Biopsy-proven Celiac Disease Research Articles

Symptom Outcomes of Celiac Disease in Those on a Gluten-free Diet.

We aimed to evaluate symptom outcomes in those on a gluten-free diet during the 5 years after diagnosis. Celiac disease is common; however, little is known about long-term symptom outcomes. We performed a retrospective chart review on individuals with celiac disease followed at a tertiary referral center between 2012 and 2018. To minimize bias, strict inclusion/exclusion criteria were utilized. Only those with definitive biopsy-proven celiac disease, on a gluten-free diet, and with systematic follow-up were included. The standardized care at this center reduced the risk that decisions on testing and follow-up visits were determined by symptom status. Summary statistics were computed and generalized linear models with a logit link were used to associate the proportion of symptomatic visits with various covariates using R statistical programming. Of the 1023 records reviewed, 212 met inclusion/exclusion criteria; 146 (69%) were female and the mean age at diagnosis was 43 (range: 11 to 84y old). During follow-up, over 50% remained symptomatic, with many having the same symptoms that prompted the diagnosis. The only predictors for remaining symptomatic were female sex and younger age at diagnosis. Abnormal serology during follow-up and small bowel normalization were not predictive. In individuals with definitive celiac disease with systematic long-term follow-up in a Celiac Clinic, roughly half remained symptomatic despite a gluten-free diet. Many suffer from the same symptoms that prompted the diagnosis of celiac disease. Small bowel healing and abnormal serology in follow-up were not predictive of remaining symptomatic. These findings stress the importance of long-term care in celiac disease.

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

Dietary adherence is not dependent on the mode of diagnosis in children with coeliac disease.

To compare the adherence to gluten-free diet between children with serology-based and biopsy-proven coeliac disease. Medical records were retrospectively reviewed in 257 Swedish children diagnosed with coeliac disease between 2012 and 2019 at a tertiary hospital. Adherence to a gluten-free diet was systematically assessed by trained dietitians at follow-up. Mixed models were used to analyse the dietary adherence by mode of diagnosis (serology-based vs. biopsy-proven). After mean 6.3 (SD 2.4) years, there was neither a difference in the dietary adherence over time depending on the mode of diagnosis (OR 0.64 [95% confidence interval (CI) 0.26, 1.60], p = 0.342), nor if coeliac disease was detected in screening studies (OR 0.74 [95% CI 0.25, 2.17], p = 0.584) or in risk-groups (OR 1.01 [95% CI 0.26, 3.91], p = 0.991) compared to clinically detected diagnosis. Non-adherence to a gluten-free diet increased with age (OR 1.19 [95% CI 1.06, 1.33], p = 0.003). There was no difference in the proportion of patients improving their dietary adherence from non-adherent to adherent over time (p = 0.322). Mode of diagnosis did not influence the dietary adherence in Swedish children with coeliac disease, although adherence to a gluten-free diet was inversely associated with increasing age.

Correlation between auto-immune diseases and type 1 diabetes mellitus in the pediatric age group in Erbil city

Background and objective: Type-1 diabetes mellitus is the most common chronic endocrine disorder of childhood and adolescence and is characterized by immune-mediated destruction of pancreatic cells, which has been proven to be correlated with and increase the risk of developing autoimmune thyroid disease, celiac disease, Addison’s disease, and further autoimmune diseases. The aim of this study is to evaluate the prevalence of autoimmune disease-related markers in type 1 diabetes mellitus in children and adolescents in Erbil city. Methods: One hundred children and adolescents with type 1 diabetes mellitus were enrolled in this cross-sectional study. Patients <1 year old were excluded from the study. Autoimmune thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) along with tissue transglutaminase (IgA and IgG) antibodies were measured with further evaluation by thyroid function test and endoscopy with biopsy (for positive serological autoantibodies level). Results: Elevated anti-thyroglobulin, anti-thyroid peroxidase, and tissue transglutaminase IgA and IgG antibodies were determined in 24.0%, 26%, 10%, and 8%, respectively. 50.0% of cases with positive anti-thyroid peroxidase antibodies had overt hypothyroidism; on the flip side, 3.8% had subclinical hypothyroidism. As well, the high level of thyroid autoantibodies was significantly correlated to the prevalence of overt hypothyroidism (P <0.001). Nine of the patients with positive tissue transglutaminase antibodies were verified to have biopsy-proven celiac disease. Conclusion: Children and adolescents with type 1 diabetes mellitus are at risk of developing positive antithyroid and celiac-related autoantibodies, so they are at risk of progressing to autoimmune thyroid and celiac diseases.

