Time Of Celiac Disease Diagnosis Research Articles

Coeliac Disease Case–Control Study: Has the Time Come to Explore beyond Patients at Risk?

The worldwide prevalence of asymptomatic coeliac disease (CD) is increasing, which is in part due to the routine screening of children with risk factors. Both symptomatic and asymptomatic patients with CD are at risk of long-term complications. The objective of this study was to compare the clinical characteristics of asymptomatic and symptomatic children at the time of CD diagnosis. A case-control study was conducted using data from a cohort of 4838 CD patients recruited from 73 centers across Spain between 2011 and 2017. A total of 468 asymptomatic patients (cases) were selected and matched by age and sex with 468 symptomatic patients (controls). Clinical data, including any reported symptoms, as well as serologic, genetic, and histopathologic data were collected. No significant differences were found between the two groups in most clinical variables, nor in the degree of intestinal lesion. However, the asymptomatic patients were taller (height z-score -0.12 (1.06) vs. -0.45 (1.19), p < 0.001) and were less likely to have anti transglutaminase IgA antibodies ≥ 10 times the upper normal limit (66.2% vs. 758.4%, p = 0.002). Among the 37.1% of asymptomatic patients who were not screened for CD due to the absence of risk factors, only 34% were truly asymptomatic, while the remaining 66% reported non-specific CD-related symptoms. Therefore, expanding CD screening to any child who undergoes a blood test could reduce the burden of care for some children, as many of those considered asymptomatic reported non-specific CD-related symptoms.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.

Helicobacter pylori infection and celiac disease in children, what is the relationship?

Background: Celiac disease (CD) is an autoimmune disease affecting the small intestine, triggered by gluten. The pathogenesis of CD has been well defined, and the increasing prevalence of this disease had led to studying several environmental risk factors that may trigger an autoimmune process in the small intestine. Infection is one of the most important factors that can trigger autoimmune processes. The researchers have studied the association between H. pylori infection and CD, the authors have reported conflicting results. Purpose: to study the association of H. pylori and celiac disease (CD) at the time of CD diagnosis in children. Patient and Methods: All patients in the study were subjected to full history taking, thorough clinical examination, and laboratory investigations including Anti-tissue transglutaminase antibodies (IgA), anti-endomysial (IgA EMA), Stool Ag for H. pylori, CLO test for H. pylori, Immunoglobulins level, Upper gastrointestinal endoscopy with multiple biopsies for histopathological examination. Results: Anti TTG Ig A and Endomysial Ab were positive in 49 patients, while one patient showed negative results. 7 patients (14%) had H.

Bi-directional Relationship Between Celiac Disease and Liver Chemistries: A Systematic Review and Meta-Analysis.

Previous studies have reported conflicting results regarding prevalence of elevated LC (2-70%) in celiac disease (CD). This systematic review and meta-analysis assessed the prevalence of elevated LC at time of CD diagnosis and associated response to GFD. We also report the prevalence of CD in patients with unexplained elevation of LC. Studies assessing LC (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) in CD patients were eligible. Studies with < 50 cases or in pediatric populations were excluded. In total, 20 studies assessing prevalence of elevated LC in 4,265 participants with newly diagnosed CD (mean age = 35.6 ± 6.5years, 69.8% female) were included. Pooled prevalence of elevated LC was 18.7% (95% CI 13.8-24.8; I2 = 95%). Normalization of elevated LC was seen in 83.1% (95% CI 73.4-89.7; I2 = 79%, 11 studies) of patients after GFD. On meta-regression, age at CD diagnosis, gender, and Marsh grading were not associated with elevated LC. Among 979 participants (7 studies) with unexplained elevation of LC, pooled seroprevalence and biopsy-proven CD was 6.4% (95% CI 2.9-10.3, I2 = 71%) and 4.5% (95% CI 2.6-7.7, I2 = 67%), respectively. Elevated LC are seen in approximately one-fifth of patients at CD diagnosis with majority normalizing after GFD. Age, gender, and degree of intestinal damage are not predictive of elevated LC. In the appropriate clinical scenario, liver tests should be serially monitored in CD reserving workup for additional causes after a trial of GFD. Patients with unexplained elevation of liver tests should be screened for celiac disease.

