Publications by authors named "Govind K Makharia"

152 Publications

Gut microbiota-derived metabolites in CRC progression and causation.

J Cancer Res Clin Oncol 2021 Jul 17. Epub 2021 Jul 17.

Gene Regulation Laboratory, National Institute of Immunology, New Delhi, 110067, India.

Background: Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host-microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities.

Purpose: In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development.

Conclusion: Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.
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http://dx.doi.org/10.1007/s00432-021-03729-wDOI Listing
July 2021

The Prevalence of the Celiac Disease in Patients with Dyspepsia: A Systematic Review and Meta-Analysis.

Dig Dis Sci 2021 Jul 15. Epub 2021 Jul 15.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

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 = 87.7%). The pooled biopsy-confirmed CeD prevalence was 1.5% (95% CI [1.0, 1.9%]; I = 59.8%) in these patients. Both seroprevalence (Odds ratio: 1.8; 95% CI [0.8, 4.0%]; I = 0%) and prevalence of biopsy-confirmed CeD (Odds ratio: 1.4; 95% CI [0.8, 2.4]; I = 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.
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http://dx.doi.org/10.1007/s10620-021-07142-8DOI Listing
July 2021

Dental enamel defects and oral cavity manifestations in Asian patients with celiac disease.

Indian J Gastroenterol 2021 Jul 10. Epub 2021 Jul 10.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.

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.
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http://dx.doi.org/10.1007/s12664-021-01175-7DOI Listing
July 2021

Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology.

Indian J Pathol Microbiol 2021 Jun;64(Supplement):S8-S31

Department of Pathology, MLN Medical College, Allahabad, Uttar Pradesh, India.

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.
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http://dx.doi.org/10.4103/IJPM.IJPM_1405_20DOI Listing
June 2021

Emergence of Celiac disease and Gluten-related disorders in Asia.

J Neurogastroenterol Motil 2021 Jul;27(3):337-346

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Celiac disease (CeD) is a systemic, immune-mediated enteropathy, which is triggered by gluten protein in genetically susceptible individuals. CeD, once thought to be an uncommon disease, is now recognized to affect approximately 40-60 million people globally. While CeD is now well reported from a few Asian countries such as India, China, Pakistan, and Middle Eastern countries; it is still believed to be uncommon in the rest of Asia. Gluten-related diseases other than CeD, like non-celiac gluten sensitivity (NCGS) are also emerging globally. CeD and NCGS may present with either intestinal or extra-intestinal symptoms, and a proportion of them have overlapping symptoms with irritable bowel syndrome. Hence, many of them are misdiagnosed as having irritable bowel syndrome in clinical practice. In this review, we discuss the emergence of CeD and other gluten-related disorders, both globally and in Asia, the overlapping manifestations between gluten-related disorders and irritable bowel syndrome, and the challenges associated with diagnosis and management of CeD in Asia.
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http://dx.doi.org/10.5056/jnm20140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266496PMC
July 2021

Liver involvement in patients with coeliac disease: proof of causality using IgA/anti-TG2 colocalisation techniques.

J Clin Pathol 2021 Mar 31. Epub 2021 Mar 31.

Gastroenetrology & Human Nutritions, All India Institute of Medical Sciences, New Delhi, Delhi, India.

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.
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http://dx.doi.org/10.1136/jclinpath-2020-206735DOI Listing
March 2021

Prevalence of celiac disease in low and high risk population in Asia-Pacific region: a systematic review and meta-analysis.

Sci Rep 2021 01 27;11(1):2383. Epub 2021 Jan 27.

Gastroenterology and Liver Disease Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran.

This systematic review and meta-analysis study was conducted to estimate the pooled prevalence of CD in low and high risk groups in this region. Following keywords were searched in the Medline, PubMed, Scopus, Web of Science and Cochrane database according to the MeSH terms; celiac disease, prevalence, high risk population and Asian-Pacific region. Prevalence studies published from January 1991 to March 2018 were selected. Prevalence of CD with 95% confidence interval (CI) was calculated using STATA software, version 14. The pooled sero-prevalence of CD among low risk group in Asia-Pacific region was 1.2% (95% CI 0.8-1.7%) in 96,099 individuals based on positive anti-tissue transglutaminase (anti-t-TG Ab) and/or anti-endomysial antibodies (EMA). The pooled prevalence of biopsy proven CD in Asia-Pacific among high and low risk groups was 4.3% (95% CI 3.3-5.5%) and 0.61% (95% CI 0.4-0.8%) in 10,719 and 70,344 subjects, respectively. In addition, the pooled sero-prevalence and prevalence of CD in general population was significantly higher in children compared with adults and it was significantly greater in female vs. male (P < 0.05). Our results suggest high risk individuals of CD are key group that should be specifically targeted for prevention and control measures, and screening may prove to have an optimal cost-benefit ratio.
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http://dx.doi.org/10.1038/s41598-021-82023-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841177PMC
January 2021

Omics technologies for improved diagnosis and treatment of colorectal cancer: Technical advancement and major perspectives.