Prevalence and Predictive Factors for Celiac Disease in Children With Type 1 Diabetes: Whom and When to Screen? A Nationwide Longitudinal Cohort Study of Swedish Children.

To examine the prevalence and predictive factors for celiac disease (CD) after a diagnosis of type 1 diabetes (T1D) in children and adolescents, to improve the current screening guidelines. The association between sex, age at T1D diagnosis, HLA, and diabetes autoantibodies, and a diagnosis of CD was examined in 5,295 children with T1D from the Better Diabetes Diagnosis study in Sweden. The prevalence of biopsy-proven CD was 9.8%, of which 58.2% already had a CD diagnosis before or at T1D onset. Almost all, 95.9%, were diagnosed with CD within 5 years after the T1D diagnosis. Younger age at the T1D diagnosis and being homozygote for DQ2 increased the risk of CD after T1D, but neither sex nor diabetes-related autoantibodies were associated with the risk. Age at and time after diabetes diagnosis should be considered in screening guidelines for CD in children with T1D.

Accuracy of the No-Biopsy Approach for the Diagnosis of Celiac Disease in Adults: A Systematic Review and Meta-Analysis

Background & AimsCurrent international guidelines recommend duodenal biopsies to confirm the diagnosis of coeliac disease in adult patients. However, growing evidence suggests that IgA anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict coeliac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of coeliac disease in adults. MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected coeliac disease. We used a bivariate random-effects model to calculate the summary estimates of sensitivity, specificity, positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value (PPV) of the no-biopsy approach across different pre-test probabilities of coeliac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812. ResultsA total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven coeliac disease in the included studies was 62% (95% CI, 40% - 83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24% - 40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42% - 60%), and the summary specificity was 100% (95% CI, 98% - 100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 – 0.89). The PPV of the no-biopsy approach to identify patients with coeliac disease was 65%, 88%, 95%, and 99% if coeliac disease prevalence was 1%, 4%, 10% and 40%, respectively. Between-study heterogeneity was moderate (I2 =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only one study had a low risk of bias across all domains. ConclusionThe results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pre-test probability of coeliac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.

Pathological Manifestations of Gluten-Related Neuro-Psychiatric Disorders and the Impact of Gluten-Free Diet in a Pediatric Age Group: A Systematic Review.