A194 THE ADDITION OF DEAMIDATED GLIADIN PEPTIDE TO TISSUE TRANSGLUTAMINASE ANTIBODIES DOES NOT INCREASE THE ODDS OF CELIAC DISEASE DIAGNOSIS IN AN IGA SUFFICIENT POPULATION

BackgroundPrevious studies proposed that the combination of IgA anti-tissue transglutaminase 2 IgA (TTG) and IgG deamidated gliadin peptide IgG (DGP) antibodies increases celiac disease (CeD) detection rates. However, this remains controversial.AimsTo evaluate the performance of adding DGP to TTG antibodies, for the diagnosis of celiac disease (CeD) in the immunoglobulin A (IgA)-sufficient population.MethodsWe included consecutive patients with suspected CeD who had both TTG and DGP serology performed simultaneously from 2017–2020 in Hamilton, Canada. Chart review was performed by 3 reviewers to extract data on biopsies, diagnosis of CeD and genetic HLA-DQ2/DQ8. CeD was defined as positive serology (either TTG and/or DGP) and villous atrophy in duodenal biopsies (≥Marsh-3a). A case was defined as an instance of TTG and DGP performed at a single timepoint. A single patient could have represented multiple cases if TTG and DGP were measured at multiple time points. Sensitivity, specificity, negative and positive predictive values were calculated, and ROC curves were generated. Diagnostic odds ratios (DOR) assessed the performance of each serological strategy compared to duodenal biopsies.ResultsThere were 580 patients constituting 823 cases that met inclusion criteria, of whom 441 had CeD. IgA-deficient patients (n=100) were excluded. Of the 723 cases remaining, 337 (214 adult;123 pediatric) had serology performed at the time of CeD diagnosis. TTG increased the odds of CeD diagnosis compared with DGP, Diagnostic Odds Ratio (DOR)=53.22 (95% CI 22.63–119.80) vs DOR=21.28 (95% CI 10.67–42.46). The addition of DGP to TTG did not increase the odds of CeD diagnosis [DGP+TTG DOR=51.39 (95% CI 19.36–135.61) vs TTG alone DOR=53.22 (95% CI 22.63–119.80)]. There were 37 discordant cases where only one of either TTG or DGP was positive. HLA-DQ2/DQ8 were absent in 2/9 cases with isolated increased DGP. Among the discordant cases, TTG outperformed DGP (DOR TTG= 4.29; 95% CI 1.09–16.83 vs DOR DGP=0.23; 95% CI 0.06–0.92).ConclusionsIn the IgA-sufficient population, the addition of DGP to TTG testing does not increase the diagnostic accuracy of CeD serologic screening. This has implications in health-care costs as false positive results prompt further investigations. Given these findings, larger prospective studies should be completed prior to adding DGP antibodies to routine TTG serology.Funding AgenciesNone

Compliance to a Gluten-Free Diet in Swedish Children with Type 1 Diabetes and Celiac Disease.

Children with type 1 diabetes (T1D) are at increased risk of celiac disease (CD). The replacement of insulin in T1D, and the exclusion of gluten in CD, are lifelong, burdensome treatments. Compliance to a gluten-free diet (GFD) in children with CD is reported to be high, while compliance in children with both diseases has scarcely been studied. To examine compliance to a GFD in children with both T1D and CD, we analyzed tissue transglutaminase IgA-antibodies (tTGA). Moreover, associations between compliance and age, sex, glycemic control, ketoacidosis (DKA), body mass index (BMI), and time of CD diagnosis were investigated. Of the 743 children diagnosed with T1D in southern Sweden between 2005 and 2012, 9% were also diagnosed with CD. Of these, 68% showed good compliance to a GFD, 18% showed intermediate compliance, and 14% were classified as non-compliant. Higher age, poorer HbA1c, and more DKAs were significantly (p < 0.05) associated with poorer compliance. In conclusion, we found that compliance to a GFD in children with T1D and CD is likely be lower than in children with CD only. Our results indicate that children with both T1D and CD could need intensified dietary support and that older children and children with poor metabolic control are especially vulnerable subgroups.

