Human leukocyte antigen DQ2/8 prevalence in non-celiac patients with gastrointestinal diseases

AIM: To investigate the prevalence of human leukocyte antigen (HLA) DQ2/8 alleles in Southern Italians with liver and gastrointestinal (GI) diseases outside of celiac disease. METHODS: HLA DQ2/8 status was assessed in 443 patients from three ambulatory gastroenterology clinics in Southern Italy (University of Federico Ⅱ, Naples, Loreto Crispi Hospital, Ruggi D'Aragona Hospital, Salerno). Patients were grouped based on disease status [pre-post transplant liver disease, esophageal/gastric organic and functional diseases, irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD)] and DQ2/8 alleles, which correspond to a celiac disease genetic risk gradient. Subject allele frequencies were compared to healthy Italian controls. RESULTS: One hundred and ninety-six out of four hundred and forty-three (44.2%) subjects, median age 56 years and 42.6% female, were DQ2/8 positive. When stratifying by disease we found that 86/188 (45.7%) patients with liver disease were HLA DQ2/8 positive, 39/73 (53.4%) with functional upper GI diseases and 19/41 (46.3%) with organic upper GI diseases were positive. Furthermore, 38/105 (36.2%) patients with IBS and 14/36 (38.9%) with IBD were HLA DQ2/8 positive (P = 0.21). Compared to healthy controls those with functional upper GI diseases disorders had a 1.8 times higher odds of DQ2/8 positivity. Those with liver disease had 1.3 times the odds, albeit not statistically significant, ofDQ2/8 positivity. Both those with IBS and IBD had a lower odds of DQ2/8 positivity compared to healthy controls. CONCLUSION: The proportion of individuals HLA DQ2/8 positive is higher in those with liver/upper functional GI disease and lower in IBS/IBD as compared to general population estimates.

Recommendations to quantify villous atrophy in video capsule endoscopy images of celiac disease patients

AIM To quantify the presence of villous atrophy in endoscopic images for improved automation.METHODS There are two main categories of quantitative descriptors helpful to detect villous atrophy:(1) Statistical and(2) Syntactic. Statistical descriptors measure the small intestinal substrate in endoscope-acquired images based on mathematical methods. Texture is the most commonly used statistical descriptor to quantify villous atrophy. Syntactic descriptors comprise a syntax, or set of rules, for analyzing and parsing the substrate into a set of objects with boundaries. The syntax is designed to identify and distinguish three-dimensional structures based on their shape.RESULTS The variance texture statistical descriptor is useful to describe the average variability in image gray level representing villous atrophy, but does not determine the range in variability and the spatial relationships between regions. Improved textural descriptors will incorporate these factors, so that areas with variability gradients and regions that are orientation dependent can be distinguished. The protrusion syntactic descriptor is useful to detect three-dimensional architectural components, but is limited to identifying objects of a certain shape. Improvement in this descriptor will require incorporating flexibility to the prototypical template, so that protrusions of any shape can be detected, measured, and distinguished.CONCLUSION Improved quantitative descriptors of villous atrophy are being developed, which will be useful in detecting subtle, varying patterns of villous atrophy in the small intestinal mucosa of suspected and known celiac disease patients.

Quantitative image analysis of celiac disease

We outline the use of quantitative techniques that are currently used for analysis of celiac disease.Image processing techniques can be useful to statistically analyze the pixular data of endoscopic images that is acquired with standard or videocapsule endoscopy.It is shown how current techniques have evolved to become more useful for gastroenterologists who seek to understand celiac disease and to screen for it in suspected patients.New directions for focus in the development of methodology for diagnosis and treatment of this disease are suggested.It is evident that there are yet broad areas where there is potential to expand the use of quantitative techniques for improved analysis in suspected or known celiac disease patients.