Biomed Pharmacother 2020 Nov 19;131:110648. Epub 2020 Oct 19.

Gene Regulation Laboratory, National Institute of Immunology, New Delhi 110067, India. Electronic address:

Colorectal cancer (CRC) ranks third among the most commonly occurring cancers worldwide, and it causes half a million deaths annually. Alongside mechanistic study for CRC detection and treatment by conventional techniques, new technologies have been developed to study CRC. These technologies include genomics, transcriptomics, proteomics, and metabolomics which elucidate DNA markers, RNA transcripts, protein and, metabolites produced inside the colon and rectum part of the gut. All these approaches form the omics arena, which presents a remarkable opportunity for the discovery of novel prognostic, diagnostic and therapeutic biomarkers and also delineate the underlying mechanism of CRC causation, which may further help in devising treatment strategies. This review also mentions the latest developments in metagenomics and culturomics as emerging evidence suggests that metagenomics of gut microbiota has profound implications in the causation, prognosis, and treatment of CRC. A majority of bacteria cannot be studied as they remain unculturable, so culturomics has also been strengthened to develop culture conditions suitable for the growth of unculturable bacteria and identify unknown bacteria. The overall purpose of this review is to succinctly evaluate the application of omics technologies in colorectal cancer research for improving the diagnosis and treatment strategies.
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http://dx.doi.org/10.1016/j.biopha.2020.110648DOI Listing
November 2020

Opportunities and challenges in the management of celiac disease in Asia.

JGH Open 2020 Oct 11;4(5):795-799. Epub 2020 Jul 11.

Department of Gastroenterology and Human Nutrition All India Institute of Medical Sciences New Delhi India.

Although once considered uncommon, there is increasing recognition of celiac disease (CeD) in Asia. It is now clear that CeD is a disorder as frequent in certain Asian countries as that in western countries, although it often remains undiagnosed. With increasing awareness and diagnosis, the absolute numbers of celiac patients are expected to increase markedly in Asia. Asia, with 60% of the population of the world, is probably the major "reservoir" of undiagnosed CeD in the world. As Asia has a huge landscape along with highly heterogenous genetic, social, cultural, and nutritional practices, similar heterogeneity is seen in the epidemiology, diagnostic, and therapeutic facilities for CeD in Asia. In this article, we have reviewed the changes in the epidemiology, diagnostics, and management of CeD in Asia and summarized the challenges and opportunities for its emergence in Asia.
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http://dx.doi.org/10.1002/jgh3.12381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578313PMC
October 2020

Prevalence of elevated alanine aminotransferase levels in adult participants from a community-based study from northern part of India.

Indian J Gastroenterol 2020 Dec 24;39(6):608-613. Epub 2020 Oct 24.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.

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.
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http://dx.doi.org/10.1007/s12664-020-01091-2DOI Listing
December 2020

Comparison of Contrast-Enhanced CT + CT Enterography and 68Ga-DOTANOC PET/CT in Gastroenteropancreatic Neuroendocrine Tumors.

Clin Nucl Med 2020 Nov;45(11):848-853

From the Departments of Nuclear Medicine.

Background: Increase in incidence of neuroendocrine tumors (NETs) has been attributed in part to the availability of sensitive diagnostic modalities, such as Ga-DOTA-peptide PET/CT. However, it suffers from problems such as obscurement of tracer-avid lesions by physiological gut activity and collapsed gut lumen. Contrast-enhanced CT and CT enterography (CTE) do not have these drawbacks.

Purpose: The aim of this study was to compare the diagnostic performances of contrast-enhanced CT + CTE and the Ga-DOTA-peptide PET/noncontrast CT in GEP-NETs.