Relationship between Persistent Gastrointestinal Symptoms and Duodenal Histological Findings after Adequate Gluten-Free Diet: A Gray Area of Celiac Disease Management in Adult Patients

A gluten-free diet (GFD) leads to a rapid improvement in gastrointestinal (GI) symptoms, biochemical alterations and duodenal histological damage in the majority of celiac disease (CD) patients. This study aimed to assess the frequency and factors associated with the persistence of GI symptoms/malabsorption signs and their relationship with duodenal histological findings among CD patients on an adequate GFD (mean duration 16 months, range 12–28 months). This longitudinal cohort study included 102 adult CD patients (median age 38.5 years, range 18–76 years, F = 71.6%) diagnosed between 2012 and 2018. A total of 36.3% of the included patients had persistent GI symptoms and/or malabsorption signs (Group 1), while the remaining patients had complete GI well-being without malabsorption signs (Group 2) at the time of histological re-evaluation. The persistence of GI symptoms/signs was associated with a long duration of symptoms/signs before CD diagnosis (≥5 years) (OR 5.3; 95% CI 1.3–21.8) and the presence of constipation at the time of CD diagnosis (OR 7.5; 95% CI 1.3–42) while for other variables, including age at CD diagnosis, sex, duration of GFD, comorbidities, CD serology positivity and severity of duodenal damage at histological re-evaluation, no association was found. According to our results, the persistence of symptoms/signs is not associated with histological findings, and their relationship could be a gray area in CD management.

Increased prevalence of celiac disease and its clinical picture among patients with diabetes mellitus type 1 - observations from a single pediatric center in Central Europe.

The aim of our study was to analyze the incidence and the clinical characteristic of celiac disease (CD) in pediatric population with type 1 diabetes mellitus (T1DM). The data of 880 patients with T1DM, 429 girls, mean age 12.14 ±4.0 years was retrospectively retrieved from medical records. Patients with T1DM and CD were selected and a detailed analysis of CD prevalence and its clinical characteristic at the time of CD diagnosis was performed. The data were compared with the previous data from our center published a decade ago. CD was suspected in 85/880 patients (9.65%) on the base of results of serological tests, but finally CD was diagnosed in 73/880 patients with T1DM (8.3%), in 53/429 girls (12.3%) and in 20/451 boys (4.4%). Most patients (71%) had CD diagnosed after T1DM onset. The majority of CD patients (72%) was asymptomatic. The CD diagnosis was not associated with inappropriate metabolic control of diabetes. The onset age of diabetes in children with CD was significantly lower than in those without CD (5.8 ±3.6 years vs. 7.56 ±4.0 years, p=0.04). The prevalence of CD is significantly higher than adecade ago in our center (8.3% vs. 5.7%, p=0.001). In light of increasing prevalence of mainly asymptomatic CD in patients with T1DM, CD screening is necessary. However positive serological tests, which are currently used in screening, and are the first step of diagnostics, in some patients allow only to suspect the CD and further diagnostic steps should be performed.

Change in Patient MELD-Na and Albumin Level From the Time of Celiac Disease Diagnosis to Six Months Later After Gluten-Free Diet.

Background & aimsCeliac disease (CD) is a multisystem disorder triggered by dietary gluten in genetically predisposed individuals that may affect any organ system, including the liver. We evaluated a change in patient model for end-stage liver disease (MELD)-Na and albumin level from the time of celiac disease diagnosis to six months later, after implementing a gluten-free diet.MethodsA retrospective study was conducted from January 1, 2006, to June 30, 2018. CD was diagnosed based on celiac antibodies and/or histopathological data. MELD-Na and albumin were calculated at the start of the gluten-free diet and six months later. Additional variables like gender, ethnicity, serum IgA level, serum IgG level, human leukocyte antigen (HLA) type, and markers of end-stage liver disease were collected. Descriptive statistics, including means, were reported with the standard deviation for the continuous variables along with frequencies and percentages for all categorical variables.ResultsA total of 18 patients (55.6% male) were identified as having both cirrhosis and CD. The mean age at the time of celiac diagnosis was 53.6, and 94.4% were Caucasian. CD was diagnosed using celiac antibodies (100%) and histopathological data (44.4%). Most common celiac antibodies include anti-tissue transglutaminase antibodies (77.8%). End-stage liver disease markers like abdominal ascites (55.6%), variceal bleed (50.0%), acute or chronic kidney injury (16.7%), hepatocellular carcinoma (HCC) (11.1%), hepatic encephalopathy (HE) (50.0%), spontaneous bacterial peritonitis (SBP) (5.6%), and liver transplant (0.0%) were seen. The mean baseline MELD-Na score was 11.8, and albumin was 3.5 at the time of celiac diagnosis and mean MELD-Na was 11.8, and albumin was 3.5 six months after a gluten-free diet.ConclusionIt is difficult to conclude any exact relationship between change in MELD-Na score after gluten-free diet, but an improving trend is noted in patients with higher MELD-Na score such as 17 or higher. There is no change or worsening of MELD-Na score in patients with lower MELD-Na score. There was no change in mean MELD-Na and albumin level after gluten-free diet.

