Natalia E. Castillo

The present and the future in the diagnosis and management of celiac disease

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies—including gluten modification, modulation of intestinal permeability and immune response—could be central to the future treatment of celiac disease.

Prevalence of Abnormal Liver Function Tests in Celiac Disease and the Effect of a Gluten-Free Diet in the US Population

OBJECTIVES:Guidelines recommend routine screening of liver function tests (LFTs) in patients diagnosed with celiac disease (CD). However, little is known about the prevalence of liver disorders in CD outside of Europe. Our aims were to estimate the prevalence of LFT abnormalities in CD and to evaluate the effect of a gluten-free diet (GFD) on LFTs.METHODS:Adult patients with biopsy-proven CD were identified from a prospectively maintained database and matched with healthy controls. LFT levels for women and men were defined as abnormal based on the Third National Health and Nutrition Examination Survey (NHANES III) criteria. Data on demographics, coexisting liver diseases, and laboratory work-ups including aspartate transaminase (AST) and alanine transaminase (ALT) values at the time of diagnosis and on a GFD were recorded. Subsequently, data from this cohort were compared with data from 7,789 individuals participating in the National Health and Nutrition Examination Survey, 2009–2010. Univariate logistic regression, Wilcoxon signed-ranks, Student’s t-test, χ2, and Fischer’s exact test were used for statistical analysis.RESULTS:In 463 CD patients with ALT or AST levels at the time of CD diagnosis, 40.6% had elevated LFTs compared with 24.2% of treated CD patients (P<0.001) and 16.6% of matched controls (P<0.001). Similarly, 36.7% of CD patients on the NHANES database had abnormal ALT values compared with 19.3% of non-celiac patients (P=0.03). Approximately, 78.6% of CD patients with elevated LFTs at diagnosis normalized LFTs on a GFD after a mean duration of 1.5±1.5 years.CONCLUSIONS:Forty percent of individuals will have elevated LFTs at CD diagnosis; however, the majority will normalize with standard CD therapy. LFTs should be checked in all patients with CD and coexisting liver disorder should be considered in patients whose LFTs have not improved within a year on a GFD.

Poor Documentation of Inflammatory Bowel Disease Quality Measures in Academic, Community, and Private Practice

BACKGROUND & AIMS Quality measures are used to standardize health care and monitor quality of care. In 2011, the American Gastroenterological Association established quality measures for inflammatory bowel disease (IBD), but there has been limited documentation of compliance from different practice settings. METHODS We reviewed charts from 367 consecutive patients with IBD seen at academic practices, 217 patients seen at community practices, and 199 patients seen at private practices for compliance with 8 outpatient measures. Records were assessed for IBD history, medications, comorbidities, and hospitalizations. We also determined the number of patient visits to gastroenterologists in the past year, whether patients had a primary care physician at the same institution, and whether they were seen by a specialist in IBD or in conjunction with a trainee, and reviewed physician demographics. A univariate and multivariate statistical analysis was performed to determine which factors were associated with compliance of all core measures. RESULTS Screening for tobacco abuse was the most frequently assessed core measure (89.6% of patients; n = 701 of 783), followed by location of IBD (80.3%; n = 629 of 783), and assessment for corticosteroid-sparing therapy (70.8%; n = 275 of 388). The least-frequently evaluated measures were pneumococcal immunization (16.7% of patients; n = 131 of 783), bone loss (25%; n = 126 of 505), and influenza immunization (28.7%; n = 225 of 783). Only 5.8% of patients (46 of 783) had all applicable core measures documented (24 in academic practice, none in clinical practice, and 22 in private practice). In the multivariate model, year of graduation from fellowship (odds ratio [OR], 2.184; 95% confidence interval [CI], 1.522-3.134; P < .001), year of graduation from medical school (OR, 0.500; 95% CI, 0.352-0.709; P < .001), and total number of comorbidities (OR, 1.089; 95% CI, 1.016-1.168; P = .016) were associated with compliance with all core measures. CONCLUSIONS We found poor documentation of IBD quality measures in academic, clinical, and private gastroenterology practices. Interventions are necessary to improve reporting of quality measures.

Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers

ABSTRACT Probiotics are believed to be beneficial in maintaining a healthy gut microbiota whereas antibiotics are known to induce dysbiosis. This study aimed to examine the effects of the probiotic Saccharomyces boulardii CNCM I-745 (SB), the antibiotic Amoxicillin-Clavulanate (AC) and the combination on the microbiota and symptoms of healthy humans. Healthy subjects were randomized to one of 4 study groups: SB for 14 days, AC for 7 days, SB plus AC, Control (no treatment). Participants gave stool samples and completed gastro-intestinal symptom questionnaires. Microbiota changes in stool specimens were analyzed using 16s rRNA gene pyrosequencing (bTEFAP). Only one subject withdrew prematurely due to adverse events. Subjects treated by S boulardii + AC had fewer adverse events and tolerated the study regimen better than those receiving the AC alone. Control subjects had a stable microbiota throughout the study period. Significant microbiota changes were noted in the AC alone group during antibiotic treatment. AC associated changes included reduced prevalence of the genus Roseburia and increases in Escherichia, Parabacteroides, and Enterobacter. Microbiota alterations reverted toward baseline, but were not yet completely restored 2 weeks after antibiotherapy. No significant shifts in bacterial genera were noted in the SB alone group. Adding SB to AC led to less pronounced microbiota shifts including less overgrowth of Escherichia and to a reduction in antibiotic-associated diarrhea scores. Antibiotic treatment is associated with marked microbiota changes with both reductions and increases in different genera. S. boulardii treatment can mitigate some antibiotic-induced microbiota changes (dysbiosis) and can also reduce antibiotic-associated diarrhea.

Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality

Objectives The objective of this study was to determine our institutions compliance with 2010 Society for Healthcare Epidemiology of America and IDSA Clostridium difficile infection (CDI) treatment guidelines and their respective outcomes. Methods We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality. Results We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (P < 0.0001) and 10.9% in those appropriately treated plus over-treated (P < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (P = 0.03) and 8.2% in those either appropriately treated or over-treated (P = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, P = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, P = 0.023). Conclusions Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.

847 Evaluation of Antibodies to Cytolethal Distending Toxin B (CdtB) and Vinculin in Celiac Disease

Background: Patients with refractory gastroesophageal reflux disease (GERD) may have undiagnosed celiac disease. These patients often undergo esophagogastroduodenoscopy to determine the etiology and severity of GERD. Because a duodenal biopsy is the gold standard for diagnosing celiac disease and a gluten-free diet is an effective treatment, performing routine duodenal biopsy during endoscopy may result in early diagnosis and symptom improvement, allowing for discontinuation of proton pump inhibitor therapy. We aimed to evaluate the cost-effectiveness of performing routine duodenal biopsy during endoscopy for diagnosing celiac disease in patients with refractory GERD. Methods: We constructed a decision tree using data from published literature to calculate cost-effectiveness of endoscopy with and without duodenal biopsy in a cohort of 10,000 40-year-old patients. Results: We found that the biopsy strategy would detect 70 out of 100 celiac disease patients in a cohort of 10,000 GERD patients undergoing endoscopy if the prevalence of celiac disease was 1% in this cohort. Up-front biopsy would increase the remaining quality-adjusted life years (QALYs) by 0.0032. Testing for celiac disease using this approach would increase the lifetime cost by

Sa1304 Bone Mineral Density in Celiac Disease

389 per patient. Compared with no biopsy, the biopsy strategy cost

Celiac Disease as a Model Disorder for Testing Novel Autoimmune Therapeutics

55,693 per celiac case detected, and

Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005–2013) for Barrett’s Esophagus

121,875 per QALY gained. The incremental cost-effectiveness ratio (ICER) met the threshold of 1.8%, the specificity of biopsy was >98%, the cost of gluten-free diet was

999 Prevalence and Clinical Risk Factors of Nonresponsive Celiac Disease in Children

5,874 per year. Increasing the sensitivity of duodenal biopsy to 100% did not affect the cost-effectiveness threshold. Conclusion: Esophagogastroduodenoscopy with duodenal biopsy for refractory GERD patients can be a cost-effective approach for screening when the prevalence of celiac disease in this patient population is 1.8% or greater.