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Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE–APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

The Asia-Pacific region has the largest number of cases of colorectal cancer (CRC) and one of the highest levels of mortality due to this condition in the world. Since the publishing of two consensus recommendations in 2008 and 2015, significant advancements have been made in our knowledge of epidemiology, pathology and the natural history of the adenoma-carcinoma progression. Based on the most updated epidemiological and clinical studies in this region, considering literature from international studies, and adopting the modified Delphi process, the Asia-Pacific Working Group on Colorectal Cancer Screening has updated and revised their recommendations on (1) screening methods and preferred strategies; (2) age for starting and terminating screening for CRC; (3) screening for individuals with a family history of CRC or advanced adenoma; (4) surveillance for those with adenomas; (5) screening and surveillance for sessile serrated lesions and (6) quality assurance of screening programmes. Thirteen countries/regions in the Asia-Pacific region were represented in this exercise. International advisors from North America and Europe were invited to participate.

The patients with positive celiac disease (CeD) specific serology, but no evidence of intestinal inflammation are defined as potential celiac disease (PCeD) patients. About one-third of PCeD patients develop intestinal inflammation over time. The present study investigated the metabolome of small intestinal biopsies, blood plasma, and urine of patients with PCeD to understand the biochemical changes underlying the CeD.The metabolic profiles of small intestinal biopsies, blood plasma, and urine of patients with PCeD (n = 7) were compared with CeD (n = 64) and controls (n = 15) [disease controls (DC) and healthy controls (HC)] usingThe intestinal mucosa of PCeD showed lower levels of histidine, glycine, tyrosine, and tryptophan compared to DC. Altered levels of 6 metabolites (glucose, acetate, acetoacetate, β-hydroxybutyrate, pyruvate, arginine) in blood plasma and two metabolites (succinate and aminohippurate) in urine were observed in PCeD compared to HC. The PLS-DA model built on the concentration of blood plasma showed separate clustering for PCeD and CeD patients.Altered metabolic profile of PCeD suggested that gluten intolerance was evident at the metabolic level before the intestinal damage. Altered energy metabolism and lower cytoprotective activity (histidine, glycine, arginine) indicated vulnerability to develop intestinal inflammation in PCeD over time. Our study may provide an insight into early biochemical processes of the progression of PCeD to CeD.

Background/Aims: Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB. Methods: Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs. Results: Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.Conclusions: Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of “completely accepted” and “accepted with minor reservation” voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Symptomatic evaluation using Eckardt score and achalasia-specific health-related quality-of-life and physiological evaluation using timed barium examination (TBE) and high-resolution manometry is integral to the diagnosis of achalasia. However, the correlation of physiological outcomes with symptomatic outcomes and their role in routine follow-up after laparoscopic Heller cardiomyotomy (LHCM) is controversial. In this study, we evaluated the role of physiological testing in achalasia patients undergoing LHCM and its correlation with symptomatic evaluation.Case records of patients undergoing LHCM for achalasia between January 2017 and March 2020 were reviewed for symptom scores (Eckardt score and achalasia-specific health-related quality-of-life) and physiological parameters [5-min column height on TBE and median integrated relaxation pressure (IRP) on high-resolution manometry]. Sixty-one patients with complete data in the preoperative period and on follow-up were included in the study. The data was analyzed for symptomatic and physiological outcomes and their correlation using paired t test and the Spearman correlation test.At a median follow-up of 16 months following LHCM, there was a significant improvement in Eckardt score (7.03±1.53 to 0.93±1.10, P0.001), achalasia-specific health-related quality-of-life (58.34±7.81 to 14.57±13.45, P0.001), column height on TBE (115.14±46.9 to 27.89±34.31, P0.001) and IRP (23.95±8.26 to 4.61±4.11, P0.001). Eckardt score correlated significantly with achalasia-specific health-related quality-of-life scores preoperatively (ρ=0.410, P0.001) and on follow-up (ρ=0.559, P0.001). There was no correlation between symptomatic parameters and physiological parameters.In patients of achalasia, LHCM leads to significant improvement in symptomatic and physiological parameters. Symptom scores correlate among themselves but not with physiological scores. Thus, physiological testing may not be needed for routine follow-up.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.