Overall and Cause-Specific Mortality in Adult Celiac Disease and Dermatitis Herpetiformis Diagnosed in the 21st Century.

We assessed whether celiac disease-associated mortality is increased in Finland among patients diagnosed in the 21st century, given recent improvements in diagnostic and treatment facilities. Biopsy-proven patients with celiac disease (Marsh III) and dermatitis herpetiformis aged 20-79 years (median 50 years) diagnosed 2005-2014 (n = 12,803) were identified from the national dietary grant registry. Dates and causes of death were obtained from Statistics Finland. Overall mortality and causes of death were compared with reference individuals (n = 38,384) matched for age, sex, and area of residence (at the time of celiac disease diagnosis) selected from the Population Information System. During a mean follow-up of 7.7 years (SD ±3.0 years), 884 (6.9%) and 2,613 (6.8%) deaths occurred among the celiac cohort and reference group, respectively. Overall mortality (hazard ratio [HR] 1.01, 95% confidence intervals [CIs] 0.94-1.09), mortality from all malignancies (HR 1.11, 95% CI 0.96-1.27), gastrointestinal tract malignancies (HR 1.21, 95% CI 0.56-1.71), or cardiovascular diseases (HR 0.91, 95% CI 0.77-1.07) were not increased among patients with celiac disease. Overall, mortality from lymphoproliferative diseases (HR 2.36, 95% CI 1.65-3.39) and nonmalignant digestive diseases (HR 2.19, 95% CI 1.40-3.43) was increased, but HRs decreased after the exclusion of the first 2 years of follow-up (HR 1.71, 95% CI 1.10-2.66 and HR 1.75, 95% CI 1.01-3.05, respectively). The overall mortality in adult celiac disease diagnosed 2005-2014 was not increased. Mortality from lymphoproliferative diseases was increased but lower than previously reported.

Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing.

Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. Median age at the time of CD diagnosis was 56 years (range 18-91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.

Micronutrient Deficiencies Are Common in Contemporary Celiac Disease Despite Lack of Overt Malabsorption Symptoms

ObjectiveTo evaluate micronutrient deficiencies in a contemporary cohort of adult patients with newly diagnosed celiac disease (CD). Patients and MethodsThis is a retrospective study of prospective adults newly diagnosed with CD from January 1, 2000, through October 31, 2014, at Mayo Clinic. Micronutrient data were collected for tissue transglutaminase IgA, zinc, 25-hydroxy vitamin D, ferritin, albumin, copper, vitamin B12, and serum folate. Data were analyzed for absolute number of deficiencies and associations with age, sex, body mass index, presenting symptoms, and tissue transglutaminase IgA; each deficiency was assessed using logistic regression. Deficiencies were compared with age- and sex-matched controls from the National Health and Nutrition Examination Survey. ResultsIn total, 309 patients with CD (196 women and 113 men; mean age, 46.1±15.1 years; mean body mass index, 25.9 kg/m2) were included. Weight loss was seen in only 25.2% (78/309) of patients. Zinc was deficient in 59.4% (126/212) of patients with CD compared with 33.2% (205/618) of controls (P<.001). Albumin was low in 19.7% (24/122) compared with 1.1% of controls (P<.001). Copper was low in 6.4% (13/204) compared with 2.1% (13/618) of controls (P=.003). Vitamin B12 was low in 5.3% (13/244) compared with 1.8% (11/618) of controls (P=.004). Folate was low in 3.6% (6/159) compared with 0.3% (2/618) of controls (P=.002). 25-Hydroxy vitamin D was low in 19.0% (44/213) compared with 18% (111/618) of controls (P=.72). Ferritin was low in 30.8% (66/214) of patients; no NHANES controls were available for comparison for ferritin. ConclusionMicronutrient deficiencies remain common in adults with CD despite increased nonclassic presentation. This study provides support for micronutrient assessment at the time of CD diagnosis.