Methods: Fifty-six patients (mean age, 57.8 ± 13.3 years [male:female, 1.95:1]), with histopathologically proven gastroenteropancreatic NETs, who had undergone both Ga-DOTANOC-PET/NCCT (60 minutes, post-IV injection of 111-185 MBq) and contrast-enhanced CT (CECT) + CTE (using 1.5-2 L isotonic mannitol solution and 1-2 mg/kg of IV contrast), were retrospectively selected. Twenty-three patients had been referred for identification of primary lesions and 33 for staging/restaging. The scans were independently evaluated by 2 blinded physicians, who documented the number and site of lesions, with reporting confidence (3 = high confidence, 2 = equivocal confidence, 1 = low confidence). Reference standard was created using clinical, biochemical, and imaging parameters (ie, uptake and contrast enhancement), along with corroboration from previous or follow-up scans. Finally, PET images coregistered to the CECT + CTE were independently evaluated for any additional benefit.

Results: The numbers of primary lesions detected by CECT + CTE and PET/CT were 69 and 57, respectively. Lesion-wise sensitivities for patients with unknown primary in CECT + CTE and PET/CT were 57.7% (95% confidence interval [CI], 39.0%-74.5%) and 71.4% (95% CI, 52.9%-84.7%), respectively. Corresponding numbers in patients who had come for staging/restaging were 73.2% (95% CI, 58.1%-84.3%) and 73.8% (95% CI, 58.9%-84.7%). Lesions missed in CECT + CTE were gastrointestinal (n = 14), lymph nodes (n = 25), mesenteric (n = 1), and pancreatic (n = 7), whereas corresponding numbers for PET/CT were 14, 5, 3, and 2. Contrast-enhanced CT + CTE showed more false-positives (n = 26) than PET/CT (n = 9). Lesions missed by CECT + CTE were smaller than detected lesions (median, 9.7 mm [interquartile range, 7.5-31.1] vs 17.7 mm [interquartile range, 12.2-30.0]; P = 0.062), and lesions missed by PET had significantly lower tumor/background (liver) SUVmax ratio (median, 1.3 [interquartile range, 0.6-3.8] vs 4.7 [interquartile range, 2.7-10.8]). The ratio of true-positives to false-positives dropped markedly, when reporting confidence in CECT + CTE was low (4/15 [for rating 1 or 2] vs 93/11 [rating 3]). Corresponding numbers for PET/CT were (40/7 [for rating 1 or 2] vs 80/2 [rating 3]). Combination of these 2 modalities would have increased the lesion-wise sensitivities in patients with unknown primaries to 89.7% (95% CI, 73.6%-96.4%) and the confidence rating of soft tissue lesions to predominantly high (134 lesions rated 3, and 10 rated 1 or 2).

Conclusions: PET/CT is a sensitive modality for staging and restaging well-differentiated NETs. Use of CECT + CTE as a complementary modality in patients with uncertain uptake or high clinical suspicion of gastroenteropancreatic NETs should be considered, as it improves the lesion detection and reporting confidence.
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http://dx.doi.org/10.1097/RLU.0000000000003188DOI Listing
November 2020

Prevalence of celiac disease in patients with short stature: A systematic review and meta-analysis.

J Gastroenterol Hepatol 2021 Jan 23;36(1):44-54. Epub 2020 Aug 23.

Department of Gastroenterology and Human nutrition, All India Institute of Medical Sciences, Delhi, New Delhi, India.

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  = 86%) and 9.7% (95% CI 2.7-20.2%; I  = 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  = 76%) and 11.6% (95% CI 4.1-22.2%; I  = 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.
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http://dx.doi.org/10.1111/jgh.15167DOI Listing
January 2021

Asian Pacific Association of Gastroenterology (APAGE) Inflammatory Bowel Disease (IBD) Working Party guidelines on IBD management during the COVID-19 pandemic.

JGH Open 2020 Jun 5;4(3):320-323. Epub 2020 Jun 5.

Duke-NUS Medical School Singapore.

The COVID-19 pandemic, secondary to SARS-CoV-2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long-term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face-to-face clinic follow ups and non-urgent procedures should be kept to a minimum.
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http://dx.doi.org/10.1002/jgh3.12362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273734PMC
June 2020

Abnormalities in metabolic pathways in celiac disease investigated by the metabolic profiling of small intestinal mucosa, blood plasma and urine by NMR spectroscopy.

NMR Biomed 2020 08 11;33(8):e4305. Epub 2020 May 11.

Department of NMR and MRI Facility, All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.1002/nbm.4305DOI Listing
August 2020

Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver.