Aims Lockdown and restricted mobility due to the pandemic of corona virus disease 2019 (COVID-19) has severely affected the continuity of healthcare of patients with acute and chronic diseases. We evaluated the impact of COVID-19 on the adherence to gluten-free diet (GFD), symptom control, and quality of life (QOL) in patients with celiac disease (CeD). Methods A questionnaire, consisting of both ad-hoc and validated questions, was created after review of literature, group discussions, and expert meetings. Standardized questionnaires namely CeD adherence test (CDAT), celiac symptom index score, and CeD-related QOL were used. The web-based questionnaire was sent to 3130 patients via social media and 452 responses (14.4%) were received. Also, additional 68 patients (not available on any social media application) were interviewed telephonically by a trained dietitian. Results Overall, 505 patients (females: 318; mean age: 24.1±14.2 years) were included. While only 6.7% (n = 34) had poor compliance to GFD (CDAT > 17) before COVID-19 pandemic, it almost doubled to 12.6% (n = 64) during the COVID-19 pandemic times (p = 0.02). Furthermore, 4.9% (n = 25) of patients were diagnosed contacting COVID-19. Interestingly, 73.2% (n = 370) patients preferred online appointment than physical appointment. Most common difficulties faced during lockdown period were high delivery charges for getting gluten-free (GF) food at home (54.4%), increased prices of regular GF food (43.1%), and travelling long distance to arrange GF food (44.9%). Conclusions The COVID-19 pandemic has substantially affected the adherence, symptom control, and QOL in patients with CeD, attributable to unavailability, shortage of money, and heightened cost of GF food. The pandemic has offered an opportunity to practice teleconsultation approach for patients with CeD. Supplementary Information The online version contains supplementary material available at 10.1007/s12664-021-01213-4.

Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium.

Background/Aims: Predictors of short-term outcome of intravenous (IV) steroid therapy in acute severe ulcerative colitis (ASUC) have been well described, but the impact of cytomegalovirus (CMV) infection as a predictor of outcome remains debatable. We investigated the role of quantitative CMV polymerase chain reaction (PCR) as a predictor of short-term outcome in patients with ASUC.Methods: Consecutive patients with ASUC satisfying Truelove and Witts criteria hospitalized at All India Institute of Medical Sciences (AIIMS) from May 2016 to July 2019 were included; all received IV steroid. The primary outcome measure was steroid-failure defined as the need for rescue therapy (with ciclosporin or infliximab) or colectomy during admission. AIIMS’ index (ulcerative colitis index of severity > 6 at day 1+fecal calprotectin > 1,000 μg/g at day 3), with quantitative CMV PCR on biopsy samples obtained at initial sigmoidoscopy were correlated with the primary outcome.Results: Thirty of 76 patients (39%) failed IV corticosteroids and 12 (16%) underwent surgery. Patients with steroid failure had a significantly higher mucosal CMV DNA than responders (3,454 copies/mg [0–2,700,000] vs. 116 copies/mg [0–27,220]; P< 0.01). On multivariable analysis, mucosal CMV DNA load > 2,000 copies/mg (odds ratio [OR], 10.2; 95% confidence interval [CI], 2.6–39.7; P< 0.01) and AIIMS’ index (OR, 39.8; 95% CI, 4.4–364.4; P< 0.01) were independent predictors of steroid-failure and need for colectomy. The combination correctly predicted outcomes in 84% of patients with ASUC.Conclusions: High mucosal CMV DNA ( > 2,000 copies/mg) independently predicts failure of IV corticosteroids and short-term risk of colectomy and it has an additional value to the established markers of disease severity in patients with ASUC.

Aim: We conducted this network meta-analysis to compare the efficacy and safety of targeted pharmacotherapies and fecal microbial transplantation (FMT). Patients & methods: Nineteen studies were included and there was only one head-to-head randomized controlled trial (adalimumab vs vedolizumab). Results: All interventions, including FMT, were superior to a placebo in inducing clinical remission (except adalimumab – odds ratio 1.66; 95% CI: 0.97–2.85), clinical response and endoscopic remission. FMT was comparable with other agents in achieving all efficacy outcomes. Infliximab was ranked highest in inducing clinical remission (surface under the cumulative ranking, 0.8). There was no difference in safety outcomes between FMT and other targeted therapies. Conclusion: FMT is as efficacious and as safe as other targeted therapies in inducing clinical remission, clinical response and endoscopic remission. Further studies to assess the long-term benefits are needed in order to reach a definitive conclusion.

