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Objective: In recent years, patients with celiac disease (CeD) have been reported to have a high prevalence of fatty liver and metabolic syndrome. We conducted a systematic review and meta-analysis to assess the prevalence of fatty liver and metabolic syndrome in patients with CeD and effect of gluten-free diet in them., Methods: The PubMed, Embase and the Cochrane Library databases were searched for original studies upto November 18, 2022. We included full-text articles published in the English language after 1990 that used well-defined criteria for CeD, fatty liver and metabolic syndrome. A random effects model was used to calculate pooled prevalence., Results: Of 350 studies identified, 11 studies (n = 2578) were included in the analysis. On analysis of both cross-sectional and longitudinal studies, pooled prevalence of fatty liver and metabolic syndrome in treatment-naïve patients with CeD were 18.2% (95% CI 8.3-30.8%, n = 1237) and 4.3% (95% CI 2.4-6.7, n = 1239) and in those on GFD of varying duration was 28.2% (95% CI 20.7-36.4%, n = 1368) and 21.3% (95% CI 11.7-32.9%, n = 2193), respectively. There was no difference in the prevalence of fatty liver and metabolic syndrome between low- or high-income group countries., Conclusions: Patients with CeD have a high prevalence of fatty liver and metabolic syndrome which increases further with the initiation of GFD. Patients with CeD should thus be screened and monitored for development of fatty liver and metabolic syndrome. They should be counselled appropriately regarding their diet and inclusion of physical activity in their lifestyle., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aim: Abnormalities in the reproductive functions are often ignored while evaluating a patient with celiac disease (CeD). We evaluated the entire reproductive functions in female patients with CeD., Methods: In a case control study between 2020 and 2021 using detailed questionnaire, we evaluated reproductive functions (age at menarche, menstrual pattern, fertility, pregnancy outcome and menopause) in biopsy-proven female patients with CeD of age >10 years. The questionnaire was administered either in person or telephonically. Age-matched healthy female controls (twice the number) were also recruited., Results: Of 1086 CeD patients, 470 were females and 288 were included. As compared with controls (n = 586), females with CeD had higher age at menarche (14.6 ± 2.0 vs 13.6 ± 1.5 years; P = 0.001), delayed menarche (30.8% vs 11.4%; P = 0.001), abnormal menstrual pattern (39.7% vs 25.8%; P < 0.001), involuntary delay in conception at > 1 year (33.8% vs 11.8%; P = 0.01), current infertility rate (10.5% vs 5.2%;P = 0.028), and poorer overall pregnancy outcomes (abortion [23.5% vs 12.8%; P = 0.001], pre-term birth [16.3% vs 3.7%; P = 0.001])., Conclusions: Either one or more aspect of reproductive functions and pregnancy outcome is affected adversely in three-fourth female patients with CeD., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objectives: Nutritional quality of gluten-free (GF) food products is very important, as patients with celiac disease consume these products for lifelong. There is paucity of data on the nutritional content and cost of GF food products compared with their gluten-containing (GC) counterparts from India (Asia)., Design: After a detailed market survey, packaged and labeled GF food products (n=485) and their packaged GC counterparts (n=790) from the supermarkets of Delhi (India) and e-commerce websites were included. Nutritional content and cost/100 g food (in US dollars) were calculated using the information on food label., Results: Gluten-free food products were 232% (range: 118% to 376%) more expensive than their GC counterparts. Energy content of all GF food products was similar to their GC counterparts, except cereal-based snacks (GF: 445 kcal vs. GC: 510 kcal, p<0.001). The protein content was significantly lower in GF pasta and macaroni products (single-grain: GF: 6.5 g vs. GC:11. 5 g, p-0.002; multigrain: GF:7.6 g vs. GC:11.5 g, p-0.027), cereal flours (single-grain: GF: 7.6 g vs. GC: 12.3 g, p<0.001; multigrain: GF:10.9 g vs. GC: 14.1 g, p-0.009) and nutritional bars (GF: 21.81 g vs. GC:26 g, p-0.028) than their GC counterparts. Similarly, the dietary-fiber content of GF pasta and macaroni products, cereal flours, cereal premix and nutritional bars of GF foods was significantly lower than their GC counterparts. Gluten-free bread and confectionary items, biscuits and cookies and snacks had higher total fats and trans-fat content than their GC counterparts. Gluten-free cereal-based snacks had higher sodium content than their GC counterparts (GF: 820 mg vs. GC:670 mg; p<0.001)., Conclusion: GF foods are significantly more expensive, contain less protein and dietary fiber and higher fat, trans-fat and sodium than their GC counterparts. Strategies must be developed to reduce the cost and improve the nutritional profile of GF foods., (© 2024. Indian Society of Gastroenterology.)

Objectives: We hypothesized that crypt failure in the small bowel results in villous flattening in patients with celiac disease (CeD). We investigated whether alterations in the stem cell niche (ISC) are responsible for this phenomenon., Materials and Methods: We included 92 duodenal (D2/3) biopsies from treatment-naive patients of CeD and 37 controls. All underwent screening for serum anti-tissue transglutaminase and endoscopic upper small bowel biopsy. Immunohistochemical markers were used to investigate ISC niche alterations, including LGR5 for crypt basal cells (CBC), Bmi1 for position 4+ cells, β-Defensin for Paneth cells, R-spondin1 as WNT activator, transcription factor-4 as WNT transcription factor, BMP receptor1A as WNT inhibitor, fibronectin-1 as periepithelial stromal cell marker, H2AX as apoptosis marker, and Ki67 as proliferation marker. We also analyzed IgA anti-tTG2 antibody deposits by using dual-color immunofluorescence staining., Results: We found that in biopsies from patients with treatment-naive CeD with modified Marsh grade 3a-3c changes, the epithelial H2AX apoptotic index was upregulated than in controls. LGR5+ crypt basal cells were upregulated in all modified Marsh grades compared to controls. However, the Ki67 proliferation index, expressions of WNT-activator RSPO1, and position-4 cell marker Bmi1 did not significantly alter in patients' biopsies as compared to controls ( P = 0.001). We also observed depletion of pericrypt stromal fibronectin-1 in patients with CeD compared to controls. In addition, we identified IgA anti-TG2 antibody deposits in pericrypt stroma., Conclusions: Our data suggests that ISC niche failure is a plausible hypothesis for villous flattening in patients with CeD, resulting from pericrypt IgA anti-TG2 antibody complex-mediated stromal depletion., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Introduction: While lifelong and strict adherence to gluten-free diet (GFD) is essential for the successful treatment of celiac disease (CeD), only 30-50% of patients are able to maintain a good adherence to GFD. We determined factors influencing the adherence to GFD at various ecological levels including intra-personal, inter-personal, organizational, community and system-based levels in adult patients with CeD., Methods: A questionnaire to assess the adherence was developed and it was administered in the CeD clinic to patients with CeD on GFD for >1 year. Adherence to GFD was assessed in a subset of patients (n = 320) using Celiac Disease Adherence Test (CDAT)., Results: Overall, 978 patients [median age: 29 years; females: 592] with CeD on GFD were recruited. They reported many barriers to adherence to GFD including intra-personal barriers such as lack of knowledge about GFD (19%), inadequate financial resources (27.2%) and lack of self-motivation/confidence (55.3%); inter-personal barriers such as intake of gluten-containing food upon forceful insistence of friends/family (23.4%); organizational barriers such as high cost (70.8%) and non-availability of GF-food products (48.6%); community-based barriers like consumption of gluten-containing food at religious occasions/festivals (11.1%) and social occasions (27.2%); and system-based barriers such as non-referral to dietitian for counseling (21.9%). As per CDAT, 204 (63.7%), 73(22.8%) and 43(13.4%) patients had good, average, and poor adherence to GFD, respectively. On multivariable analysis, occasional consumption of gluten, non-availability of GF-food while dining out and coercing by family and friends for consumption of GC-food were found to have highest odds for poor adherence to GFD., Conclusions: Non-referral to a dietitian for counseling, irregular follow-up visits, unavailability of flour mill, non-supportive family/friends, high cost and limited availability of GF-food are the most common barriers to adherence to GFD. There is a need to create infrastructure and develop strategies to overcome these diverse barriers at various levels of ecosystem and thereby facilitate better adherence to GFD., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: It is challenging to make diagnosis of non-celiac gluten sensitivity/non-celiac wheat sensitivity (NCGS/NCWS) in clinical practice, since there is no biomarker and diagnosis is based on response to gluten-free-diet (GFD). We used anti-gliadin antibody (AGA) for screening patients with IBS for gluten-sensitivity., Methods: 492 Adult-patients with IBS underwent screening for celiac disease and gluten-sensitivity using IgA anti-tissue transglutaminase antibody and IgA-AGA and IgG-AGA, respectively. Patients with positive AGA (IgA and/or IgG) were invited to follow GFD, those willing were put on GFD for 6-weeks. Responsive patients were given gluten re-challenge. Diagnosis of NCGS was confirmed if they had recurrence of symptoms., Results: Of 492 patients with IBS, AGA was positive in 61(12.4 %), hence suspected to have gluten-sensitivity. Of 31 who agreed to participate and followed GFD for 6-weeks, 17 (54.8 %) had complete (>30 % improvement) and 10(32.2 %) had partial (>20 % improvement) response. All 17 complete-responders were given gluten re-challenge for 6-weeks, symptoms recurred in all and hence were confirmed to have NCGS/NCWS. Significant decrease in AGA levels occurred almost in all GFD-responders., Conclusions: 12.4 % IBS patients have biological evidence of gluten/wheat-sensitivity. Almost 87 % patients with IBS having AGA responded to GFD. The value of AGA may further be explored as a biomarker for screening for the presence of NCGS, before recommending this test for the clinical practice., Competing Interests: Conflict of Interest All authors declare no potential conflict of interest., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aim: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD., Methods: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2., Results: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2., Conclusions: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD., Methods: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification., Results: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD., Conclusions: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Immunoproliferative small intestinal disease (IPSID) is an uncommon disease of the small intestine. There is a similarity in the clinical presentations of enteropathic diseases, including celiac disease, tropical sprue, IPSID, and Whipple's disease. A differentiation between them is based on the use of a highly specific serological test for celiac disease and specific histological characteristics. We found that IgA-anti-tissue transglutaminase antibody (IgA-tTG Ab) is falsely elevated in a subset of patients with IPSID. The levels of IgA-tTG Ab fall with the treatment of IPSID. The healthcare professional should be aware of the conditions that lead to a false-positive anti-tTG Ab. Intestinal mucosal biopsies even in the presence of anti-tTG Ab should be done in endemic regions as they provide an opportunity for making a diagnosis of alternative and uncommon diseases before the diagnosis of celiac disease., (© 2023. Indian Society of Gastroenterology.)