Intest Res 2021 Jan 22;19(1):106-114. Epub 2020 Apr 22.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Background/aims: Gluten-free diet has an excess of fats and simple sugars and puts patients with celiac disease at risk of metabolic complications including metabolic syndrome and fatty liver. We assessed prevalence of metabolic syndrome and fatty liver in two cohorts of celiac disease.

Methods: Study was done in 2 groups. In group 1, 54 treatment naïve patients with celiac disease were recruited. Of them, 44 returned after 1-year of gluten-free diet and were reassessed. In group 2, 130 celiac disease patients on gluten-free diet for ≥1 year were recruited. All patients were assessed for anthropometric and metabolic parameters and fatty liver. Metabolic syndrome was defined as per consensus definition for Asian Indians. Fatty liver was defined as controlled attenuation parameter value >263 decibels by FibroScan.

Results: In group 1, of 44 treatment naïve patients with celiac disease, metabolic syndrome was present in 5 patients (11.4%) at baseline and 9 (18.2%) after 1 year of gluten-free diet. Patients having fatty liver increased from 6 patients (14.3%) at baseline to 13 (29.5%) after 1year of gluten-free diet (P=0.002). In group 2, of 130 patients with celiac disease on gluten-free diet for a median duration of 4 years, 30 out of 114 (26.3%) and 30 out of 130 patients (23%) had metabolic syndrome and fatty liver, respectively.

Conclusions: Patients with celiac disease are at high risk of developing metabolic syndrome and fatty liver, which increases further with gluten-free diet. These patients should be assessed for nutritional and metabolic features and counseled about balanced diet and physical activity regularly.
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http://dx.doi.org/10.5217/ir.2019.00136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873403PMC
January 2021

The spectrum of clinical and subclinical endocrinopathies in treatment-naïve patients with celiac disease.

Indian J Gastroenterol 2019 12 26;38(6):518-526. Epub 2019 Dec 26.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India.

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.
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http://dx.doi.org/10.1007/s12664-019-01006-wDOI Listing
December 2019

Indian consensus on gastroesophageal reflux disease in adults: A position statement of the Indian Society of Gastroenterology.

Indian J Gastroenterol 2019 10 5;38(5):411-440. Epub 2019 Dec 5.

Apollo Hospitals, Bilaspur, 495 006, India.

The Indian Society of Gastroenterology developed this evidence-based practice guideline for management of gastroesophageal reflux disease (GERD) in adults. A modified Delphi process was used to develop this consensus containing 58 statements, which were generated by electronic voting iteration as well as face-to-face meeting and review of the supporting literature primarily from India. These statements include 10 on epidemiology, 8 on clinical presentation, 10 on investigations, 23 on treatment (including medical, endoscopic, and surgical modalities), and 7 on complications of GERD. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The prevalence of GERD in India ranges from 7.6% to 30%, being  < 10% in most population studies, and higher in cohort studies. The dietary factors associated with GERD include use of spices and non-vegetarian food. Helicobacter pylori is thought to have a negative relation with GERD; H. pylori negative patients have higher grade of symptoms of GERD and esophagitis. Less than 10% of GERD patients in India have erosive esophagitis. In patients with occasional or mild symptoms, antacids and histamine H receptor blockers (H2RAs) may be used, and proton pump inhibitors (PPI) should be used in patients with frequent or severe symptoms. Prokinetics have limited proven role in management of GERD.
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http://dx.doi.org/10.1007/s12664-019-00979-yDOI Listing
October 2019

All that a physician should know about FODMAPs.

Indian J Gastroenterol 2019 10 4;38(5):378-390. Epub 2019 Dec 4.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India.

A diet low in poorly absorbed, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is now considered as an effective strategy for symptoms control in patients with irritable bowel syndrome (IBS). The low FODMAP diet is administered in three phases, namely restriction of all dietary FODMAPs followed by rechallenge and then reintroduction of specific FODMAPs according to the tolerance of patients. A dietician should be involved in patients in whom a low FODMAP diet is planned. While restricting high FODMAPs, it is pertinent that patients are advised a well-balanced diet and suitable alternatives with low FODMAP contents in each food groups are prescribed. Strict adherence to a low FODMAP diet has been shown to improve symptoms, stool output, quality of life, and the overall well-being of patients with IBS. For those who do not respond to this dietary approach, a normal diet may be initiated and other treatment strategies (dietary or nondietary) should be considered. Interestingly, the low FODMAP diet has also been tried in other functional disorders, nonceliac gluten sensitivity, and even inflammatory bowel disease. Since the concept of FODMAP is relatively new, there is only limited data on the content of FODMAP in the Indian food items and there is a need to address this question. There is also a need for well-designed and adequately powered studies to explore the efficacy of low FODMAP diet in patients with IBS. In the present review article, we have compiled all the relevant information about FODMAPs with an objective to provide comprehensive information on FODMAPs to a physician.
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http://dx.doi.org/10.1007/s12664-019-01002-0DOI Listing
October 2019