Gluten, as a term, causes unease amonga vast majority of the population. The reason is the body's inability to process gluten, causing various pathological manifestations. While celiac disease is predominantly a gastrointestinal disease, it also has various extra-intestinal manifestations. Many children receive diagnoses of idiopathic neuropsychiatric symptoms such as epilepsy, attention-deficit hyperactivity disorder (ADHD), restless leg syndrome (RLS), and peripheral neuropathy without ever finding the root cause. A majority of these cases may be associated with celiac disease if only their antibody titers and other appropriate investigations were conducted. The treatment of these manifestations may be eliminated or at least controllable with dietary modification to a gluten-free diet (GFD). In this paper, we will discuss the pathology of celiac disease and the impact of GFD on the neuropsychiatric aspects of this disease, which is of higher prevalence in the pediatric population. A comprehensive literature search was conducted in prominent databases, namely PubMed and Google Scholar, to include studies that provided individual-level data on the neuropathological manifestations and the impact of a GFD on extra-intestinal manifestations of celiac disease. The research protocol was registered in the PROSPERO database (International Prospective Register of Systematic Reviews) with the registration ID: CRD42023415100. Based on the inclusion and exclusion criteria, we included prospective studies, observational studies, and case reports on pediatric patients with biopsy-proven celiac disease, serologically positive celiac disease, celiac disease with neuropsychiatric manifestations, and studies reporting the impact of GFD. After a rigorous quality assessment to remove the risk of bias, we finally included 20 studies to be discussed. In 6 (30%) studies, patients with neuropsychiatric manifestations had positive serology findings and a relatively higher grade of biopsy results. Seven studies discussed the positive impact of GFD. Five of these seven studies reported statistically significant results (p ≤ 0.001).Our study suggests that gluten plays a role in the severity of neuropsychiatric manifestations of celiac disease. Considering the results of our study, we can see that GFD does impact the prognosis of the disease. Neuropsychiatric findings without gastrointestinal manifestations are more common in the pediatric age group. We have clear evidence that several neurological conditions (neuropathy, ADHD, epilepsy, and RLS) have not only a significant association with gluten but can also potentially benefit from GFD. Thus, screening, with a combination of serological, biopsy, and imaging techniques, must be adapted into the guidelines for early detection and induction of GFD. Furthermore, studies should aim at introducing GFD in the pediatric population as a mode of primary prevention. In conclusion, our review underscores the importance of gluten while dealing with idiopathic neurological conditions in children and hopes to shed light on this commonly misdiagnosed and easily manageable disease.

A dietitian-led coeliac service helps to identify and reduce involuntary gluten ingestion with subsequent reduction in the frequency of repeat endoscopies.

Dietitian-led coeliac clinics have the potential to be a cost-effective way of monitoring patients living with coeliac disease (CD). The aim of this service evaluation was to explore the impact of a dietitian-led coeliac clinic on gluten-free diet (GFD) adherence and the frequency of endoscopies with repeat duodenal biopsies. Adults with biopsy-proven CD were transferred to a new dietitian-led coeliac clinic where data were collected from medical records and analysed using SPSS. GFD adherence was assessed by a specialist dietitian, specialist nurse, consultant gastroenterologists and a validated GFD adherence questionnaire. Repeat duodenal biopsy findings were compared with the most recent dietitian GFD adherence assessment. Project and ethics approval was granted by the hospital trust and affiliated university. Data from 170 patients (White: 51%, South Asian: 45%) are presented, with most being 35-64 years old (61%). Specialist dietitian assessments identified 67 (39%) of patients were adhering to the GFD, whereas prior gastroenterologist or coeliac nurse assessments identified 122 (72%) (p < 0.001) and the validated GFD adherence questionnaire identified 97 (57%) (p < 0.001). Dietitian assessments identified involuntary gluten consumption in 39/104 (38%) of those who self-reported GFD adherence, consequently avoiding the need for nine endoscopies with repeat duodenal biopsies once patients had received dietary education from the dietitian. On follow-up, within the dietitian-led coeliac clinic, significantly fewer patients consumed gluten involuntarily (14%, p < 0.001). In addition, a reduction in voluntary gluten consumption was observed from three to five to one to two times per month (p < 0.001) in 66 patients. The dietitian-led coeliac clinic helped to identify involuntary gluten ingestion, avoid repeat endoscopies with duodenal biopsies and was associated with significantly improved GFD adherence.

The effect of gluten-free diet on mean platelet volume levels as a short-term follow up biomarker in biopsy proven celiac disease patients and its comparison with IgA-tissue transglutaminase antibody levels