Introduction: A subset of patients with celiac disease (CeD) has liver involvement in the form of hypertransaminasemia, liver cirrhosis, and autoimmune hepatitis. We conducted a systematic review with meta-analyses to determine the pooled prevalence of CeD in patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia., Methods: We searched PubMed and EMBASE up to January 2022. Cross-sectional, case-control, and prospective cohort studies performing serological tests and/or intestinal biopsy for CeD on patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia were included to calculate pooled estimates of seroprevalence and the prevalence of biopsy-confirmed CeD in these 4 groups., Results: Of 6,871 articles screened, 20 articles were included finally in 3 meta-analyses for cryptogenic cirrhosis, all-cause cirrhosis, and cryptogenic hypertransaminasemia. For the all-cause hypertransaminasemia group, a qualitative review of 4 studies was conducted instead of a meta-analysis due to significant differences in studies. The pooled prevalence (95% confidence interval) of biopsy-confirmed CeD in cryptogenic cirrhosis was 4.6% (2.2%-7.5%) while the pooled prevalence of biopsy-confirmed CeD in all-cause cirrhosis was 0.8% (0%-3.4%). The pooled prevalence of biopsy-confirmed CeD in cryptogenic hypertransaminasemia was 5.7% (3.2%-8.8%)., Discussion: Nearly 1 in 20 patients each with cryptogenic cirrhosis and cryptogenic hypertransaminasemia have CeD; hence, they should both be considered high-risk groups for CeD. While the prevalence of CeD in those with all-cause cirrhosis is similar to that in general population, it may be worth screening them for CeD because liver pathology has the potential for reversal in them., (Copyright © 2023 by The American College of Gastroenterology.)

Background: The pattern of practice regarding the diagnosis, dietary counselling and follow-up of patients with celiac disease (CeD) varies between practice to practice., Methods: A web-based questionnaire based on review of literature, group discussions and expert group meetings was developed to understand the practice of CeD in India. The questionnaire was administered through social media (WhatsApp) to 18 Indian celiac support groups comprising 2980 patients with CeD., Results: Overall, 970 (32.5%) patients responded to the questionnaire (median age: 21 years; females 63.9%). While 679 (71.1%) patients were diagnosed based on a combination of serology and biopsy, 214 (22.4%) were diagnosed based on serology alone. After diagnosis, 875 (91%) patients were counselled initially by physician and only 585 (61%) were referred to a dietician for dietary counselling. In a majority of cases, the time spent by doctors and dietitians during first counselling was between 10 and 20 minutes only. After first counselling, 191 (20%) and 355 (37.3%) patients did not re-visit the physician and the dietitian, respectively. Among those who followed up, structured follow-up was conducted in only 515 (53.8%) patients. Overall, 232 (24.3%) patients were self-monitoring their serological parameters, while 495 (51.8%) patients did not receive a formal assessment of dietary adherence during follow-up., Conclusion: The practice of diagnosis, dietary counselling and follow-up of patients with CeD in India is not as per standard guidelines. Most of the patients are not referred to a dietitian. There is a need for reinforcement of guidelines for proper care and management of patients with CeD., (© 2023. Indian Society of Gastroenterology.)

Celiac disease (CeD) is an immune-mediated chronic disorder triggered by the ingestion of wheat gluten in genetically predisposed individuals. Gluten is a major food ingredient, infamously containing proline and glutamine-rich domains that are highly resistant to digestion by mammalian proteolytic enzymes. Thus, adhering to a gluten-free diet (GFD) is the only known treatment for CeD, albeit with many complications. Therefore, any therapy that eliminates the gluten immunogenic part before it reaches the small intestine is highly desirable. Probiotic therapy containing gluten-degrading bacteria (GDB) and their protease enzymes are possibly new approaches to treating CeD. Our study aimed to identify novel GDB from the duodenal biopsy of the first-degree relative (FDR) subjects (relatives of diseased individuals who are healthy but susceptible to celiac disease) with the potential to reduce gluten immunogenicity. Using the gluten agar plate technique, bacterial strains Brevibacterium casei NAB46 and Staphylococcus arlettae R2AA77 displaying glutenase activity were screened, identified, and characterized. Whole-genome sequencing found gluten-degrading prolyl endopeptidase (PEP) in the B. casei NAB46 genome and glutamyl endopeptidase (GEP) in the S. arlettae R2AA77 genome. Partially purified PEP has a specific activity of 1.15 U/mg, while GEP has a specific activity of 0.84 U/mg, which are, respectively, 6- and 9-fold times higher after concentrating the enzymes. Our results showed that these enzymes could hydrolyse immunotoxic gliadin peptides recognized in western blot using an anti-gliadin antibody. Additionally, a docking model was proposed for representative gliadin peptide PQPQLPYPQPQLP in the active site of the enzymes, where the residues of the N-terminal peptide extensively interact with the catalytic domain of the enzymes. These bacteria and their associated glutenase enzymes efficiently neutralize gliadin immunogenic epitopes, opening possibilities for their application as a dietary supplement in treating CeD patients.