Prevalence of thyroid autoimmunity in first-degree relatives of patients with celiac disease.

Indian J Gastroenterol 2019 10 8;38(5):450-455. Epub 2019 Nov 8.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India.

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.
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http://dx.doi.org/10.1007/s12664-019-00990-3DOI Listing
October 2019

Inter- and Intra-assay Variation in the Diagnostic Performance of Assays for Anti-tissue Transglutaminase in 2 Populations.

Clin Gastroenterol Hepatol 2020 10 20;18(11):2628-2630. Epub 2019 Sep 20.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Tissue transglutaminse-2 (TG2)-based immunoassays are the cornerstone of diagnosis in celiac disease (CeD), with a reported pooled sensitivity as high as 98%. However, a few small, single-center studies have questioned their sensitivity in clinical practice. Moreover, commercial kits use variable TG2 antigens, 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.
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http://dx.doi.org/10.1016/j.cgh.2019.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082178PMC
October 2020

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease.

J Gastroenterol Hepatol 2020 Mar 30;35(3):438-445. Epub 2019 Oct 30.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

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.
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http://dx.doi.org/10.1111/jgh.14852DOI Listing
March 2020

Duodenal mucosal immune cells in treatment-naive adult patients with celiac disease having different histological grades and controls.

Indian J Pathol Microbiol 2019 Jul-Sep;62(3):399-404

Department of Gastroenterology and Human Nutritions, AIIMS, New Delhi, India.

Background: It is hypothesized that the duodenal mucosal damage in patients with celiac disease (CeD) is caused by the mucosa-infiltrating lymphoid cells. This study aimed to analyze the immune effective and regulatory T (Treg) cells in duodenal biopsies from treatment-naive adult patients with CeD having different histological grades and controls.

Patients And Methods: Dual-color immunohistochemical staining was done in a total of 234 duodenal biopsies, including 132 controls and 102 adult patients with CeD using CD20, CD3:CD4, CD3:CD8, CD4:FoxP3, CD8:FoxP3, and TCRαβ:TCRγδ antibodies. The density of these lymphoid cells in lamina propria and mucosal epithelium was compared between controls and CeD, with different modified Marsh grades.

Results: Densities of CD4+ T cells in lamina propria and CD8+γδ intraepithelial lymphocytes (IELs) were significantly more in biopsies from patients with CeD, than in controls. An increasing linear pattern of IELs, CD3+ T cells, and CD20+ B cells was observed with increasing grades of villous abnormalities. Although CD8+ FoxP3+ Treg cells were significantly more in biopsies from patients with CeD, there was no significant difference in CD4+ FoxP3+ Treg cell infiltrate between both the groups.

Conclusion: Our finding in this observational study generates interest to study the local intestinal mucosal immunity in CeD in detail. A study to prove the failure of CD4+ FoxP3+ Treg cell recruitment in CeD and its direct functional impact may yield valuable information regarding loss of mucosal tolerance.
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http://dx.doi.org/10.4103/IJPM.IJPM_703_18DOI Listing
December 2019

Celiac disease in the East and the West: Bridging the gaps between the guidelines and their implementation in daily practice is mandatory.

Indian J Gastroenterol 2019 06;38(3):185-189

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110 029, India.

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http://dx.doi.org/10.1007/s12664-019-00970-7DOI Listing
June 2019

Non-Invasive Biomarkers for Celiac Disease.

J Clin Med 2019 Jun 21;8(6). Epub 2019 Jun 21.

Department of Gastroenterology and Human Nutrition; All India Institute of Medical Sciences, New Delhi-110029, India.