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. To explore the utility of IgA anti-TG2 Ab deposits in pan-gastrointestinal mucosal biopsies as evidence of CeD-related pathologies. 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. Significantly higher number of patients with CeD had lymphocytic esophagitis (9.7% vs. 0%, P = 0.05), lymphocytic gastritis (35% vs. 8.8%, P

Facebook (FB) is the most popular online networking platform. There are several FB pages dedicated to spreading awareness about the Celiac disease (CD). To get the latest information, a huge number of CD patients follow Celiac disease Facebook (CD-FB) pages. Such pages frequently post beneficial information. However, very less is known if they provide appropriate information to CD patients. We conducted this study to know if CD-FB pages spread misleading information to CD patients. CD-FB pages from three celiac-influenced countries were explored using the FB platform and Google search engine. From October 2021 to April 2022, a total of 147 CD-FB, Italy (n=63), the USA (n=46), and India (n=38), were found eligible. Of them, 13% of pages (followers Mean±SD; Italy 2478±2011; USA 12635±12486; India 667±313) shared misleading information, particularly about gluten-free ingredients, and treatment of CD. In total,16% of CD-FB pages discussed alternative treatments option. Surprisingly, 7% of pages (followers Mean±SD; USA 23800±10465; India 628±333) supported alternative treatments for CD. CD-FB pages are useful for disseminating celiac-related information. While most of such pages provide useful information, a few pages sometimes contain misleading information. CD patients must consult their treating unit before following any uncertain information posted on CD-FB pages.

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.

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. 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. 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%], I2 = 87.7%). The pooled biopsy-confirmed CeD prevalence was 1.5% (95% CI [1.0, 1.9%]; I2 = 59.8%) in these patients. Both seroprevalence (Odds ratio: 1.8; 95% CI [0.8, 4.0%]; I2 = 0%) and prevalence of biopsy-confirmed CeD (Odds ratio: 1.4; 95% CI [0.8, 2.4]; I2 = 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. 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.

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. We recruited 118 patients with biopsy-confirmed CeD (36 treatment naive 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. Overall higher number of patients with CeD (66.9%), both treatment naive (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

The Indian Society of Gastroenterology (ISG) felt the need to organize a consensus on Helicobacter pylori (H. pylori) infection and to update the current management of H. pylori infection; hence, ISG constituted the ISG's Task Force on Helicobacter pylori. The Task Force on H. pylori undertook an exercise to produce consensus statements on H. pylori infection. Twenty-five experts from different parts of India, including gastroenterologists, pathologists, surgeons, epidemiologists, pediatricians, and microbiologists participated in the meeting. The participants were allocated to one of following sections for the meeting: Epidemiology of H. pylori infection in India and H. pylori associated conditions; diagnosis; treatment and retreatment; H. pylori and gastric cancer, and H. pylori prevention/public health. Each group reviewed all published literature on H. pylori infection with special reference to the Indian scenario and prepared appropriate statements on different aspects for voting and consensus development. This consensus, which was produced through a modified Delphi process including two rounds of face-to-face meetings, reflects our current understanding and recommendations for the diagnosis and management of H. pylori infection. These consensus should serve as a reference for not only guiding treatment of H. pylori infection but also to guide future research on the subject.