Background: The causal association between IgA nephropathy (IgAN) and celiac disease (CeD) is based on their clinical coexistence. In this prospective study, we screened patients with IgAN for CeD and explored the utility of analysis of IgA anti-TG2 antibody deposits, for establishing a causal association., Methods: Biopsy-proven patients of IgAN were screened for serum IgA anti-tissue transglutaminase antibody (IgA anti-tTG Ab) titer and thereafter were invited to undergo endoscopic duodenal biopsy. Corresponding duodenal and kidney biopsies were subjected to IgA anti-TG2 antibody colocalization study using dual-color immunohistochemistry and immunofluorescence techniques. Additionally, kidney biopsies from 105 patients with IgAN who did not give consent for serology analysis, 30 non-IgA nephropathies, and 10 normal controls were also included. Dual-color-stained slides were interpreted based on stain distribution and intensity scores, and Pearson's index >0.3-1 on confocal imaging was considered significant., Results: Of a cohort of 151 patients with IgAN, 32 consented to undergo sero-screening and 5 of them had high serum anti-tTG Ab titer. Two out of the latter consented to endoscopic duodenal biopsies, in whom modified Marsh grade 3b changes were identified. Strong IgA anti-TG2 antibody deposits were noted in the kidney and duodenal biopsies of these patients. One patient out of non-consenting 105 patients with IgAN and 3 out of 30 patients with other non-IgA nephropathies also showed IgA anti-TG2 deposits. None of the healthy kidney tissues showed IgA anti-TG2 Ab deposits., Conclusions: Co-localized IgA anti-TG2 deposits in the kidney biopsies in patients with IgAN help to establish a pathogenic link with CeD. A small proportion of patients with IgAN have associated CeD., Competing Interests: None

Background: IgA anti-tissue transglutaminase-2 antibody (anti-TG2Ab) deposits in intestinal and extraintestinal organs have been used to link the respective pathological changes in these organs with celiac disease (CeD)., Aims: To know if parts of intestine other than the duodenum, such as esophagus, stomach, and colon, have any pathology related to potential CeD or have mucosal IgA anti-TG2 Ab deposits., Settings and Design: A prospective case-control study conducted from April 2018 to December 2019., Materials and Methods: Nine patients with potential CeD and 27 age- and gender-matched patients with irritable bowel syndrome were recruited as cases and controls, respectively. Mucosal biopsies were collected from esophagus, stomach, duodenum, and rectosigmoid regions, histological changes were evaluated, and IgA anti-TG2 Ab deposits were analyzed in these regions by two-color immunohistochemical staining., Statistics: Data were analyzed using statistical software Stata 14.0., Results: No distinct difference in mucosal lymphocytosis were identified between biopsies of patients with potential CeD and controls at the following sites: esophagus (11.1% vs 0%, P = 0.079), stomach (14.3% vs 7.7%, P = 0.590), and rectum (20% vs 0%, P = 0.067). Co-localized IgA anti-TG2Ab deposits were observed more in potential CeD than in controls at esophagus 22.2% (2/9) vs 0%, P = 0.012; stomach 66.7% (6/9) vs 11.5% (3/26), P < 0.001; and duodenum 66.7% (6/9) vs 0%, P < 0.001 but not at rectum 0% (0/4) vs 0% (0/25)., Conclusion: Although histological changes are not distinct, a subset of subjects with potential CeD has pan-intestinal involvement other than in the duodenum., Competing Interests: None

Celiac disease (CeD) is a chronic gluten-induced enteropathy with plethoric manifestations. The typical manifestations of CeD such as chronic diarrhea and malabsorption are widely recognized, however, many patients have atypical manifestations like iron deficiency anemia, idiopathic short stature, hypertransaminesemia or infertility, etc. These patients often present to the primary care physicians and/or non-gastrointestinal specialties. However, due to a lack of awareness among the healthcare professionals about the various atypical manifestations, many patients are not screened for CeD. In this review, we have summarized the available literature about the prevalence of CeD in various gastrointestinal (chronic diarrhea) and non-gastrointestinal conditions (iron deficiency anemia, short stature, cryptogenic hypertransaminesemia, cryptogenic cirrhosis or idiopathic ataxia etc. ) where the diagnosis of CeD should be con-sidered. In addition, we also discuss special scenarios where screening for CeD should be considered even in absence of symptoms such as patients with type 1 diabetes, Down's syndrome, and first-degree relatives of patients with CeD. Further, we discuss the diagnostic performance and limitations of various screening tests for CeD such as IgA anti-tissue transglutaminase antibodies, anti-endomysial antibodies and anti-deamidated gliadin antibodies. Based on the current recommendations, we propose a diagnostic algorithm for patients with suspected CeD., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: While celiac disease (CeD) is considered to affect primarily the small intestine, pathological changes in other parts of the gastrointestinal tract (GIT) are also known to occur. IgA anti-tissue transglutaminase-2 antibody (anti-TG2 Ab) deposits at the site of involvement is one of the methods to establish CeD-related tissue pathology., Aims: To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies., Methods: Forty-two treatment-naive patients with CeD and 45 patients with irritable bowel syndrome were included as cases and controls, respectively. Mucosal biopsies were collected from the esophagus, stomach, duodenum, and rectosigmoid regions at baseline from cases and controls, and additionally after 6-months of gluten-free diet in cases. All biopsies were evaluated for histological changes and subjected to dual-color immunohistochemical staining for identifying IgA anti-TG2 Ab deposits., Results: Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P < 0.01) and lymphocytic colitis (17.4% vs. 0%, P < 0.05) than that in controls. IgA anti-TG2 Ab deposits were observed in significantly more numbers in esophagus (30.9% vs. 6%, P < 0.001), stomach (62.2% vs. 9.3%, P < 0.01), duodenum (88.5% vs. 0%, P < 0.001) and rectum (17.4% vs. 0%, P < 0.05) than that in controls. There was a decline, but not statistically significant, in severity of lymphocytosis and intensity of IgA anti-TG2 Ab deposits in follow-up biopsies., Conclusion: Significantly higher number of patients with CeD had evidence of lymphocytic infiltration and IgA anti-TG2 deposits along GIT suggesting that CeD affects other parts of GIT., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with celiac disease (CeD) can commonly present with symptoms of dyspepsia. We conducted a systematic review and meta-analysis of the present literature to assess the prevalence of CeD in patients diagnosed with dyspepsia., Methods: We searched MEDLINE and EMBASE databases for the keywords: celiac disease, coeliac disease, anti-gliadin, tissue transglutaminase antibody, anti-endomysial antibody, dyspepsia and functional gastrointestinal disorder. All the studies published from January 1991 till May 2021 were included. Diagnosis of CeD was based on the European Society of Pediatric Gastroenterology, Hepatology and Nutrition guidelines. A random-effects model was used to pool the data., Results: Twenty-one studies screening 10,275 patients with dyspepsia were included. The pooled seroprevalence of CeD based on a positive anti-tissue transglutaminase antibody and/or anti-endomysial antibody was 4.8% (95% CI [2.8, 6.7%], I 2  = 87.7%). The pooled biopsy-confirmed CeD prevalence was 1.5% (95% CI [1.0, 1.9%]; I 2  = 59.8%) in these patients. Both seroprevalence (Odds ratio: 1.8; 95% CI [0.8, 4.0%]; I 2  = 0%) and prevalence of biopsy-confirmed CeD (Odds ratio: 1.4; 95% CI [0.8, 2.4]; I 2  = 0%) were not higher in patients with dyspepsia compared to controls. There was a moderate risk of selection bias and significant heterogeneity in the pooled results., Conclusions: The pooled prevalence of CeD in patients with dyspepsia was 1.5% and it was not significantly higher than the general population. These results do not support screening of patients with dyspepsia for CeD., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coeliac disease is an immune-mediated disease caused by ingestion of gluten in genetically susceptible individuals. Coeliac disease has been thought to affect mainly people of European origin but subsequently many studies revealed that it affects people living in North America, Oceania, South America, Asia as well as Africa. The global pooled seroprevalence and prevalence of biopsy-confirmed coeliac disease are 1.4% and 0.7% respectively. The pooled incidence rates in women and men are 17.4 (95% CI: 13.7-21.1) and 7.8 (95% CI: 6.3-9.2) per 100 000 person-years respectively. The systematic reviews, based on many population-based data, suggest that both the prevalence and the incidence of coeliac disease has increased over past three decades, which may be attributable not only to an increase in the detection rate (improvement in diagnostic tests, simplification of diagnostic criteria and increase in awareness about the disease) but also because of modernisation and globalisation related changes in the dietary practices including increase in the use of convenience food and dietary gluten. In addition to genetic factors, while there are many environmental risk factors, including age at the first introduction of gluten, breastfeeding, caesarean section, exposure to antibiotics and gut microbiome; the amount of gluten ingestion during early part of life, however, has been shown to increase the risk of coeliac disease, and this is relevant from the point of view of primary prevention. In this review, we have reviewed and summarised the literature, up till year 2021, related to the global and continent-wise epidemiology and risk factors associated with coeliac disease., (© 2022 John Wiley & Sons Ltd.)