Once thought to be uncommon, celiac disease has now become a common disease globally. While avoidance of the gluten-containing diet is the only effective treatment so far, many new targets are being explored for the development of new drugs for its treatment. The endpoints of therapy include not only reversal of symptoms, normalization of immunological abnormalities and healing of mucosa, but also maintenance of remission of the disease by strict adherence of the gluten-free diet (GFD). There is no single gold standard test for the diagnosis of celiac disease and the diagnosis is based on the presence of a combination of characteristics including the presence of a celiac-specific antibody (anti-tissue transglutaminase antibody, anti-endomysial antibody or anti-deamidated gliadin peptide antibody) and demonstration of villous abnormalities. While the demonstration of enteropathy is an important criterion for a definite diagnosis of celiac disease, it requires endoscopic examination which is perceived as an invasive procedure. The capability of prediction of enteropathy by the presence of the high titer of anti-tissue transglutaminase antibody led to an option of making a diagnosis even without obtaining mucosal biopsies. While present day diagnostic tests are great, they, however, have certain limitations. Therefore, there is a need for biomarkers for screening of patients, prediction of enteropathy, and monitoring of patients for adherence of the gluten-free diet. Efforts are now being made to explore various biomarkers which reflect different changes that occur in the intestinal mucosa using modern day tools including transcriptomics, proteomics, and metabolomics. In the present review, we have discussed comprehensively the pros and cons of available biomarkers and also summarized the current status of emerging biomarkers for the screening, diagnosis, and monitoring of celiac disease.
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http://dx.doi.org/10.3390/jcm8060885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6616864PMC
June 2019

Evolving Therapy for Celiac Disease.

Front Pediatr 2019 14;7:193. Epub 2019 May 14.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Gluten is known to be the main triggering factor for celiac disease (CeD), an immune-mediated disorder. CeD is therefore managed using a strict and lifelong gluten-free diet (GFD), the only effective treatment available currently. However, the GFD is restrictive. Hence, efforts are being made to explore alternative therapies. Based on their mechanisms of action on various molecular targets involved in the pathogenesis of CeD, these therapies may be classified into one of the following five broad approaches. The first approach focuses on decreasing the immunogenic content of gluten, using strategies like genetically modified wheat, intra-intestinal gluten digestion using glutenases, microwave thermal treatment of hydrated wheat kernels, and gluten pretreatment with either bacterial/ fungal derived endopeptidases or microbial transglutaminase. The second approach involves sequestering gluten in the gut lumen before it is digested into immunogenic peptides and absorbed, using binder drugs like polymer p(HEMA-co-SS), single chain fragment variable (scFv), and anti- gluten antibody AGY. The third approach aims to prevent uptake of digested gluten through intestinal epithelial tight junctions, using a zonulin antagonist. The fourth approach involves tissue transglutaminase (tTG) inhibitors to prevent the enhancement of immunogenicity of digested gluten by the intestinal tTG enzyme. The fifth approach seeks to prevent downstream immune activation after uptake of gluten immunogenic peptides through the intestinal mucosal epithelial layer. Examples include HLA-DQ2 blockers that prevent presentation of gluten derived- antigens by dendritic cells to T cells, immune- tolerizing therapies like the vaccine Nexvax2 and TIMP-Glia, cathepsin inhibitors, immunosuppressants like corticosteroids, azathioprine etc., and anti-cytokine agents targeting TNF-α and interleukin-15. Apart from these approaches, research is being done to evaluate the effectiveness of probiotics/prebiotics, helminth therapy using , low FODMAP diet, and pancreatic enzyme supplementation in CeD symptom control; however, the mechanisms by which they play a beneficial role in CeD are yet to be clearly established. Overall, although many therapies being explored are still in the pre-clinical phase, some like the zonulin antagonist, immune tolerizing therapies and glutenases have reached phase II/III clinical trials. While these potential options appear exciting, currently they may at best be used to supplement rather than supplant the GFD.
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http://dx.doi.org/10.3389/fped.2019.00193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530343PMC
May 2019

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

Intest Res 2019 Jul 31;17(3):285-310. Epub 2019 May 31.

Department of Medicine, Chulalongkorn University, Bangkok, Thailand.

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn's disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
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http://dx.doi.org/10.5217/ir.2019.00026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667368PMC
July 2019

Quantitative histology-based classification system for assessment of the intestinal mucosal histological changes in patients with celiac disease.

Intest Res 2019 Jul 22;17(3):387-397. Epub 2019 Apr 22.

Departments of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Background/aims: The existing histological classifications for the interpretation of small intestinal biopsies are based on qualitative parameters with high intraobserver and interobserver variations. We have developed and propose a quantitative histological classification system for the assessment of intestinal mucosal biopsies.