Background/Aims: Exclusive enteral nutrition (EEN), an established modality for pediatric Crohn’s disease (CD) is seldomly utilized in adults. The present study reports the outcome of EEN in adult CD patients at a tertiary care hospital in India.Methods: This was a retrospective analysis of CD patients who received EEN as a sole modality/adjunct to other treatment. The primary and secondary outcomes changed in Crohn’s Disease Activity Index (CDAI), and clinical response (decline in CDAI > 70), respectively, at 4 and 8 weeks. Subgroup analysis evaluated response across different phenotypes, EEN formulations and prior treatment. Linear mixed effect model was created to assess the predictors of EEN response.Results: Thirty-one CD patients received EEN over median duration of 4 weeks (range, 2–6 weeks). CDAI showed a significant improvement post EEN at 4 (baseline 290 [260–320] vs. 240 [180–280], P= 0.001) and 8 weeks (baseline 290 [260–320] vs. 186 [160–240], P= 0.001), respectively. The cumulative clinical response rates at 4 and 8 weeks were 37.3% and 80.4% respectively. The clinical response rates at 8 weeks across B1 (n = 4), B2 (n = 18) and B3 (n = 9) phenotypes were 50%, 78.8% and 100% respectively (log-rank test, P= 0.093). The response rates at 8 weeks with polymeric (n = 8) and semi-elemental diet (n = 23) were 75% and 82.6%% respectively (log-rank test, P= 0.49). Baseline CDAI (odds ratio, 1.008; 95% confidence interval, 1.002–1.017; P= 0.046) predicted response to EEN.Conclusions: EEN was effective in inducing clinical response across different phenotypes of CD. Baseline disease activity remained the most important predictor of clinical response to EEN.

Background/Aims: Crohn’s disease (CD) and intestinal tuberculosis (ITB) remain “difficult-to-differentiate” diseases. We have previously documented peripheral blood frequency of CD4+CD25+FOXP3+ T-regulatory cells (Treg) as a biomarker to differentiate CD and ITB. We tried to validate these results in a larger cohort of CD and ITB patients. Methods: Seventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 to May 2017. Patients with history of antitubercular therapy in the past were excluded. The frequency of Treg cells in peripheral blood was determined by flow cytometry, and compared between CD and ITB patients. Results: Similar to our previous study, frequency of Treg cells in peripheral blood was significantly increased in ITB as compared to CD patients (40.9 [interquartile range, 33–50] vs. 24.9 [interquartile range, 14.4–29.6], P< 0.001). Further, the receiver operating characteristics curve also showed good diagnostic accuracy with an area under the curve (AUC) of 0.77 (95% confidence interval, 0.65–0.89) and a FOXP3+ cutoff value of > 31.3% had a sensitivity and specificity of 83% and 82.6% respectively, to differentiate ITB from CD. Even for the indeterminate cases (n = 33), Treg cell frequency had similar diagnostic accuracy with an AUC of 0.85 (95% confidence interval, 0.68–0.95) and a cutoff of 32.37% had sensitivity and specificity of 87% and 95% respectively, to differentiate ITB from CD. Conclusions: The current findings validate that the increased frequency of CD4+CD25+FOXP3+ Treg in the peripheral blood can be used as a biomarker with high diagnostic accuracy to differentiate ITB from CD.

AimsDespite clinical evidence of liver involvement in patients with coeliac disease (CeD), there is a lack of a method to prove this association.MethodsOf 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.ResultsTwenty-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.ConclusionsData 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.

Background Unlike perianal fistula, long‐term outcomes of nonperianal fistulae (NPF) in Crohn's disease (CD) are not clear. We aimed to compare the outcomes of medical and surgical therapies in patients with NPF. Methods We retrospectively analyzed the records of patients of CD with NPF who were prospectively followed from January 2005 to December 2018. Results Of the 53 patients with NPF [mean age at presentation:29 ± 14 years; 54.7% male; median duration of follow‐up: 47 months (interquartile range [IQR]:26–76 months)], enteroenteric fistula (37.8%) was the most common presentation. Of 22 patients treated with anti‐tumor necrosis factor (TNF) therapy, complete response was achieved in 40.9% (n = 9). Overall probability of maintaining response was similar between the anti‐TNF and surgical groups (95.2% vs 82.4%; 71% vs 76%; and 63% vs 69%% [P = 0.8] at 1, 2, and 3 years, respectively), with only 13.6% of patients treated with biologicals requiring surgery over 56 months. Twenty‐one patients required upfront surgery (small bowel or ileocolonic resection with/without diversion; 28.5% emergent), with 47.6% postoperative recurrence over 36 months, of which nine patients required biologicals (77.7% response to anti‐TNF therapy). Long‐term outcome was comparable between medically and surgically treated patients; 6.4% developed tuberculosis on anti‐TNF therapy. Two patients (3.7%) developed malignancy (one ‐ enteroenteric, one ‐ colovesical). Conclusion Anti‐TNF therapy appears to be as effective as surgery in this retrospective analysis of patients with NPFCD, and it may be indicated in the absence of abscess and other complications. These patients are at higher risk of fistula‐associated malignancy, which requires a lower threshold for suspicion, especially over the long term in the presence of nonresponse to medical therapy., This multicenter study evaluated the treatment outcomes and complications following surgery and anti‐tumor necrosis factor (TNF) therapy in patients with nonperianal fistulizing Crohn's disease (CD) and shows that both surgery and medical therapy are equally effectivea