Aims: Despite clinical evidence of liver involvement in patients with coeliac disease (CeD), there is a lack of a method to prove this association., Methods: Of 146 treatment-naive patients with CeD, 26 had liver dysfunction. Liver biopsies and corresponding small intestinal biopsies were obtained from these 26 patients. Multicolour immunohistochemical and immunofluorescence confocal microscopic studies were performed on paraffin-embedded tissue to detect the IgA/anti-TG2 deposits. Follow-up liver biopsies were taken after a gluten-free diet., Results: Twenty-six out of the 146 patients (17.8%) with suspected coeliac-associated liver disease on histological examination revealed irregular sinusoidal dilatation in 15 (57.6%), steatohepatitis in 4 (15.3%), non-specific chronic hepatitis in 3 (11.5%), autoimmune hepatitis in 2 (7.6%) biopsies, including cirrhosis in one of them, irregular perisinusoidal fibrosis and changes of non-cirrhotic portal fibrosis in one biopsy each (3.8%). IgA/anti-tTG deposits were observed in 22 (84.6%) liver biopsies by dual immunohistochemistry technique, and in 24 (92.3%) by confocal immunofluorescence technique and in all corresponding duodenal biopsies (100%). Overall, IgA/anti-tTG deposits showed 100% sensitivity, 77% specificity and 85% positive predictive value for establishing an association of extraintestinal pathology and CeD using archived tissues. Follow-up liver biopsies could be obtained in five patients; four of them showed not only resolution of the histological lesions but disappearance of IgA/anti-tTG co-localisation., Conclusions: Data of the present study adds to the body of evidence that liver lesions in patients with CeD are disease related and may have been caused by a similar pathogenic mechanism that causes intestinal changes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Growth retardation is an important feature of celiac disease (CeD) that can lead to the failure of attainment of potential adult height. There is lack of data on the spectrum of height in treatment-naïve patients with CeD, with normal expected height at one end and short stature at the other., Methods: We performed a retrospective analysis of a prospectively maintained database at our center, including a total of 583 treatment-naïve patients with CeD: 419 adults (183 [43.7%] males) and 164 adolescents (12-18 years) (72 [43.9%] males). The details extracted from the database included demographic details, height, weight, body mass index, clinical symptoms, biochemical parameters, anti-tissue transglutaminase antibody anti-tTG Ab) titer, and the severity of villous abnormalities (as per modified Marsh grade). The data from Indian National Family Health Survey-4 were used as comparators., Results: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While mean height of men with CeD was similar, women were taller than population controls. While a higher proportion of men with CeD had short stature as compared to the controls (32.2% vs. 20%, p<0.001), a lower proportion of women with CeD had short stature (9.7% vs. 18.9%, p<0.001). Higher proportion of adolescents with CeD had short stature compared to adults (57.9% vs. 19.6%, p<0.001). On multivariate analysis, adulthood was found to be associated with a lower prevalence of short stature., Conclusions: Overall, 19.6% of adults and 57.9% of adolescents with CeD had short stature. While the mean height of adult men with CeD was not significantly different from the population controls, women were taller. Adolescents with CeD were significantly shorter than their peers., (© 2021. Indian Society of Gastroenterology.)

Background: While the small intestine is the main site of disease, many other organs are affected by celiac disease (CeD). Dental enamel defects (DED) are common in patients with CeD, and these are one of the indicators of CeD, even when no other symptom of CeD is present. Data on dental and oral cavity manifestations in Asian patients with CeD are scanty. The purpose of the current study was to evaluate dental and oral manifestations in Asian patients with CeD., Methods: We recruited 118 patients with biopsy-confirmed CeD (36 treatment naïve and 82 on follow-up for at least 1 year on gluten-free diet [GFD]) and 40 controls. Diagnosis was made as per the standard criteria. Oral and dental manifestations were evaluated by a dental surgeon. The DED were evaluated according to Aine's criteria., Results: Overall higher number of patients with CeD (66.9%), both treatment naïve (69.4%) and those on GFD (65.8%) had DED in comparison to controls (20%) (odds ratio, 8.1, 95% confidence interval [CI] 3.4-19.2; p<0.001). Specific/bilaterally symmetrical DED were significantly higher in patients with CeD than controls. Recurrent aphthous ulcers were also significantly higher in patients with CeD. Approximately 80.6% and 63.4% treatment-naïve patients and those on GFD, respectively reported dry mouth sensation, which was significantly higher than the controls., Conclusion: Almost two-third of patients with CeD had DED. Physicians and dietitians caring for patients with CeD should be trained in identification of DED and other oral manifestations of CeD., (© 2021. Indian Society of Gastroenterology.)

Objective: Gluten-free (GF) diet is the only reliable treatment for patients with celiac disease (CeD), but data on the extent of gluten contamination in GF food available in India is scanty. We evaluated gluten content in labeled, imported, and non-labeled GF food products currently available in the Indian market., Methods: Overall, 794 processed and commercially available packaged GF products (labeled GF (n = 360), imported GF (n = 80), and non-labeled/naturally GF (n = 354)) were collected from supermarkets of National Capital Region of India. Those unavailable in stores were purchased from e-commerce sites or directly from the manufacturers. Gluten level in them was determined by Ridascreen Gliadin sandwich R5 enzyme-linked immunosorbent assay (R-Biopharm AG, Germany). As per Codex Alimentarius and Food Safety and Standard Authority of India, "gluten free" labeled products must not contain > 20 mg/kg of gluten., Results: Overall, 10.1% of 794 GF products including 38 (10.8%) of 360 labeled and 42 (11.8%) of 354 non-labeled/naturally GF food products had gluten content > 20 mg/kg (range: 24.43-355 and 23.2-463.8 mg/kg, respectively). None of the imported GF products had gluten more than the recommended limits. Contaminated products most commonly belonged to cereal and their products (flours, coarse grains, pasta/macaroni, snack foods) pulse flours, spices, and bakery items., Conclusions: A substantial proportion (10.1%) of GF food products (both labeled and non-labeled) available in India have gluten content greater than the prescribed limits of <20 mg/kg. Physicians, dietitians, support group, and patients with CeD should be made aware of this fact and regulatory bodies should ensure quality assurance., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field., Competing Interests: None