Metabolic Alterations in Celiac Disease Occurring after Following a Gluten-Free Diet

Background and Aim: Many investigations have demonstrated that changes in body weight are frequent in patients with coeliac disease (CD) after a gluten-free diet (GFD); conversely data on the metabolic syndrome (MS) and hepatic steatosis (HS) are still rare. The aim is to evaluate the prevalence of MS and HS in patients with CD, before and after a GFD. Methods: One hundred eighty-five coeliac adult patients were enrolled in the study. Diagnosis of MS was made according to the current international criteria including waist circumference (WC), hypertension, reduction of high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, and hyperglycemia. Body mass index (BMI), hypercholesterolemia, and HS were also assessed. Results: CD patients showed an increased risk of developing both MS and HS after following a GFD. MS was reported in 3.24% of the cases at the time of CD diagnosis and in 14.59% after GFD (p < 0.0001). HS was reported in 1.7% at the time of diagnosis and in 11.1% after GFD (p < 0.0001). With regard to metabolic sub-categories, the prevalence of the increase in WC, hypertension, reduction of HDL cholesterol, hyperglycemia, hypercholesterolemia, and BMI > 25 was significantly higher after GFD compared to baseline at CD diagnosis. Conclusion: In CD patients, following a GFD maybe can contribute to the development of MS and HS. Patients should be informed about this possible risk.

Can Serum Mean Platelet Volume be Used as an Inflammatory Marker in Patients with Celiac Disease?

Background and Aims: Mean platelet volume has been studied as a simple inflammatory marker in several diseases. Some studies have reported that mean platelet volume increases in myocardial infarction and cerebrovascular disease. Contrarily, it decreases in rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease. The aim of this study was to evaluate whether mean platelet volume was changed in celiac disease and whether it could be used to monitor a gluten-free diet in patients. Materials and Methods: After excluding patients with severe comorbidities and patients who did not comply with the gluten-free diet, a total of 50 patients with celiac disease (men/women: 9/41) and 50 healthy subjects (men/women: 10/40) were included in the study. The diagnosis of celiac disease was based on standard serological, endoscopic, and histological criteria. The study enrolled patients with celiac disease who recovered clinically and serologically 1 year after gluten-free diet. Complete blood count analyses were performed within 2 h after collection with the use of the Beckman coulter analyzer. Results: Mean platelet volume levels were not significantly different in the celiac disease group than that of in the control group. In the celiac disease group, the mean platelet volume levels did not change after 1 year of gluten-free diet compared with the time of celiac disease diagnosis. On the contrary, a decrease in the platelet count after gluten-free diet was detected. Conclusion: This study demonstrates that mean platelet volume is not altered in patients with celiac disease, and it also showed that mean platelet volume cannot be used as a marker for predicting dietary compliance in patients with celiac disease.

Presymptomatic Diagnosis of Celiac Disease in Predisposed Children: The Role of Gene Expression Profile.

