Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

ROC-king onwards: intraepithelial lymphocyte counts, distribution & role in coeliac disease mucosal interpretation.

OBJECTIVES: Counting intraepithelial lymphocytes (IEL) is central to the histological diagnosis of coeliac disease (CD), but no definitive 'normal' IEL range has ever been published. In this multicentre study, receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off between normal and CD (Marsh III lesion) duodenal mucosa, based on IEL counts on >400 mucosal biopsy specimens. DESIGN: The study was designed at the International Meeting on Digestive Pathology, Bucharest 2015. Investigators from 19 centres, eight countries of three continents, recruited 198 patients with Marsh III histology and 203 controls and used one agreed protocol to count IEL/100 enterocytes in well-oriented duodenal biopsies. Demographic and serological data were also collected. RESULTS: The mean ages of CD and control groups were 45.5 (neonate to 82) and 38.3 (2-88) years. Mean IEL count was 54±18/100 enterocytes in CD and 13±8 in normal controls (p=0.0001). ROC analysis indicated an optimal cut-off point of 25 IEL/100 enterocytes, with 99% sensitivity, 92% specificity and 99.5% area under the curve. Other cut-offs between 20 and 40 IEL were less discriminatory. Additionally, there was a sufficiently high number of biopsies to explore IEL counts across the subclassification of the Marsh III lesion. CONCLUSION: Our ROC curve analyses demonstrate that for Marsh III lesions, a cut-off of 25 IEL/100 enterocytes optimises discrimination between normal control and CD biopsies. No differences in IEL counts were found between Marsh III a, b and c lesions. There was an indication of a continuously graded dose-response by IEL to environmental (gluten) antigenic influence.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Helicobacter pylori prevalence and risk factors among children with celiac disease.

BACKGROUND/AIMS: The relationship between Helicobacter pylori and celiac disease (CD) remains controversial. The aim of this study was to assess the prevalence and risk factors for H. pylori infection among children diagnosed with CD. MATERIALS AND METHODS: This study included 70 patients diagnosed with CD at a tertiary referral center in Romania. Age, gender, and indicators of environmental conditions were evaluated via interviews with the children's caretakers. A multivariable logistic regression analysis was performed to identify the independent predictors for H. pylori infection. RESULTS: Of the 70 patients, 37 (52.9%) were females, and the mean age was 4.04±3.26 years. H. pylori infection was diagnosed in 23 (32.8%) patients, of whom 12 (52.1%) were females, and the mean age was 6.2±4.5 years. Of the total number of children with CD and H. pylori infection, 18 (78.2%) had milder forms of enteropathy (Marsh I-II), whereas the remaining 5 (21.7%) had villous atrophy compared to the other 47 (67.2%) patients who were negative for H. pylori-infection and showed more severe intestinal damage. The development of H. pylori infection was independently related to children with one parent only [odd ratio (OR), 9.04; 95% confidence interval (CI), 1.29-62.89; p<0.001], living in houses without sanitary facilities (OR, 3.88; 95% CI, 1.27-14.22; p=0.016), belonging to low-income families (OR, 8.52; 95% CI, 2.52-71.39; p=0.002), and of parents with a prior history of gastritis (OR, 2.68; 95% CI, 1.49-14.50; p=0.004). CONCLUSION: Children with CD and H. pylori infection had milder forms of enteropathy compared to children who are negative for H. pylori, suggesting that H. pylori infection may confer some protection against the development of severe degrees of villous atrophy.

Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran's Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS: Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION: This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.

Incidence and risk factors of Clostridium difficile infection in patients with inflammatory bowel disease.

UNLABELLED: Recent changes in the epidemiology of Clostridium difficile infection (CDI) include the identification of patients with inflammatory bowel disease (IBD) as a group at risk in comparison to the general population. AIM: To identify the incidence and risk factors for CDI among patients with IBD. MATERIAL AND METHODS: Case-control study of 78 patients diagnosed with IBD, hospitalized at the Iasi Institute of Gastroenterology and Hepatology between January 2012 and -July 2014. Demographic data and clinical characteristics were reviewed for all patients. IBD patients with positive C. difficile toxins A and B tests were matched by sex, age and type of IBD with IBD patients hospitalized in the same period with negative C. difficile toxins tests. RESULTS: Both groups were comparable for baseline characteristics. Of the 78 patients diagnosed with IBD included in the study, C. difficile was detected in 26 patients (33.33%). There was no statistical difference regarding length of hospital stay (10.42 ± 7.34 vs. 8.01 ± 16.14 days, p = 0.129) between the two study groups. Risk factors for CDI in patients with IBD were: ulcerative colitis (OR = 1.90, CI = 1.320-2.720, p = 0.001), use of proton pump inhibitors (OR = 1.57, CI = 1.133-2.032, p = 0.012), previous antibiotic use (OR = 2.3, CI = 1.587-3.332, p < 0.0001), and albumin < 3 g/dl (OR = 1.78, CI = 1.023-5.558, p = 0.038). Immunosuppressive and anti TNF-α treatment were not risk factors for C. difficile development in patients with IBD. CONCLUSIONS: CDI in patients with IBD is a serious infection and should be treated aggressively with close clinical follow-up. Ulcerative colitis, previous treatment with antibiotics and proton pump inhibitors represent risk factors for CDI development in patients with IBD.

Metastatic carcinoid tumor--atypical presentation.

Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in the enterochromaffin cells and secreting mainly serotonin. Neuroendocrine tumors (NETs) are found throughout the intestinal tract, the appendix and terminal ileum being the most common locations, and are classified by site of origin and by degree of differentiation, with well-differentiated lesions representing those tumors formerly referred to as carcinoid tumors. The clinical symptoms are characterized by flushing, diarrhea, abdominal pain, and/or bronchial constriction and occur almost exclusively in patients with liver metastases due to the release of bioactive peptides and amines directly into the systemic circulation. We report the clinical, serological and histological diagnosis of a 67-years-old male patient with congestive heart failure secondary to carcinoid heart disease in the context of liver metastases of an ileum carcinoid tumor.

Celiac disease: 10-year experience in a Romanian tertiary center.

AIM: To evaluate the experience of a single coeliac center over a 10-year-observational period. MATERIAL AND METHODS: Between January 2003 and December 2013 a total of 195 consecutive patients admitted with celiac disease were tested by multiple duodenal biopsies, anti-tissue transglutaminase and anti-gliadin antibodies, and baseline demographic, clinical, biological and immunological parameters. RESULTS: Patients were divided into two major groups according to the clinical features and number of signs and symptoms present upon admission: gastrointestinal (131, 67.17%) and non-gastrointestinal (64, 32.8%). Anti-tissue transglutaminase and anti-gliadin antibodies showed seropositivity in 109/158. Histological samples were available in 152 cases, according to Marsh-Oberhuber classification 11.18% being type 0, 17.76%, type I-II, and 71.05% type III. Correlations between anti-tissue transglutaminase antibody titers and Marsh-Oberhuber classification were found to be statistically significant. Body mass index was available in 96 cases. We found that severe atrophy was predominant in patients with a BMI<18 kg/m2. CONCLUSIONS: Celiac disease has an increasing prevalence and can be diagnosed at any age. Histology samples were indicative of different stages of villous atrophy. The disease prevalence is significantly higher among women. There was no statistically significant correlation between Marsh classification and BMI values.