Background and Aim: Short stature is a common extraintestinal manifestation of celiac disease (CeD). We conducted a systematic review and meta-analysis to assess the global prevalence of CeD in patients presenting with short stature., Methods: We searched Medline and EMBASE databases for the keywords "celiac disease, coeliac disease, anti-gliadin, tissue transglutaminase antibody, anti-endomysial antibody, short stature and growth retardation." All the studies published from January 1991 to May 2020 were included. Patients without any prior evaluation for short stature were classified as all-cause short stature, while prior evaluated patients, where no cause was found for short stature, were classified as idiopathic short stature. The diagnosis of CeD was based on the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines. A random-effects model was used to pool the data., Results: Seventeen studies screening 3759 patients (1582 with all-cause short stature and 2177 with idiopathic short stature) were included. The pooled seroprevalence of CeD based on positive anti-tissue transglutaminase antibody and anti-endomysial antibody was 11.2% (95% CI 4.0-21.2%; I 2  = 86%) and 9.7% (95% CI 2.7-20.2%; I 2  = 95%) for all-cause and idiopathic short stature, respectively. Similarly, pooled prevalence of biopsy-confirmed CeD was 7.4% (95% CI 4.7-10.6%; I 2  = 76%) and 11.6% (95% CI 4.1-22.2%; I 2  = 97%), for all-cause and idiopathic short stature, respectively. There was an overall severe risk of selection bias and significant heterogeneity in the pooled results., Conclusions: Approximately one in 14 patients with all-cause short stature and one in nine patients with idiopathic short stature had biopsy-confirmed CeD. Therefore, evaluation for CeD may be prudent in all patients with short stature., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Alanine aminotransferase (ALT) is a cytosolic enzyme specific to hepatocytes, and its elevated level in the peripheral blood denotes liver cell injury. Detection of persistently elevated ALT levels during routine health check-up in asymptomatic or symptomatic individuals provides a window of opportunity to explore the causes of liver cell damage and for the timely institution of appropriate treatment. This was a retrospective study using a subset of the data from a previous community-based prospective study done for the estimation of the prevalence of celiac disease (CD) in India,  during which estimation of ALT levels in the blood samples of participants was also carried out. Of the 11,053 individuals (4399 [39.8%] males; mean age 37.9 ± 13.3 years) screened, 6209 consented to provide blood samples for testing for CD. Of these, assessment of serum ALT levels was done in 6083 (2235 [36.7%] males) patients. ALT was elevated above the upper limit of normal (ULN) (> 40 IU/L) in 1246 (20.5%) of the participants and > 1.5 times (> 60 IU/L) in 329 (5.4%) participants. The ALT levels were elevated more frequently in men as compared to women (29.4% vs. 15.3%, p < 0.001). There was a significant positive correlation (Pearson correlation coefficient [r] = 0.25, p < 0.0001) between ALT levels and body mass index (BMI). With increasing age, there was a significant decrease in the proportion of subjects with ALT ≥ 1.5× ULN (p < 0.001). Our results suggest that a high proportion (20.5%) of individuals otherwise considered healthy have values of ALT level in the serum above the "normal" range/cut-off suggesting likely ongoing underlying liver damage. There is a need for measures to evaluate and, if found, treat the underlying cause for the same.

Tissue transglutaminse-2 (TG2)-based immunoassays are the cornerstone of diagnosis in celiac disease (CeD), with a reported pooled sensitivity as high as 98%. 1 However, a few small, single-center studies have questioned their sensitivity in clinical practice. 2-5 Moreover, commercial kits use variable TG2 antigens, 6 with cutoffs determined by using small, poorly defined populations. Variation in diagnostic performance of anti-TG2 assays in different racial and geographic populations has not yet been studied. We compared the interassay and intra-assay variations in diagnostic performance of 4 immunoglobulin (Ig)A-anti-TG2 assays in Canadian and Indian populations., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Celiac disease (CeD) is an autoimmune enteropathy caused by gluten intake in genetically predisposed individuals. We investigated the metabolism of CeD by metabolic profiling of intestinal mucosa, blood plasma and urine using NMR spectroscopy and multivariate analysis. The metabolic profile of the small intestinal mucosa was compared between patients with CeD (n = 64) and disease controls (DCs, n = 30). The blood plasma and urinary metabolomes of CeD patients were compared with healthy controls (HCs, n = 39). Twelve metabolites (proline (Pro), arginine (Arg), glycine (Gly), histidine (His), glutamate (Glu), aspartate, tryptophan (Trp), fumarate, formate, succinate (Succ), glycerophosphocholine (GPC) and allantoin (Alln)) of intestinal mucosa differentiated CeD from controls. The metabolome of blood plasma with 18 metabolites (Pro, Arg, Gly, alanine, Glu, glutamine, glucose (Glc), lactate (Lac), acetate (Ace), acetoacetate (AcAc), β-hydroxybutyrate (β-OHB), pyruvate (Pyr), Succ, citrate (Cit), choline (Cho), creatine (Cr), phosphocreatine (PCr) and creatinine) and 9 metabolites of urine (Pro, Trp, β-OHB, Pyr, Succ, N-methylnicotinamide (NMN), aminohippurate (AHA), indoxyl sulfate (IS) and Alln) distinguished CeD from HCs. Our data demonstrated changes in nine metabolic pathways. The altered metabolites were associated with increased oxidative stress (Alln), impaired healing and repair mechanisms (Pro, Arg), compromised anti-inflammatory and cytoprotective processes (Gly, His, NMN), altered energy metabolism (Glc, Lac, β-OHB, Ace, AcAc, Pyr, Succ, Cit, Cho, Cr and PCr), impaired membrane metabolism (GPC and Cho) and intestinal dysbiosis (AHA and IS). An orthogonal partial least square discriminant analysis model provided clear differentiation between patients with CeD and controls in all three specimens. A classification model built by combining the distinguishing metabolites of blood plasma and urine samples gave an AUC of 0.99 with 97.7% sensitivity, 93.3% specificity and a predictive accuracy of 95.1%, which was higher than for the models built separately using small intestinal mucosa, blood plasma and urine. In conclusion, a panel of metabolic biomarkers in intestinal biopsies, plasma and urine samples has potential to differentiate CeD from controls and may complement traditional tests to improve the diagnosis of CeD., (© 2020 John Wiley & Sons, Ltd.)

Background and Aim: Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non-invasive biomarker(s) that can predict the presence of villous abnormalities., Methods: Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I-FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut-off values were derived, and the results were further validated in a prospective validation cohort., Results: While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n = 131) in comparison with healthy (n = 216) and disease controls (n = 133), and their levels reversed after a gluten-free diet (GFD). In the model of predicted enteropathy (n = 70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was  ≤ 30 μM/L and I-FABP levels were ≥ 1100 pg/mL, respectively. The results were validated in a prospective validation cohort (n = 104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade > 2 at calculated cut-off values of citrulline and I-FABP., Conclusions: Plasma citrulline  ≤ 30 μM/L is the most consistent, highly reproducible non-invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Strong association exists between celiac disease and autoimmune endocrinopathies such as type I diabetes and hypothyroidism; there is a lack of data on the involvement of other endocrine organs such as pituitary-gonadal axis. Furthermore, there is lack of data on the spectrum of involvement of endocrine organs varying from organ autoimmunity to subclinical and clinical disease. We evaluated consecutive treatment-naïve patients with celiac disease (CeD) for clinical and subclinical endocrinopathies., Methods: Of 154 screened, 74 treatment-naïve patients with CeD were recruited. They underwent hormonal and/or functional assessment of beta cell of pancreas, thyroid gland, pituitary-gonadal axis, and parathyroid glands., Results: Of the 74 patients with CeD, 31 (41.9%) had at least one clinical or subclinical endocrinopathy and 9 (12.2%) had multiple endocrinopathies. Most common of them were clinical or subclinical type I diabetes and autoimmune thyroid disease. Interestingly, 8 (10.8%) patients also were found to have functional hypopituitarism and 7/54 (12.9%) having isolated hypogonadotropic hypogonadism., Conclusions: Patients with CeD have high percentages of not only clinical endocrinopathy including pituitary-gonadal axis dysfunction but also subclinical endocrinopathy. Whether commencement of gluten-free diet will lead to reversal of subclinical endocrinopathies requires further follow up studies.

