of gluten-free diet (GFD). We thus determined whether tissue transglutaminase-2 IgA antibodies (anti-TG2) have a role in the development of thyroid autoimmunity. Methods: Serum from 40 ACD patients, prior to commencing a gluten-free diet, 46 patients on a GFD, 40 healthy (NC) and 25 disease control (DC) subjects were used. All sera were screened for anti thyroperoxidase (ATPO) and thyroglobulin (ATG) antibodies, thyroid stimulating harmone (TSH) and freeT4 (FT4) levels. Indirect immunofluorescence (IIF) was performed on primate thyroid tissue sections using anti-thyroid seronegative sera. Results: IIF with thyroid seronegative, antiTG2 positive ACD sera (n=21) demonstrated staining of thyroid follicular cells as well as extracellular matrix in the interfollicular areas. The IIF patterns of monoclonal anti-human TG2 antibody and patient sera with anti-TG2 were superimposeable. Evidence of TG2 as the antigen was supported by complete abrogation of the IIF pattern when patient sera was depleted of anti-TG2 by pretreatment with human recombinant TG2 or recombinant TG2 bound beads. No staining was observed with sera from patients on GFD and negative antiTG2 or in normal and disease controls. In order to observe the clinical significance of the binding of anti-TG2 to thyroid tissue we assessed thyroid autoimmunity in the study population. Thyroid antibodies were found in 43% ACD patients, significantly higher than NC and DC (p<0.0001). There was a positive correlation between the anti-TG2 and ATPO titers (p=0.0001; r=0.63). Furthermore the mean age of ACD patients was significantly higher in the presence of ATPO antibodies than in its absence (50.3 ± 3.1 vs 36.3 ± 3.7, = 0.01). Overall there was no age difference between active celiac disease, GFD and healthy controls with the exception of the disease control group which was significantly older than the ACD group (50.2 ± 3.3 vs 41.7 ± 2.4, p =0.03). Thyroid dysfunction was identified in 8 ACD patients, 4 had a past medical history of autoimmune thyroid disease with the other 4 with no prior thyroid disease. Conclusions: Thyroid disease is common in celiac patients. Anti-TG2 antibodies in untreated celiac disease bind to TG2 in thyroid tissue. A positive correlation exists between of anti-TG2 and ATPO titers in active celiac patients. Our data suggests that anti-TG2 may play a role in the development of thyroid autoimmunity in celiac disease. This may be may be more important in older celiac disease patients.
W1039 Helicobacter pylori Infection and Impaired Drug Absorption: A Systematic Review Edith Lahner, bruno annibale, Gianfranco Delle Fave Background & Aim: Drug absorption influences the efficacy of orally administered therapy and gastric secretion may affect drug absorption. Impaired gastric acid secretion is a common consequence of H pylori-induced gastritis, mainly in corpus. Thus, H pylori-induced gastritis may potentially affect the absorption of orally administered drugs. This review is aimed to focuse on the evidence of impaired drug absorption associated with H pylori infection. Data Sources: Systematic search of MEDLINE/ EMBASE databases (1980-September 2007) for English-language articles using the keywords drug malabsorption and absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study Selection: From 2,099 retrieved articles, 5 studies were identified (1 randomized controlled trial, 2 controlled crossover studies, 1 case-control study, and 1 case series) showing a significant variation in study population and design and type of intervention. Data Extraction: From each selected paper, information on the investigated drug, type of the study, main features of investigated subjects, study design, type of intervention, and study results were extracted. Results: 5 studies investigated the absorption of drugs (three) in association with H pylori infection: L-dopa, thyroxine, and delavirdine. H pylori infection was assessed by serology in 3 studies and also by histology in 2 studies. In 4 studies drug absorption was investigated with respect to eradication treatment and in 2 studies with respect to gastric acidity. Impaired absorption was reported in association with H pylori infection. (Table). Conclusions: A plausible mechanism of impaired drug absorption is the reduced gastric acid secretion in pts with H pylori gastritis. The H pylori infection and the associated hypochlorhydria, should be considered in prescribing drugs whose absorption is potentially affected by the intragastric pH.
W1037 Collagenous Colitis: Clinical Presentation, Treatment and Outcome of 287 Patients Ahmed Madisch, Stephan Miehlke, Franziska Bartosch, Birgit Bethke, Manfred Stolte Background: Collagenous colitis is a chronic disorder characterized by watery diarrhea. Clinical features or treatment outcomes in a large group of patients are sparse and only retrospectively collected. Aim: to evaluate prospectively the clinical features, response to treatment and outcomes in a large group of patients with collagenous colitis. Patients and Methods: Patients with histologically confirmed collagenous colitis were prospectively enrolled to complete a questionnaire on onset and duration of diarrhea, stool frequency and consistency, other gastrointestinal symptoms including weight loss, drug history, treatment success and concomitant diseases. Results: A total of 286 patients (female n=220 (76,9%); mean age 65,81 years, range 35-92 years) were available for analysis. Prior to diagnosis the mean duration of symptoms was 37,1 months (range 2 days to 30,41 years). At diagnosis the daily mean stool frequency was 6,88 (range 1-42). Abdominal pain were reported by 99 patients (34,6%), weight loss (mean 3,23 kg) by 140 patients (49%) and nocturnal stools by 185 patients (64,7%). Concomitant autoimmune disorders such as thyroid dysfunction, diabetes mellitus, or rheumatoid diseases were present in 139 patients (48,6%). Sustained clinical remission was reported by 102 patients (35,7%), 137 patients (47,9%) of them received medication such as corticosteroids, antibiotics, bismuth or 5-aminosalicyclic. In 22 patients (7,7%) empiric treatment was not effective 49 patients (17,1%) were regularly using Aspirin or NSAIDs. Conclusion: Collagenous colitis is frequently diagnosed in elderly female patients and often associated with abdominal pain, nocturnal stools, weight loss and concomitant autoimmune disorders. Overall response rates under empiric treatment were disappointing.
AGA Abstracts
(*) Human immunodeficiency virus W1040 Small Intestinal Bacterial Overgrowth and Oral Anticoagulant Therapy Emidio Scarpellini, Maurizio Gabrielli, Angelo Santoliquido, Tommaso Za, Elena Rossi, Ernesto Cristiano Lauritano, Andrea Lupascu, Veronica Ojetti, Giovanni Cammarota, Giovanni Gasbarrini, Valerio De Stefano, Antonio Gasbarrini Background and Aims: Vitamin K is available in humans in two different forms: phylloquinone (PLQ) present in green leafy vegetables and menaquinone (MNQ) synthesized by intestinal bacterial microflora. MNQ accounts for 50% of available vitamin K. Small intestinal bacterial overgrowth (SIBO) is a clinical condition due to a microrganisms increase to a level exceeding the presence of more than 106 CFU/mL of intestinal aspirate or of colonic-type bacteria within the small intestine. The qualitative and quantitative changes of intestinal bacterial microflora occurring in SIBO could affect MNQ synthesis and/or absorption. Aim of the study was to assess if SIBO influences dosage of warfarin in patients (pts) undergoing chronic treatment with oral anticoagulants (OAT). Methods: Pts receiving warfarin treatment for venous thromboembolism (VT) were consecutively enrolled from our Outpatients Unit of Haematology. Target International Normalized Ratio (INR) ranged 2-3 according to literature.
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