Methods: We performed a computer-assisted quantitative histological assessment of digital images of duodenal biopsies from 137 controls and 124 patients with celiac disease (CeD) (derivation cohort). From the receiver-operating curve analysis, followed by multivariate and logistic regression analyses, we identified parameters for differentiating control biopsies from those of the patients with CeD. We repeated the quantitative histological analysis in a validation cohort (105 controls and 120 patients with CeD). On the basis of the results, we propose a quantitative histological classification system. The new classification was compared with the existing histological classifications for interobserver and intraobserver agreements by a group of qualified pathologists.

Results: Among the histological parameters, intraepithelial lymphocyte count of ≥25/100 epithelial cells, adjusted villous height fold change of ≤0.7, and crypt depth-to-villous height ratio of ≥0.5 showed good discriminative power between the mucosal biopsies from the patients with CeD and those from the controls, with 90.3% sensitivity, 93.5% specificity, and 96.2% area under the curve. Among the existing histological classifications, our quantitative histological classification showed the highest intraobserver (69.7%-85.03%) and interobserver (24.6%-71.5%) agreements.

Conclusions: Quantitative assessment increases the reliability of the histological assessment of mucosal biopsies in patients with CeD. Such a classification system may be used for clinical trials in patients with CeD. (Intest Res, Published online).
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http://dx.doi.org/10.5217/ir.2018.00167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667359PMC
July 2019

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

J Gastroenterol Hepatol 2019 Aug 1;34(8):1296-1315. Epub 2019 Jul 1.

Department of Medicine, Chulalongkorn University, Bangkok, Thailand.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.
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http://dx.doi.org/10.1111/jgh.14648DOI Listing
August 2019

Comparison of Small Gut and Whole Gut Microbiota of First-Degree Relatives With Adult Celiac Disease Patients and Controls.

Front Microbiol 2019 8;10:164. Epub 2019 Feb 8.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.

Recent studies on celiac disease (CeD) have reported alterations in the gut microbiome. Whether this alteration in the microbial community is the cause or effect of the disease is not well understood, especially in adult onset of disease. The first-degree relatives (FDRs) of CeD patients may provide an opportunity to study gut microbiome in pre-disease state as FDRs are genetically susceptible to CeD. By using 16S rRNA gene sequencing, we observed that ecosystem level diversity measures were not significantly different between the disease condition (CeD), pre-disease (FDR) and control subjects. However, differences were observed at the level of amplicon sequence variant (ASV), suggesting alterations in specific ASVs between pre-disease and diseased condition. Duodenal biopsies showed higher differences in ASVs compared to fecal samples indicating larger disruption of the microbiota at the disease site. The duodenal microbiota of FDR was characterized by significant abundance of ASVs belonging to , and genera. The duodenal microbiota of CeD was characterized by higher abundance of ASVs from genera and compared to the FDR microbiota. The CeD and FDR fecal microbiota had reduced abundance of ASVs classified as and when compared to control group microbiota. In addition, predicted functional metagenome showed reduced ability of gluten degradation by CeD fecal microbiota in comparison to FDRs and controls. The findings of the present study demonstrate differences in ASVs and predicts reduced ability of CeD fecal microbiota to degrade gluten compared to the FDR fecal microbiota. Further research is required to investigate the strain level and active functional profiles of FDR and CeD microbiota to better understand the role of gut microbiome in pathophysiology of CeD.
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http://dx.doi.org/10.3389/fmicb.2019.00164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376745PMC
February 2019

Celiac Disease in Asia.

Gastroenterol Clin North Am 2019 03 13;48(1):101-113. Epub 2018 Dec 13.

Department of Pediatrics, Center for Celiac Research, Università Politecnica delle Marche, Piazzale Martelli Raffaele, 8, Ancona, Ancona 60121, Italy; Division of Pediatric Gastroenterology, Massachussets General Hospital, Boston, MA 33131, USA.

Celiac disease, once thought to be very uncommon in Asia, is now emerging in many Asian countries. Although the absolute number of patients with celiac disease at present is not very high, this number is expected to increase markedly over the next few years/decades owing to increasing awareness. It is now that the medical community across the Asia should define the extent of the problem and prepare to handle the impending epidemic of celiac disease in Asia.
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http://dx.doi.org/10.1016/j.gtc.2018.09.007DOI Listing
March 2019
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