Use of shape-from-shading to characterize mucosal topography in celiac disease videocapsule images

AIM To use a computerized shape-from-shading technique to characterize the topography of the small intestinal mucosa.METHODS Videoclips comprised of 100-200 images each were obtained from the distal duodenum in 8 celiac and 8 control patients.Images with high texture were selected from each videoclip and projected from two to three dimensions by using grayscale pixel brightness as the Z-axis spatial variable.The resulting images for celiac patients were then ordered using the Marsh score to estimate the degree of villous atrophy,and compared with control data.RESULTS Topographic changes in celiac patient three-dimensional constructs were often more variable as compared to controls.The mean absolute derivative in elevation was 2.34 ± 0.35 brightness units for celiacs vs 1.95 ± 0.28 for controls(P = 0.014).The standard deviation of the derivative in elevation was 4.87 ± 0.35 brightness units for celiacs vs 4.47 ± 0.36 for controls(P = 0.023).Celiac patients with Marsh ⅢC villous atrophy tended to have the largest topographic changes.Plotted in two dimensions,celiac data could be separated from controls with 80% sensitivity and specificity.CONCLUSION Use of shape-from-shading to construct three-dimensional projections approximating the actual spatial geometry of the small intestinal substrate is useful to observe features not readily apparent in two-dimensional videocapsule images.This method represents a potentially helpful adjunct to detect areas of pathology during videocapsule analysis.

Cardiovascular involvement in celiac disease

Celiac disease(CD) is an autoimmune response to ingestion of gluten protein, which is found in wheat, rye, and barley grains, and results in both small intestinal manifestations, including villous atrophy, as well as systemic manifestations. The main treatment for the disease is a gluten-free diet(GFD), which typically results in the restoration of the small intestinal villi, and restoration of other affected organ systems, to their normal functioning. In an increasing number of recently published studies, there has been great interest in the occurrence of alterations in the cardiovascular system in untreated CD. Herein, published studies in which CD and cardiovascular terms appear in the title of the study were reviewed. The publications were categorized into one of several types:(1) articles(including cohort and case-control studies);(2) reviews and meta-analyses;(3) case studies(one to three patient reports);(4) letters;(5) editorials; and(6) abstracts(used when no full-length work had been published). The studies were subdivided as either heart or vascular studies, and were further characterized by the particular condition that was evident in conjunction with CD. Publication information was determined using the Google Scholar search tool. For each publication, its type and year of publication were tabulated. Salient information from each article was then compiled. It was determined that there has been a sharp increase in the number of CD-cardiovascular studies since 2000. Most of the publications are either of the type "article" or "case study". The largest number of documents published concerned CD in conjunction with cardiomyopathy(33 studies), and there have also been substantial numbers of studies published on CD and thrombosis(27), cardiovascular risk(17), atherosclerosis(13), stroke(12), arterial function(11), and ischemic heart disease(11). Based on the published research, it can be concluded that many types of cardiovascular issues can occur in untreated CD patients, but that most tend to resolve on a GFD, often in conjunction with the healing of small intestinal villous atrophy. However, in some cases the alterations are irreversible, underscoring the need for CD screening and treatment when cardiovascular issues arise of unknown etiology.

Non-responsive celiac disease in children on a gluten free diet

BACKGROUND Non-responsive celiac disease(NRCD) is defined as the persistence of symptoms in individuals with celiac disease(CeD) despite being on a gluten-free diet(GFD). There is scant literature about NRCD in the pediatric population.AIM To determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODS Retrospective cohort study performed at Boston Children’s Hospital(BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh Ⅲ histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo(responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTS Six hundred and sixteen children were included. Ninety-one(15%) met criteria for NRCD. Most were female(77%). Abdominal pain [odds ratio(OR) 1.8 95% confidence interval(CI) 1.1-2.9], constipation(OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension(OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure(30%) and constipation(20%) being the most common causes. Other causes for NRCD included lactose intolerance(9%), gastroesophageal reflux(8%), functional abdominal pain(7%), irritable bowel syndrome(3%), depression/anxiety(3%), eosinophilic esophagitis(2%), food allergy(1%), eating disorder(1%), gastric ulcer with Helicobacter pylori(1%), lymphocytic colitis(1%), aerophagia(1%) and undetermined(13%). 64% of children with NRCD improved on follow-up.CONCLUSION NRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.