Background: Celiac disease is an autoimmune disease for which there is a known environmental trigger i.e., gluten. Adherence to gluten-free diet is the mainstay of treatment. Methods: This observational prospective study was conducted in the Department of Paediatrics, SP Medical College, Bikaner between August 2020 to August 2021. Newly diagnosed celiac disease patients below 14 years of age were included in the study excluding patients with any associated co-morbid conditions like Diabetes, Hypertension and Hypothyroidism. IgA-tTG titre and complete blood counts were performed at the time of diagnosis, and repeated after 3 months of strict gluten-free diet. The collected data were coded, tabulated and analysed. P values &lt; 0.05 were statistically significant. Results: The mean IgA-tTG decreased from 116.28 at the time of diagnosis to 50.98 after 3 months of the gluten-free diet (p = &lt;0.001). Also, the mean MPV decreased from 9.58 to 9.19 and the change was statistically significant (p = 0.032). When two biomarkers i.e., MPV and IgA-tTG were compared as being better biomarkers for the gluten-free diet, a weak positive correlation was observed but was not statistically significant (p = 0.212). Conclusions: This study showed that Mean Platelet Volume (MPV) levels can be used as a short-term biomarker to check adherence to the gluten-free diet.

Persistent villous atrophy predicts development of complications and mortality in adult patients with coeliac disease: a multicentre longitudinal cohort study and development of a score to identify high-risk patients

ObjectivePersistent villous atrophy (pVA) in coeliac disease (CD) despite a gluten-free diet (GFD) has unclear meaning. We aimed to (i) study the relationship between pVA and long-term outcomes and (ii)...

No Increased Risk of Cardiac Birth Defects in Infants of Mothers With Celiac Disease: A Population and Sibling Comparison.

Several earlier studies have indicated an increased risk of cardiac birth defects among infants born to mothers with celiac disease (CeD). Through linking nationwide Swedish health care registries, we aimed to investigate maternal CeD and risk of any or cardiac birth defects in their offspring. We performed a retrospective cohort study of infants born between 2002 and 2016 to women with biopsy-proven CeD (villous atrophy, Marsh III) matched to infants born to nonceliac women from the general population. Conditional logistic regression with odds ratios (OR) and their 95% confidence intervals (CI) was used to determine the association between maternal CeD and birth defects. To minimize the impact of intrafamilial confounding, we also compared infants born to mothers with CeD with infants born to their nonaffected sisters. A total of 6,990 infants were born to mothers with diagnosed CeD compared with 34,643 infants born to reference mothers. Any birth defect was seen in 234 (33 per 1,000 infants) and 1,244 (36/1,000) reference infants corresponding to an OR of 0.93 (95% CI 0.81-1.08). Cardiac birth defects were seen in 113 (16/1,000) vs 569 (16/1,000) infants (OR 0.98, 95% CI 0.80-1.20). Similar OR for any and cardiac birth defects were also seen in sibling comparisons. We found no statistically significant risk of any or cardiac birth defects in infants born to mothers with diagnosed CeD compared with the general population and to their nonaffected sisters.

Maladaptive Food Attitudes and Behaviors in Individuals with Celiac Disease and Their Association with Quality of Life.

The only treatment for celiac disease (CeD) is strict lifelong adherence to a gluten-free diet (GFD). In some individuals the demands of a GFD may contribute to maladaptive eating attitudes and behaviors that impair quality of life (QOL). The Celiac Disease Food Attitudes and Behaviors (CD-FAB) is an easily administered and scored 11-item tool querying potentially maladaptive food attitudes and behaviors resulting from beliefs around gluten exposures and food safety. To assess the usefulness of the CD-FAB in establishing the presence of maladaptive food attitudes and behaviors among adults with CeD and to explore the relationship between these attitudes and behaviors and other factors including QOL, anxiety, depression, CeD symptoms and personality traits. The study is a cross-sectional pilot of 50 adults (mean age 29.6years) with biopsy-proven CeD who followed a GFD for at least one year and had no self-reported eating disorder diagnosis. High scores on the CD-FAB tool suggest higher disordered eating attitudes and beliefs. Compared to lower scores (mean 20.2), higher (worse) CD-FAB scores (mean 54.5) were positively associated with recency of diagnosis, number of CeD-related gastrointestinal symptoms, and the personality trait of neuroticism. Higher CD-FAB scores were statistically and clinically significantly associated with diminished QOL (p < 0.001). The relationship with anxiety and depression was less clear but trended in the expected direction. The CD-FAB may be a useful tool for dietitians who wish to monitor maladaptive food attitudes and behaviors among their CeD patients, especially in the first-year post-diagnosis.