The prevalence of celiac disease (CD) has increased significantly in recent years, and risk prediction and early diagnosis have become imperative especially in at-risk families. In a previous study, we identified individuals with CD based on the expression profile of a set of candidate genes in peripheral blood monocytes. Here we evaluated the expression of a panel of CD candidate genes in peripheral blood mononuclear cells from at-risk infants long time before any symptom or production of antibodies. We analyzed the gene expression of a set of 9 candidate genes, associated with CD, in 22 human leukocyte antigen predisposed children from at-risk families for CD, studied from birth to 6 years of age. Nine of them developed CD (patients) and 13 did not (controls). We analyzed gene expression at 3 different time points (age matched in the 2 groups): 4-19 months before diagnosis, at the time of CD diagnosis, and after at least 1 year of a gluten-free diet. At similar age points, controls were also evaluated. Three genes (KIAA, TAGAP [T-cell Activation GTPase Activating Protein], and SH2B3 [SH2B Adaptor Protein 3]) were overexpressed in patients, compared with controls, at least 9 months before CD diagnosis. At a stepwise discriminant analysis, 4 genes (RGS1 [Regulator of G-protein signaling 1], TAGAP, TNFSF14 [Tumor Necrosis Factor (Ligand) Superfamily member 14], and SH2B3) differentiate patients from controls before serum antibodies production and clinical symptoms. Multivariate equation correctly classified CD from non-CD children in 95.5% of patients. The expression of a small set of candidate genes in peripheral blood mononuclear cells can predict CD at least 9 months before the appearance of any clinical and serological signs of the disease.

Proton pump inhibitors as risk factor for metabolic syndrome and hepatic steatosis in coeliac disease patients on gluten-free diet.

Recent research has shown that patients with coeliac disease (CD) are at risk of developing metabolic syndrome (MS) and hepatic steatosis (HS) after commencing a gluten-free diet (GFD). This study aimed to evaluate the predictive factors for MS and HS in CD after 1year of GFD. All consecutive newly diagnosed CD patients were enrolled. We prospectively collected data about BMI; waist circumference; blood pressure; cholesterol; triglycerides, glucose and insulin blood levels; insulin resistance (through the homeostatic model assessment HOMA-IR) and treatment with proton pump inhibitors (PPI). Diagnosis of MS was made in accordance with current guidelines and HS was diagnosed by ultrasonography. The prevalence of MS and HS was re-assessed after 1year of GFD. A logistic regression analysis was performed to identify risk factors for MS and HS occurrence after 1year of GFD. Of 301 patients with newly diagnosed CD, 4.3% met criteria for diagnosis of MS and 25.9% presented with HS at the time of CD diagnosis; 99 subjects (32.8%) had long-term exposure to PPI during the study period. After 1year, 72 (23.9%) patients had developed MS (4.3 vs 23.9%; p<0.001, OR 6.9) and 112 (37.2%) had developed HS (25.9 vs 37.2%; p<0.01, OR 1.69). At multivariate analysis, high BMI at diagnosis (OR 10.8; p<0.001) and PPI exposure (OR 22.9; p<0.001) were the only factors associated with the occurrence of MS; HOMA-IR (OR 9.7; p<0.001) and PPI exposure (OR 9.2; p<0.001) were the only factors associated with the occurrence of HS. PPI exposure adds further risk of occurrence of MS and HS for patients with CD on GFD. The use of PPI in patients with CD on GFD should be limited to strict indications.

FRAX Score Can Be Used to Avoid Superfluous DXA Scans in Detecting Osteoporosis in Celiac Disease: Accuracy of the FRAX Score in Celiac Patients

The Fracture Risk Assessment (FRAX) tool has been developed to estimate patients' 10-yr probability of fracture, thus establishing which patients should undergo dual-energy X-ray Absorptiometry (DXA) scan. This study aimed to evaluate if the FRAX tool can replace or optimize the use of DXA scan in celiac disease (CD). We prospectively enrolled all CD patients aged over 40 yr diagnosed at our third-level unit. At time of CD diagnosis, all patients underwent FRAX score calculation for risk of major osteoporotic and hip fractures and DXA scan (used as gold standard) to assess the accuracy of the FRAX score. The FRAX score calculation was based on the following 10 variables: age (>40 yr), sex (M/F), body mass index, history of previous fracture (yes/no), parent fractured hip (yes/no), current smoking (yes/no), use of steroids (yes/no), rheumatoid arthritis (yes/no), secondary osteoporosis (yes/no), and alcohol ≥3 units/d (yes/no). DXA assessment was performed within 1 week from FRAX calculation. The FRAX score was dichotomized as normal or pathologic in accordance with the National Osteoporosis Guideline Group. A total of 160 CD patients were enrolled (M/F = 20/140; mean age 48.7 yr). A pathologic FRAX score was evident in 14 out of 160 patients (8.7%), whereas osteoporosis based on DXA scan was found in 10 patients (6%) (κ = 0.6); 3 patients with osteoporosis (1.9%) showed a 10-yr risk of major fracture >10% according to the National Osteoporosis Guideline Group criteria. With regard to diagnostic accuracy, the FRAX score showed sensitivity of 0%, specificity of 91%, positive predictive value of 0%, and negative predictive value of 94%. The prevalence of osteoporosis in adult CD appears to be quite low and only a small proportion of patients would require a DXA investigation. The FRAX score could be an effective tool to avoid useless DXA scans in CD patients in view of its high negative predictive value.