Seroprevalence of celiac disease among United Arab Emirates healthy adult nationals: A gender disparity

AIM:To determine celiac disease(CD)prevalence and associated manifestations or risk factors in healthy adult Emiratis.METHODS:It is a cross-sectional prospective study,recruiting 1197(573 women and 624 men)healthy Emiratis between September 2007 and April 2008among those who went to Al Ain Hospital to undertake the prenuptial examination.Test for anti-tissue transglutaminase(tTG)IgA antibodies was used for CD diagnosis.Subjects with positive results in the anti tTG antibodies assay were also tested for anti-endomysial(EMA)IgA antibodies.A structured interview was used to collect basic demographic and clinical recall data including:information on name,contact address,age,gender,education status,previous diagnosis of CD,diagnosis of CD in 1st degree relatives and history of"chronic diarrhea,anemia,headache,hepatitis,diabetes,tumor,and thyroid disorder".RESULTS:Fourteen blood samples(1.17%;14/1197)were seropositive for CD.The latent CD seropositive patients were 13 women and 1 man and therefore the seroprevalence of CD was 1:86(14/1197)for adult Emiratis:1:44(13/573)for women and 1:624 for men.Binary logistic regression revealed that history of chronic anemia(crude OR=7.09;95%CI:2.32-21.61;P=0.003)and being a woman(OR=14.46;95%CI:1.89-110.91;P=0.001)were associated with CD seropositivity.Whereas,the thyroid disorder showed a positive association with CD seropositivity that approach statistical significance(OR=11.30;95%CI:1.32-96.95;P=0.09)and therefore was included in the multiple logistic regression analysis,which showed that CD seropositivity is independently associated only with history of chronic anemia(OR=4.58;95%CI:1.45-14.48;P=0.01)and being a woman person(OR=10.47;95%CI:1.33-82.14;P=0.026).CONCLUSION:Compared to men the CD seroprevalence among women was remarkably higher.The CD association with women and chronic anemia is of importance from a public health perspective.

Understanding celiac disease monitoring patterns and outcomes after diagnosis:A multinational,retrospective chart review study

BACKGROUND Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease.AIM To understand patterns of follow-up and management of patients with celiac disease,and to characterize symptoms and villous atrophy after diagnosis.METHODS A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease.Three gastroenterology referral centers,with substantial expertise in celiac disease,participated in the United Kingdom,United States,and Norway.Demographic and clinical data were collected from medical charts.Descriptive analyses were conducted on patients with biopsyconfirmed celiac disease,diagnosed between 2008 and 2012,with at least one follow-up visit before December 31,2017.Patient demographic and clinical characteristics,biopsy/serology tests and results,symptoms,and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period(i.e.,before the study end date of December 31,2017).RESULTS A total of 300 patients were included in this study[72%female;mean age at diagnosis:38.9 years,standard deviation(SD)17.2].Patients were followed-up for a mean of 29.9 mo(SD 22.1)and there were,on average,three follow-up visits per patient during the study period.Over two-thirds(68.4%)of patients were recorded as having ongoing gastrointestinal symptoms and 11.0%had ongoing symptoms and enteropathy during follow-up.Approximately 80%of patients were referred to a dietician at least once during the follow-up period.Half(50.0%)of the patients underwent at least one follow-up duodenal biopsy and 36.6%had continued villous atrophy.Patterns of monitoring varied between sites.Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration.CONCLUSION This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