Increased Risk of Hospitalization in Celiac Disease With COVID-19 Infection Is Mitigated by Vaccination

We sought to describe clinical characteristics of celiac disease (CD) patients infected with coronavirus disease 2019 (COVID-19) and estimate hospitalization risk, intensive care unit (ICU) requirement, mortality, and thrombosis, and the impact of vaccination on these outcomes. We performed a single-center, retrospective cohort study comparing biopsy-proven CD patients with a matched sample of non-CD (referent) patients diagnosed with COVID-19 between March 2020 and January 2022. Matching ensured 2 referent patients for every 1 CD patient by age, sex, ethnicity, and COVID-19 diagnosis date. We also adjusted for general and celiac-specific comorbidity. The primary outcome was hospitalization. Secondary outcomes included ICU requirement, mortality, and thrombosis. We also compared these outcomes between vaccinated and unvaccinated individuals. We included 330 patients: 110 with CD (mean age 48 years, 83% female) and 220 matched referents. Hospitalization occurred in 27 CD patients (24%) and 25 referent patients (11%) (hazard ratio, 2.10; 95% confidence interval, 1.21-3.65; P= .007). Vaccination was associated with significantly decreased risk of hospitalization (hazard ratio, 0.53; 95% confidence interval, 0.31-0.93; P= .026). Four unvaccinated CD patients and 2 unvaccinated referent patients required ICU. No mortality occurred among CD patients, and 2 referent patients died. No thrombosis occurred in either group. CD patients with COVID-19 have a higher risk of hospitalization compared with non-CD referents. This risk is mitigated by vaccination in CD patients as it is in non-CD referents. ICU requirement occurred only in unvaccinated CD patients, and no CD patient died. Vaccination against COVID-19 should be strongly recommended in patients with CD as it is for non-CD patients in the general population.

Obsessive-Compulsive Symptomatology and Disgust Propensity in Disordered Eating Behaviors of Adolescents with Celiac Disease.

Considering the importance of underlying psychopathological mechanisms that mediate maladaptive eating behaviors in celiac disease (CD) in the determination of cognitive-behavioral therapeutic approaches, we investigated the impact of obsessive-compulsive symptomatology and disgust propensity on disordered eating attitudes (DEA) and poor gluten-free diet (GFD) compliance in adolescents with CD. Adolescents with biopsy-proven CD (n = 148, aged 12-18years) were compared with age- and sex-matched controls (n = 104) in terms of eating attitudes/behaviors, obsessive-compulsive symptoms, and disgust propensity, as well as depression and anxiety to rule out depression- and anxiety-related covariates. The clinical implications associated with poor GFD compliance were determined using between-subgroup analysis. Multivariate linear regression and multiple logistic regression were used to identify predictors of DEA and GFD noncompliance, respectively. In adolescents with CD, DEA was remarkably associated with obsessive-compulsive symptom severity and disgust propensity, especially in contamination and core disgust sub-dimensions. Obsessionality and disgust propensity were independent predictors of DEA, of which the obsessive-compulsive symptom severity was the most decisive predictor of DEA. Higher DEA severity and lower body mass index were independent predictors of poor GFD compliance. Higher obsessionality, accompanied by disgust-related evaluative conditioning processes, may contribute to constructing a cognitive network consisting of hypervigilance and catastrophic interpretations towards benign somatic stimulations, food-related preoccupations, and avoidant behaviors in the disordered eating of adolescents with CD. The reciprocal relationship between lifelong GFD and DEA, mediated by obsessionality and disgust propensity, was supported by current findings that could guide clinicians in the management of maladaptive eating behaviors in adolescents with CD.