Celiac Disease in The Netherlands: Demographic Data of Members of the Dutch Celiac Society.

Celiac disease is an autoimmune disease induced by the intake of gluten with a female to male ratio of 2-4:1. Female predominance has not been recognized in serological mass screening studies. Limited data are available on gender and age distribution in the daily clinical practice of celiac disease. The aim of this study is to describe differences in gender and age at the time of celiac disease diagnosis in the Netherlands. Data was obtained from a prospectively maintained database of members of the Dutch Celiac Society in whom celiac disease was diagnosed between 1980 and August 2015. retrospective database study; Setting: database of members of the Dutch Celiac Society; Participants: out of the total number of 26,986 current and ex-members, the data of 7,886 members could be used for analysis. Age at celiac disease diagnosis ranged between 0 and 88 years; the minority (36%) were diagnosed in childhood. In children, the majority (52%) were diagnosed before the age of 4 years. Median age did not differ in children when compared for gender (3 years). In adults, median age differed between males (52 years, IQR 41-61) and females (44 years, IQR 32-56), p<0.001. Female to male ratio was 2.4:1. The majority of celiac disease patients are diagnosed during adulthood, with males diagnosed at an older age. Only one-third of the patients were diagnosed at childhood. Celiac disease is less frequently diagnosed in young adult males.

Prevalence of abnormal liver function tests in celiac disease and the effect of a gluten-free diet in the US population.

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. 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, χ(2), and Fischer's exact test were used for statistical analysis. 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. 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.

Incidence and distribution of coeliac disease in Campania (Italy): 2011-2013.

There exists a wide variation in the reported incidence of coeliac disease in recent decades. We aimed to evaluate the incidence rate of coeliac diagnoses performed in an Italian region, Campania, between 2011 and 2013 and its variation therein. All coeliac diagnoses made from 2011 to 2013 and registered within the Campania coeliac disease register (CeliacDB) were identified. Incidence rates were analysed by sex, age and province of residence, with a Poisson model fitted to determine incidence rate ratios. We found 2049 coeliac disease diagnoses registered in the CeliacDB between 2011 and 2013; 1441 of these patients were female (70.4%) and 1059 were aged less than 19 years (51.7%). The overall incidence of coeliac disease in Campania was 11.8 per 100,000 person-years (95% CI 11.3-12.3) during the study period, with marked variation by age [27.4 per 100,000 person-years (95% CI 25.8-29.1) in children under 19 years of age and 7.3 per 100,000 (95% CI 6.8-7.8) in adults] and sex [16.1 per 100,000 person-years in females (95% CI 15.3-16.9) and 7.2 per 100,000 person-years in males (95% CI 6.6-7.8)]. Coeliac disease incidence was roughly similar in Naples, Salerno, Caserta and Avellino, but about half in Benevento. More than 80% of our study population was diagnosed by the combination of positive antitransglutaminase IgA and Marsh 3. More than half of the patients were symptomatic at the time of coeliac disease diagnosis (39.7% had a classical presentation and 21.1% a non-classical one according to the Oslo definition). Coeliac disease incidence was roughly similar among Campania provinces, except in Benevento where it was about half, probably due to less awareness of coeliac disease in this area. The incidence of coeliac disease in Campania appears to be lower than that reported by most of the previous literature, suggesting the necessity of new coeliac awareness programmes.