H. pylori-associated gastritis in patients from the high-altitude area of Ladakh showed severe gastritis, mucosal nodularity, atrophy, and cancer in comparison to those from North India. This study served to analyze if differences in the H. pylori virulence genotypes decide the extent of gastric mucosal inflammation.Fifty gastric biopsies each from patients with H. pylori-associated gastritis from Ladakh and a tertiary care center in North India were included. The presence of H. pylori strain was confirmed with Warthin starry stain and polymerase chain amplification of the H. pylori-specific 16S rRNA. The cagA, vacA s1, s2, and m1, m2 alleles, and dupA virulence genotypes were studied in all archival samples, followed by their histological correlations.cagA (P 0.009) and vacAs1 m1 (P 0.009) genes were distinctly more in H. pylori strains colonizing the biopsies of North Indian patients. In contrast, the cagA -ve vacAs2 m2 strains were significantly more in H. pylori strain colonizing the biopsies from Ladakhi patients. dupA genotype was almost similarly present in strains from both regions. Among these, only cagA and dupA virulence genes were associated with severe mucosal neutrophilic activity and deep infiltration of H. pylori strains in North Indian patients.Differences in virulence genotypes of H. pylori in gastric biopsies from North Indian and Ladakhi patients were found not significant in deciding the severity of H. pylori-associated gastritis.

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.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.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%).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.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. \ud \ud \ud \ud Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). \ud \ud \ud \ud Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. \ud \ud \ud \ud Results: The median VH in NCGS was significantly shorter (600, IQR: 400–705) than controls (900, IQR: 667–1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390–620) vs. 427 µm (IQR: 348–569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. \ud \ud \ud \ud Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

Sarcopenia and visceral fat independently predict poor outcomes in Crohn's disease (CD). However, combined influence of these parameters on outcomes is unknown, and was investigated in the present study.This retrospective study evaluated skeletal muscle index (SMI-cross-sectional area of five skeletal muscles normalized for height), visceral and subcutaneous fat area and their ratio (VF/SC) on single-slice computed tomography (CT) images at L3 vertebrae in CD patients (CT done: January 2012-December 2015, patients followed till December 2019). Sarcopenia was defined as SMI 36.5 cmForty-four patients [age at onset: 34.4 ± 14.1 years, median disease duration: 48 (24-95) months, follow-up duration: 32 (12-53.5) months, males: 63.6%] were included. Prevalence of sarcopenia was 43%, more in females, but independent of age, disease severity, behavior and location. More patients with sarcopenia underwent surgery (31.6% vs 4%, p = 0.01). VF/SC was significantly higher in patients who underwent surgery (1.76 + 1.31 vs 0.9 + 0.41, p = 0.002), and a cutoff of 0.88 could predict surgery with sensitivity and specificity of 71% and 65% respectively. On survival analysis, probability of remaining free of surgery was lower in patients with sarcopenia (59.6% vs 94.1% p = 0.01) and those with VF/SC 0.88 (66.1% vs 91.1%, p = 0.1), and still lower in those with both sarcopenia and VF/SC 0.88 than those with either or none (38% vs 82% vs 100%, p = 0.01).Combination of sarcopenia and high visceral fat predict worse outcomes in CD than either.