A Clinical Investigation on ADHD-Traits in Childhood Celiac Disease

Objective: There are no definitive results about either the presence of exact comorbidity between celiac disease (CD) and attention-deficit/hyperactivity disorders (ADHD) or etiology. We intend to screen ADHD-related cognitive and behavioral traits in children with biopsy-proven CD and investigate the possible association of these traits with certain vitamin levels, body-mass index, and gluten-free diet (GFD) compliance. Method: A total of 85 children with biopsy-proven CD (the ages of 8–18 years) were compared with age and sex-matched 72 healthy controls in terms of demographics, psychiatric symptoms, certain vitamin levels, and anthropometric measurements. Results: ADHD-like cognitive issues, such as inattention and learning difficulties, as well as psychosomatic symptoms and poor prosocial behavior, were all associated with GFD noncompliance in childhood CD. Conclusion: Untreated CD may predispose to ADHD-resembling symptoms. Physicians should be aware of the probability of ADHD misdiagnosing due to ADHD-resembling cognitive and behavioral traits in untreated CD.

Perceived barriers to gluten-free diet adherence by people with celiac disease in Greece.

In people with celiac disease (CD), many factors affect adherence to a gluten-free diet (GFD), and these may well differ among countries. In Greece, such data for the adult population are lacking. Thus, the present study aimed to explore the perceived barriers to compliance with a GFD that are faced by people with CD living in Greece, also taking into account the impact of the COVID-19 pandemic. Nineteen adults (14 females) with biopsy-proven CD, mean age 39±9 years and median time on GFD 7 (Q1-Q3: 4-10) years, participated in 4 focus groups, conducted through a video conference platform during the period October 2020 to March 2021. Data analysis followed the qualitative research methodology. Eating outside the home was reported as the domain where most difficulties were faced: these were related to a lack of confidence in finding safe gluten-free food and to the lack of social awareness about CD/GFD. All participants highlighted the high cost of gluten-free products, which was mostly managed by receiving state financial support. Regarding healthcare, the vast majority of participants reported little contact with dietitians and no follow up. The COVID-19 pandemic eased the burden of eating out, as staying at home and allocating more time to cooking was experienced as a positive effect, although the shift to online food retailing impacted food variability. The main impediment to GFD adherence seems to stem from low social awareness, while the involvement of dietitians in the healthcare of people with CD warrants further investigation.

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.

Anemia Etiology and the Response to a Gluten-Free Diet in Untreated Patients With Celiac Disease: A 2-Year Follow-Up.

Anemia and micronutrient deficiencies are common in newly diagnosed patients with celiac disease (CeD). We aim to determine the prevalence and etiology of anemia in a cohort of patients with CeD in the United States and examine the effect of a gluten-free diet (GFD) on the laboratory parameters related to anemia in CeD. We analyzed a prospectively collected cohort of adults with biopsy-proven CeD followed in a specialized CeD center between January 2000 and June 2016. We used the level of hemoglobin (Hb) and micronutrients suggested by the World Health Organization to establish the diagnosis of anemia or deficiencies. Demographic data and laboratory parameters related to anemia and micronutrients were recorded at the time of diagnosis and on a GFD. A celiac expert nutritionist or gastroenterologist evaluated all patients. In 572 patients with laboratory evaluation before starting a GFD, approximately 25% presented with anemia at the time of diagnosis of CeD. Iron deficiency was present in 50.8% of the cohort and in 78.8% of the patients with anemia. Within the anemic population, 84.4% of female patients as compared with 58.3% of male patients ( P = 0.02) showed iron deficiency. Folate deficiency (23.2%), vitamin B12 deficiency (11%), and anemia of chronic diseases (7.8%) were also part of both sexes' anemia etiology. Of the initially anemic patients, 81% and 89% normalized their Hb levels within 1 year and 2 years of beginning a GFD, respectively. All patients received appropriate supplementation when needed. Approximately 25% of individuals have anemia at CeD diagnosis. The anemia etiology included iron deficiency, vitamin deficiencies, and anemia of chronic diseases. Most of the patients will normalize their Hb levels and the anemia laboratory parameters 1 year after starting a strict GFD.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.

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.