Aim: Patients with celiac disease (CeD) are prone to develop other autoimmune diseases such as autoimmune thyroid disease and type 1 diabetes. While 7.5% of first-degree relatives (FDRs) of patients with CeD develop CeD, it is not clear whether FDRs of patients with CeD are at higher risk of developing autoimmune thyroid disease., Methods: In this prospective case-control study, we recruited 194 FDRs (males 53.1%) of 91 patients with CeD and 140 age-matched healthy controls (males 76.4%). They were screened for CeD using anti-tissue transglutaminase antibodies (anti-tTG Ab) and thyroid disease using a symptom questionnaire, anti-thyroid peroxidase antibodies (anti-TPO) and serum thyroid-stimulating hormone (TSH). Subjects having positive anti-TPO but a normal TSH were classified as having thyroid autoimmunity and those with elevated TSH with or without positive anti-TPO Ab were classified as having autoimmune thyroid dysfunction., Results: The prevalence of thyroid autoimmunity and autoimmune thyroid dysfunction in FDRs was significantly higher than that in healthy controls (17.5% vs. 5.0%, p < 0.01; 11.8% vs. 3.5%, p < 0.01), respectively. A significantly higher number of FDRs had a positive anti-tTG Ab in comparison with controls (13.9% vs. 2.2%, p < 0.001). Amongst FDRs having thyroid autoimmunity, 44.1%, 47.0% and 8.8% were siblings, parents and children of patients with CeD, respectively. Familial clustering was seen only in 1 family., Conclusion: FDRs of patients with CeD have 3-fold higher risk of developing autoimmune thyroid disorders and associated thyroid dysfunction. Therefore, it is advisable for early screening of FDRs for CeD and associated thyroid autoimmune through screening measures.

Goals: To perform a systematic review and meta-analysis to estimate the overall diagnostic accuracy of point of care tests (POCTs) for diagnosing celiac disease (CD)., Background: Recently, POCTs for CD have been developed and are commercially available. Studies have reported significant variability in their sensitivity (70% to 100%) and specificity (85% to 100%)., Study: We searched MEDLINE, EMBASE databases, and the Cochrane library through June 2017. Positive reference test was defined as villous atrophy along with positive celiac-specific serology and/or clinical improvement after gluten-free diet. Normal duodenal biopsy was defined as negative reference test. Bivariate random-effect model was used to present the summary estimates of sensitivities and specificities along with 95% confidence regions We assessed methodologic quality using the quality assessment of diagnostic accuracy studies-2 tool., Results: The pooled sensitivity and specificity of all POCTs (based on tTG or DGP or tTG+Anti-gliadin antibodies) for diagnosing CD were 94.0% [95% confidence interval (CI), 89.9-96.5] and 94.4% (95% CI, 90.9-96.5), respectively. The pooled positive and negative likelihood ratios for POCTs were 16.7 and 0.06, respectively. The pooled sensitivity and specificity for IgA-tTG-based POCTs were 90.5% (95% CI, 82.3-95.1) and 94.8% (95% CI, 92.5-96.4), respectively., Conclusions: The pooled sensitivity and specificity of POCTs in diagnosing CD are high. POCTs may be used to screen for CD, especially in areas with limited access to laboratory-based testing. Further research assessing the diagnostic accuracy of individual POCTs and comparing it with other available POCTs is needed.

Background and Aim: While the prevalence of celiac disease (CD) is increasing globally, the prevalence of tropical sprue (TS) is declining. Still, there are certain regions in the world where both patients with CD and TS exist and differentiation between them is a challenging task. We conducted a systematic review of the literature to find out differentiating clinical, endoscopic, and histological characteristics between CD and TS., Methods: Medline, PubMed, and EMBASE databases were searched for keywords: celiac disease, coeliac, celiac, tropical sprue, sprue, clinical presentation, endoscopy, and histology. Studies published between August 1960 and January 2018 were reviewed. Out of 1063 articles available, 12 articles were included in the final analysis., Results: Between the patients with CD and TS, there was no difference in the prevalence and duration of chronic diarrhea, abdominal distension, weight loss, extent of abnormal fecal fat content, and density of intestinal inflammation. The following features were more common in CD: short stature, vomiting/dyspepsia, endoscopic scalloping/attenuation of duodenal folds, histological high modified Marsh changes, crescendo type of IELosis, surface epithelial denudation, surface mucosal flattening, thickening of subepithelial basement membrane and celiac seropositivity; while those in TS include anemia, abnormal urinary D-xylose test, endoscopic either normal duodenal folds or mild attenuation, histologically decrescendo type of IELosis, low modified Marsh changes, patchy mucosal changes, and mucosal eosinophilia., Conclusions: Both patients with CD and TS have overlapping clinical, endoscopic, and histological characteristics, and there is no single diagnostic feature for differentiating CD from TS except for celiac specific serological tests., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Celiac disease (CeD) is an autoimmune enteropathy which affects approximately 0.7% of the global population. While first-degree relatives (FDR) of patients with CeD have a 7.5% risk of developing enteropathy, many remain protected. Therefore, intestinal mucosa of FDR might have protective compensatory mechanisms against immunological injury. We have explored the protective mechanisms that may be active in intestinal mucosa of FDR., Methods: Intestinal mucosal biopsies (4-5 pieces) from treatment naïve patients with CeD (n = 12), FDR (n = 12) (anti-tTG negative) and controls (n = 12) (anti-tTG negative) were obtained from each individual and subjected to microarray analysis using HT-12-v4 Human Expression BeadChips (Illumina). Differential gene expression analysis was carried out among CeD, FDR and controls; and resulting gene lists were analyzed using gene ontology and pathway enrichment tools., Results: Patients with CeD, FDR and control groups displayed significant differential gene expression. Thirty seven genes were upregulated and 372 were downregulated in the intestinal mucosa of FDR in comparison to CeD and controls. Pseudogenes constituted about 18% (315/1751) of FDR differentially expressed genes, and formed "clusters" that associated uniquely with individual study groups. The three study groups segregated into distinct clusters in unsupervised (PCA) and supervised (random forests) modelling approaches. Pathways analysis revealed an emphasis on crypt-villous maintenance and immune regulation in the intestinal mucosa of FDR., Conclusions: Our analysis suggests that the intestinal mucosa of celiac FDR consist of a unique molecular phenotype that is distinct from CeD and controls. The transcriptomic landscape of FDR promotes maintenance of crypt-villous axis and modulation of immune mechanisms. These differences clearly demonstrate the existence of compensatory protective mechanisms in the FDR intestinal mucosa.

Tissue transglutaminase 2 enzyme plays a diverse role in intracellular and extracellular functioning. Aberrant expression of anti-TG2 antibody has recently been proposed for extraintestinal identification of celiac disease (CeD), but its utility is questionable. To examine whether anti-TG2 immunohistochemical (IHC) staining can be of diagnostic value in identifying extraintestinal involvement in CeD, tissue blocks of patients with IgA nephropathies (IgAN), minimal change disease, membranous glomerulonephritis, membrano-proliferative glomerulonephritis, normal kidney, intestinal biopsies from CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease; liver biopsies from patients with chronic hepatitis B and C, acute liver failure (ALF), and CeD-associated liver diseases were retrieved and subjected to IHC staining for anti-tissue transglutaminase 2 enzyme. H-score was calculated by multiplying the area of positivity and stain intensity. Anti-TG2 stain H-scores were almost similar in IgAN and non-IgANs (H-score 6.31±3 vs. 7.03±2.7); however, H-scores in both of these groups were significantly higher than in normal renal parenchyma (1.6±1.5). Only 6.2% patients with IgAN with anti-TG2 immunostain positivity showed a positive anti-tTG antibody serology and villous abnormalities, suggestive of CeD. Intestinal biopsies from patients with CeD, tropical sprue, nonspecific duodenitis, and inflammatory bowel disease also showed high anti-TG2 H-scores, with no statistically significant differences. Liver biopsies from patients with both ALF, as well as chronic liver diseases showed high anti-TG2 H-scores; with highest stain expression in ALF. In conclusion, IHC expression of anti-TG2 stain correlates with both acute and chronic tissue injuries, irrespective of etiology and organ involvement. It is not a reliable marker for diagnosis of CeD.