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

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

Perianal fistula is one of the most challenging complications of Crohn’s disease (CD). We aimed to describe treatment response with surgical and medical therapies, and long-term complications. We retrospectively analyzed records of patients with perianal fistulizing CD who were prospectively followed from January 2005 to December 2018. Among 807 patients, 81 (10%) had perianal fistula and 65 were included in the final analysis. The mean age of presentation was 27.4 ± 10.3 years, and 78.5% were males with a median duration of follow-up of 45 (IQR, 24–66) months. 75.4% (n = 49) had complex fistulae. 55.4% (n = 36) of patients received multiple courses (> 5 courses) of antibiotics. Complete response rates with immunomodulators, fistula surgery, biologicals, and diversion were 25%, 42.8%, 39.5%, and 45.4%, respectively. The relapse rate was highest after fistula surgery (52.6%). 44.6% of patients received medical (immunomodulators—21 and biologicals—8) whereas 46.1% received surgery as the first-line therapy. The absence of perianal abscess was associated with complete fistula closure. One patient developed malignancy and 4 (6.1%) died at the end of follow-up. Among the patients (n = 28) who received biologicals, TB reactivation occurred in one patient (3.5%). Medical therapy should be offered as first-line therapy, and immunomodulators can be considered when patients cannot afford biologicals. Surgery offers temporary improvement and is associated with high relapse rates. Absence of perianal abscess predicts long-term complete fistula closure.

BACKGROUND AND AIM Although the gut microbiome of patients with ulcerative colitis (UC) has been characterized, no study has characterized the gut microbiome in acute severe colitis (ASC). We compared the gut microbiome of patients with UC, ASC, and healthy controls (HCs). METHODS Patients with mild to moderate UC (n = 24), ASC (n = 19 with 21 episodes) and HCs (n = 50) were recruited prospectively. A 16SrDNA amplicon approach was used to explore gut microbial diversity and taxonomic repertoires. UC was diagnosed using European Crohn's and Colitis Organization guidelines, and ASC was diagnosed using Truelove and Witts' criteria. RESULTS The normalized alpha diversity was significantly lower in ASC than mild-moderately active UC (P

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

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%; I2 = 86%) and 9.7% (95% CI 2.7-20.2%; I2 = 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%; I2 = 76%) and 11.6% (95% CI 4.1-22.2%; I2 = 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.

The decision to withdraw anti-tumor necrosis factor (anti-TNF) therapy in patients with inflammatory bowel disease (IBD) remains controversial, especially in the developing world, where its long-term use is restrained by side effects and prohibitive cost. Present study evaluated the relapse rate and its predictors following anti-TNF withdrawal in a cohort of IBD patients from northern India. Patients with IBD who received anti-TNF therapy (induction and beyond), and were under follow-up at All India Institute of Medical Sciences, New Delhi, from January 2005 to July 2018 were included. Demographic features, disease characteristics, duration, response to anti-TNF therapy, and relapse rate after its withdrawal were analyzed. Among 4600 patients with IBD under follow-up, 90 (1.9%) received anti-TNF therapy, of whom 11 were excluded (8—complete records unavailable; 3—received only single dose). Of 79 patients (mean age—40.1 ± 14.2 years; 53.2% males; 31 [39.2%] ulcerative colitis, 47 [59.5%] Crohn’s disease; median follow-up—24 [12–39] months), 9 (11.4%) were primary non-responders, 19 (24.1%) had secondary loss of response, and 51 (64.5%) maintained clinical response on anti-TNF. Anti-TNF was withdrawn in 45 (57%) patients (major causes: financial burden—16.5%; tubercular reactivation—12.7%), of whom 33 were in clinical remission. Over a median follow-up of 26 (7.5–45) months, 15 patients (45.5%) relapsed. Most of them responded to antibiotics, steroids, or anti-TNF agents; only 3 required surgery. On Kaplan-Meier analysis, long disease duration prior to therapy was a significant predictor of relapse (hazard ratio [HR] = 1.33, p = 0.034). Almost 50% patients with IBD in clinical remission relapse within a year of anti-TNF withdrawal. However, most of these patients have a favorable disease course and respond to medical therapy.