Risk perception and knowledge of COVID-19 in patients with celiac disease

BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019(COVID-19)in patients with celiac disease(CeD)is similar to that of the general population.However,how patients with CeD perceive their COVID-19 risk may differ from their actual risk.AIM To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception.METHODS We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics,diet,COVID-19 testing,and risk perceptions of COVID-19 in patients with CeD.Participants were recruited through various celiac associations,clinic visits,and social media.Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population.Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception,such as age,sex,adherence to a gluten-free diet(GFD),and comorbidities such as cardiac conditions,respiratory conditions,and diabetes.Data was presented as adjusted odds ratios(aORs)RESULTS A total of 10737 participants with CeD completed the survey.From them,6019(56.1%)patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population.A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD(56.1%vs 26.7%,P<0.0001).Consequently,34.8%reported taking extra COVID-19 precautions as a result of their CeD.Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members(49.5%vs 57.4%,P<0.0001).Older age(aOR:0.99;95%CI:0.99 to 0.99,P<0.001),male sex(aOR:0.84;95%CI:0.76 to 0.93,P=0.001),and strict adherence to a GFD(aOR:0.89;95%CI:0.82 to 0.96,P=0.007)were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk(aOR:1.38;95%CI:1.22 to 1.54,P<0.001).CONCLUSION Overall,high levels of risk perceptions,such as those found in patients with CeD,may increase an individual’s pandemic-related stress and contribute to negative mental health consequences.Therefore,it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community.Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.

Anti-microbial antibodies in celiac disease:Trick or treat?

AIM:To determine the prevalence of a new set of anti-glycan and anti-outer membrane protein (anti-OMP) antibodies in a Hungarian cohort of adult Celiac disease (CD) patients.METHODS:190 consecutive CD patients [M/F:71/119, age:39.9 (SD:14.1) years], 100 healthy, and 48 gastrointestinal controls were tested for glycan anti-Saccharomyces cerevisiae (gASCA), anti-laminaribioside (ALCA), anti-chitobioside, anti-mannobioside, anti-OMP antibodies and major NOD2/CARD15 mutations. Thirty out of 82 CD patients enrolled at the time of diagnosis were re-evaluated for the same antibodies after longstanding gluten-free diet (GFD).RESULTS: 65.9% of the CD patients were positive for at least one of the tested antibodies at the time of the diagnosis. Except anti-OMP and ALCA, anti-microbial antibodies were exclusively seen in untreated CD; however, the overall sensitivity was low. Any glycan positivity (LR+:3.13;95% CI:2.08-4.73) was associated with an increased likelihood ratio for diagnosing CD. Significant correlation was found between the levels of anti-glycan and anti-endomysial or anti-transglutaminase antibodies. Anti-glycan positivity was lost after longstanding GFD. Anti-glycan antibody titers were associated with symptoms at presentation, but not the presence of NOD2/CARD15 mutations. Patients with severe malabsorption more frequently had multiple antibodies at diagnosis (P=0.019).CONCLUSION: The presence of anti-glycan antibodies in CD seems to be secondary to the impaired small bowel mucosa which can lead to increased antigen presentation. Furthermore, anti-glycan positivity may be considered an additional marker of CD and dietary adherence.

肠易激综合征的饮食疗法对低可发酵性短链碳水化合物饮食的高度期望

肠易激综合征（irritablebowelsyndrome，IBS）是常见的消化系统疾病，影响全球人口的10％左右。IBS没有明确的生物标志物及根治方法，近年来引入各种治疗药物，包括抗生素（治疗假定的小肠细菌过度生长）和通过液体分泌及肠神经系统调节肠道动力的药物。虽然，这些药物有其优点，但近年来最受患者欢迎的治疗方法为饮食疗法。

乳糜泻及非乳糜泻性麦胶敏感症

乳糜泻是具有基因特异性的个体，因摄入麦胶而激发的多系统免疫异常。乳糜泻的患病率在近几十年来逐渐增加，目前在西方人群中已达1％。尽管与饮食卫生相关的多种环境因素值得怀疑，但其发病增加的原因并不明确。乳糜泻的发病机制涉及与饮食中的麦胶成分相关的原发性及适应性的免疫反应。该病的，临床表现多种多样，包括胃肠道症状、代谢性骨病、生育不能，以及其他多种多样的表现。虽然无麦胶食物对大多数患者的治疗有效，但这样的饮食令人烦恼并影响生活质量。因此。在疾病的不同阶段也需要非饮食疗法。本综述也总结了非乳糜泻性麦胶敏感症。对这一临床亚型的发病机制仍然缺乏了解，但这一现象使得无麦胶食品在人群中的应用受到重视。