Background & Aims: Celiac disease is a major public health problem worldwide. Although initially it was reported from countries with predominant Caucasian populations, it now has been reported from other parts of the world. The exact global prevalence of celiac disease is not known. We conducted a systematic review and meta-analysis to estimate the global prevalence of celiac disease., Methods: We searched Medline, PubMed, and EMBASE for the keywords celiac disease, celiac, celiac disease, tissue transglutaminase antibody, anti-endomysium antibody, endomysial antibody, and prevalence for studies published from January 1991 through March 2016. Each article was cross-referenced with the words Asia, Europe, Africa, South America, North America, and Australia. The diagnosis of celiac disease was based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. Of 3843 articles, 96 articles were included in the final analysis., Results: The pooled global prevalence of celiac disease was 1.4% (95% confidence interval, 1.1%-1.7%) in 275,818 individuals, based on positive results from tests for anti-tissue transglutaminase and/or anti-endomysial antibodies (called seroprevalence). The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% (95% confidence interval, 0.5%-0.9%) in 138,792 individuals. The prevalence values for celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was higher in female vs male individuals (0.6% vs 0.4%; P < .001). The prevalence of celiac disease was significantly greater in children than adults (0.9% vs 0.5%; P < .001)., Conclusions: In a systematic review and meta-analysis, we found celiac disease to be reported worldwide. The prevalence of celiac disease based on serologic test results is 1.4% and based on biopsy results is 0.7%. The prevalence of celiac disease varies with sex, age, and location. There is a need for population-based prevalence studies in many countries., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Severity of villous atrophy in celiac disease (CeD) is the cumulative effect of enterocyte loss and cell regeneration. Gluten-free diet has been shown to benefit even in patients having a positive anti-tissue transglutaminase (tTG) antibody titre and mild enteropathy., Aim: We explored the balance between mucosal apoptotic enterocyte loss and cell regeneration in mild and advanced enteropathies., Methods: Duodenal biopsies from patients with mild enteropathy (Marsh grade 0 and 1) (n=26), advanced enteropathy (Marsh grade ≥2) (n=41) and control biopsies (n=12) were subjected to immunohistochemical staining for end-apoptotic markers (M30, H2AX); markers of cell death (perforin, annexin V); and cell proliferation (Ki67). Composite H-scores based on the intensity and distribution of markers were compared., Results: End-apoptotic markers and marker of cell death (perforin) were significantly up-regulated in both mild and advanced enteropathies, in comparison to controls; without any difference between mild and advanced enteropathies. Ki67 labelling index was significantly higher in crypts of mild enteropathy, in comparison to controls, suggesting maintained regenerative activity in the former., Conclusions: Even in patients with mild enteropathy, the rate of apoptosis is similar to those with advanced enteropathy. These findings suggest the necessity of reviewing the existing practice of not treating patients with mild enteropathy., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Ten to 15% of first-degree relatives (FDRs) of celiac disease (CeD) patients develop CeD. Although intestinal barrier functions (intestinal permeability) are abnormal in the subset of serology-negative FDRs, what leads to the abnormal barrier function is not known., Goals: To study the ultrastructure and functions of tight junctions in serology-negative FDRs of CeD patients., Study: The intestinal permeability was measured in 97 asymptomatic and anti-tissue transglutaminase antibody (anti-tTG Ab)-negative FDRs (using the lactulose mannitol ratio) and in 75 controls. The ultrastructure of tight junctions using transmission electron microscopy, and the expression of key tight junction proteins (claudin-2, claudin-3, occludin, JAM-A, and ZO-1) and zonulin using real-time PCR and immunohistochemistry were assessed in anti-tTG Ab-negative, HLA-DQ2/-DQ8-positive FDRs having normal villi and in disease controls. In addition, the serum zonulin level was measured in 172 anti-tTG Ab-negative FDRs and 198 controls., Results: The intestinal permeability was significantly increased in FDRs than in controls. Ultrastructural abnormalities such as dilatation of the tight junction (P=0.004) and loss of the pentalaminar structure (P=0.001) were more common in FDRs than in disease controls. There was significant underexpression of tight junction proteins ZO-1 (P=0.040) and occludin (P=0.041) in FDRs. There was no significant difference in the serum zonulin level between FDRs and controls (P=0.154)., Conclusions: Even asymptomatic, anti-tTG-Ab-negative FDRs with a normal villous histology have both ultrastructural and functional abnormalities in tight junctions. These findings are indirect evidence of the presence of tight junction abnormalities before the onset of the disease and may have therapeutic implications.

Background: Celiac disease, once thought to be uncommon in Asia, is now recognized in Asian nations as well. We investigated the prevalence of celiac disease in first-degree relatives of celiac disease patients followed in our centre., Methods: First-degree relatives were screened prospectively for celiac disease using questionnaire-based interview and anti-tissue transglutaminase antibody. Serology positive first-degree relatives underwent duodenal biopsies. Diagnosis of celiac disease was made based on positive serology and villous abnormality Marsh grade 2 or higher. Human leucocyte antigen DQ2/-DQ8 was also assessed in 127 first-degree relatives., Results: 434 first-degree relatives of 176 celiac disease patients were prospectively recruited; 282 were symptomatic (64.9%), 58 were positive for serology (13.3%). Seroprevalence was higher in female than in males (19% vs 8.5%; p=0.001) and highest in siblings (16.9%) than parents (13.6%) and children (5.9%) of celiac patients (p=0.055); 87.4% first-degree relatives were human leucocyte antigen-DQ2/-DQ8 positive. Overall prevalence of celiac disease was 10.9% amongst first-degree relatives., Conclusions: The prevalence of celiac disease in first-degree relatives of celiac disease patients was 10.9% in our cohort, and 87% had human leucocyte antigen-DQ2 or -DQ8 haplotype. All first-degree relatives of celiac disease patients should be screen for celiac disease even if asymptomatic or with atypical manifestations., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: Although celiac disease (CeD) affects 1% of people in the northern part of India, it is believed to be uncommon in the southern and northeastern parts because of significant differences in dietary pattern and ethnicity. We estimated the prevalence of CeD in these three populations. In a subset, we also investigated differences in the prevalence of HLA-DQ 2/8 allelotype and dietary grain consumption., Methods: A total of 23,331 healthy adults were sampled from three regions of India-northern (n=6207), northeastern (n=8149), and southern (n=8973)-and screened for CeD using IgA anti-tissue transglutaminase antibody. Positive tests were reconfirmed using a second ELISA. CeD was diagnosed if the second test was positive and these participants were further investigated. A subsample of participants was tested for HLA-DQ2/-DQ8 and underwent detailed dietary evaluation., Results: Age-adjusted prevalence of celiac autoantibodies was 1.23% in northern, 0.87% in northeastern, and 0.10% in southern India (P<0.0001). Prevalence of CeD and latent CeD, respectively, was 8.53/1,000 and 3.70/1,000 in northern, 4.66/1,000 and 3.92/1,000 in northeastern, and 0.11/1,000 and 1.22/1,000 in the southern part. The population prevalence of genes determining HLA-DQ2 and/or -DQ8 expression was 38.1% in northern, 31.4% in northeastern, and 36.4% in southern India. Mean daily wheat intake was highest in northern (455 g) compared with northeastern (37 g) or southern part (25 g), whereas daily rice intake showed an inverse pattern., Conclusions: CeD and latent CeD were most prevalent in northern India and were the least in southern India. The prevalence correlated with wheat intake and did not reflect differences in the genetic background.

Background: It is believed that patients with celiac disease (CeD) are likely to be underweight. Data from west suggest that 8% to 40% of them can be overweight or obese. We reviewed data on body mass index (BMI) of our patients with CeD and derived the correlations between BMI and other disease characteristics., Methods: We retrospectively studied case records of 210 adolescent and adult patients with CeD at the Celiac Disease Clinic. We classified BMI as underweight, normal weight, overweight, and obese based on the Consensus Statement for Diagnosis of Obesity, Abdominal Obesity and the Metabolic Syndrome for Asian Indians for those with age >18 years and revised Indian Association of Pediatrics BMI-for-age charts for those between 12 and 18 years., Results: Of 210 patients, 76 (36.2%) were underweight, 115 (54.8%) were normal weight, 13 (6.2%) were overweight, and 6 (2.9%) were obese. There was no difference in the proportion of underweight between male and female patients with CeD. The mean age of underweight patients was similar to those having normal or overweight. There was no difference in the mean duration of symptoms; frequencies of diarrhea, anorexia, and weakness; anemia; titer of anti-tissue transglutaminase antibody; and severity of villous atrophy in those with underweight or normal weight or overweight., Conclusions: In our practice, only one third of patients with CeD had low BMI. A diagnosis of CeD should not be excluded if patient has normal or high BMI.

Background: While adherence to gluten-free diet (GFD) is essential for effective control of celiac disease, the level of adherence to GFD may vary. We assessed the level of adherence to GFD and identified barriers to adherence in patients with celiac disease., Methods: Both treatment-naive and follow up patients with celiac disease were recruited from a celiac disease clinic. All the patients were assessed for symptom improvement using celiac symptom index (CSI), weight, and hemoglobin; adherence to GFD using detailed dietary history and food-labeled quiz questionnaire; identification of barriers to GFD using a self-administered 36-point questionnaire; and quality of life using a standard 36-item short form (SF36) questionnaire., Results: Among the patients who were already on GFD, only 53.3% maintained an excellent or good level of adherence, which increased to 92.4% at 6 months with repeated counseling. Among the treatment-naive patients, 64.8% maintained either excellent or good compliance at 1 month after first counseling, which increased to 96.3% at 6 months with repeated counseling. The most common barrier to adherence was non-availability of GFD. Certain barriers could be modified with repeated counseling and education. Response to GFD, as measured by CSI, gain in weight, and improvement in hemoglobin, was better in those having either excellent or good compliance to GFD compared to those who remained poorly adherent., Conclusions: Repeated counseling increased the level of adherence to GFD.

Objective: The clinical spectrum of celiac disease (CeD) is wide and its symptoms overlap with those of functional bowel diseases. This study aimed to investigate the relationship among gluten-related disorders, irritable bowel syndrome (IBS) and uninvestigated dyspepsia in Indian patients., Methods: Patients with IBS and uninvestigated dyspepsia (using Rome III criteria) were tested for immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG) antibody and anti-gliadin antibody (AGA). Those with positive anti-tTG antibody were evaluated for the presence of villous abnormalities. Patients who were only IgA AGA-positive were considered to have gluten sensitivity and those with positive anti-tTG antibody and villous atrophy were considered to have CeD., Results: Of 362 patients with IBS, 22 (6.1%) had positive anti-tTG antibody, among whom 3 (0.8%) had CeD and 19 had potential CeD. Of 358 patients with uninvestigated dyspepsia, 18 (5.0%) were anti-tTG antibody-positive and among them 4 (1.1%) had CeD and 14 had potential CeD. AGA was positive in 104 (28.7%) patients with IBS and 68 (19.0%) with uninvestigated dyspepsia, suggesting the presence of gluten sensitivity., Conclusion: This study highlights the relationship between IBS or dyspepsia and CeD or gluten sensitivity., (© 2015 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Abnormalities of transmembrane and cytoplasmic proteins of tight junctions (TJ) have been implicated in pathogenesis of both celiac (CeD) and Crohn's diseases (CD). Since disease pathogenesis in CeD and CD are different, we planned to study if there is any differential expression pattern of TJ marker proteins and ultrastructural changes, respectively, in duodenal villi vs crypts. Endoscopic duodenal biopsies from treatment naïve patients with CeD (n = 24), active CD (n = 28), and functional dyspepsia (as controls, n = 15), both at baseline and 6 months after treatment, were subjected to light microscopic analysis (modified Marsh grading); immune-histochemical staining and Western blot analysis to see the expression of key TJ proteins [trans-membrane proteins (claudin-2, claudin-3, claudin-4, occludin, and JAM) and cytoplasmic protein (ZO-1)]. Transmission electron microscopy and image analysis of the TJs were also performed. There was significant overexpression of claudin-2 (pore-forming) and occludin (protein maintaining cell polarity) with under-expression of claudin-3 and claudin-4 (pore-sealing proteins) in treatment naïve CeD and active CD with simultaneous alteration in ultrastructure of TJs such as loss of penta-laminar structure and TJ dilatation. Normalization of some of these TJ proteins was noted 6 months after treatment. These changes were not disease specific and were not different in duodenal villi and crypts. Overexpression of pore-forming and under-expression of pore-sealing TJ proteins lead to dilatation of TJ. These changes are neither disease specific nor site specific and the end result of mucosal inflammation.

Background and Aim: Once thought to be uncommon in Asia, coeliac disease (CD) is now being increasingly recognized in Asia–Pacific region. In many Asian nations, CD is still considered to be either nonexistent or very rare. In recognition of such heterogeneity of knowledge and awareness, the World Gastroenterology Organization and the Asian Pacific Association of Gastroenterology commissioned a working party to address the key issues in emergence of CD in Asia., Methods: A working group consisting of members from Asia–Pacific region, Europe, North America, and South America reviewed relevant existing literature with focus on those issues specific to Asia–Pacific region both in terms of what exists and what needs to be done., Results: The working group identified the gaps in epidemiology, diagnosis, and management of CD in Asian–Pacific region and recommended the following: to establish prevalence of CD across region, increase in awareness about CD among physicians and patients, and recognition of atypical manifestations of CD. The challenges such as variability in performance of serological tests, lack of population-specific cut-offs values for a positive test, need for expert dietitians for proper counseling and supervision of patients, need for gluten-free infrastructure in food supply and creation of patient advocacy organizations were also emphasized., Conclusions: Although absolute number of patients with CD at present is not very large, this number is expected to increase over the next few years or decades. It is thus appropriate that medical community across the Asia–Pacific region define extent of problem and get prepared to handle impending epidemic of CD.

Background and Aim: While celiac disease is estimated to affect about 1% of the world's population, it is thought to be uncommon not only in India but in Asia also. There is a lack of studies on the prevalence of celiac disease from Asian nations. The aim of the present study was to estimate the prevalence of celiac disease in the community., Methods: In a cross sectional study, we estimated the prevalence of celiac disease in urban and rural populations in the National Capital Region, Delhi, India. A structured questionnaire was administered, by door-to-door visits, to all participants to collect socio-demographic data and to screen for features of celiac disease, namely chronic or recurrent diarrhea and, anemia. In children, additional features, namely short stature (linear height below 5th percentile for age) and failure to thrive/gain weight were also used. All respondents who were screen positive (any one of above) and 10% of screen negative individuals were called for serological testing, which is anti-tissue transglutaminase antibody. All serologically positive respondents were invited to undergo further evaluation including endoscopic biopsy. Celiac disease was diagnosed on the basis of a positive serology, the presence of villous atrophy and/or response to gluten free diet., Result: Among 12,573 contacted, 10,488 (83.4%) (50.6% male) agreed to participate. Based on screening, 5622 (53.6%) participants were screen positive. Of all those screen positive, 2167 (38.5%) agreed for serological testing; additionally 712 (14%) negatives were also tested. The overall sero-prevalence of celiac disease was 1.44% (95% confidence interval [CI] 1.22 1.69) and the overall prevalence of celiac disease was 1.04% (95% CI 0.85 1.25)., Conclusion: The prevalence of celiac disease in this north Indian community is 1 in 96. Celiac disease is more common than is recognized in India., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)