Background/Aims: Evidence on predictors of primary nonresponse (PNR), and secondary loss of response (SLR) to anti-tumor necrosis factor (anti-TNF) agents in inflammatory bowel disease is scarce from Asia. We evaluated clinical/biochemical/molecular markers of PNR/SLR in ulcerative colitis (UC) and Crohn’s disease (CD). Methods: Inflammatory bowel disease patients treated with anti-TNF agents (January 2005–October 2020) were ambispectively included. Data concerning clinical and biochemical predictors was retrieved from a prospectively maintained database. Immunohistochemistry for expression of oncostatin M (OSM), OSM receptor (OSM-R), and interleukin-7 receptor (IL-7R) were done on pre anti-TNF initiation mucosal biopsies. Results: One-hundred eighty-six patients (118 CD, 68 UC: mean age, 34.1±13.7 years; median disease duration at anti-TNF initiation, 60 months; interquartile range, 28–100.5 months) were included. PNR was seen in 17% and 26.5% and SLR in 47% and 28% CD and UC patients, respectively. In CD, predictors of PNR were low albumin (P<0.001), postoperative recurrence (P=0.001) and high IL-7R expression (P<0.027) on univariate; and low albumin alone (hazard ratio [HR], 0.09; 95% confidence interval [CI], 0.03–0.28; P<0.001) on multivariate analysis respectively. Low albumin (HR, 0.31; 95% CI, 0.15–0.62; P=0.001) also predicted SLR. In UC, predictors of PNR were low albumin (P<0.001), and high C-reactive protein (P<0.001), OSM (P<0.04) and OSM-R (P=0.07) stromal expression on univariate; and low albumin alone (HR, 0.11; 95% CI, 0.03–0.39; P=0.001) on multivariate analysis respectively. Conclusions Low serum albumin at baseline significantly predicted PNR in UC and PNR/SLR in CD patients. Mucosal markers of PNR were high stromal OSM/OSM-R in UC and high IL-7R in CD patients.

Background/Aims: Intestinal tuberculosis (ITB) and Crohn’s disease (CD) frequently present with a diagnostic dilemma because of similar presentation. Interferon-gamma release assay (IGRA) has been used in differentiating ITB from CD, but with sparse reports on its diagnostic accuracy in tuberculosis endemic regions and this study evaluated the same. Methods: Patients with definitive diagnosis of ITB (n=59) or CD (n=49) who underwent IGRA testing (n=307) were retrospectively included at All India Institute of Medical Sciences, New Delhi (July 2014 to September 2021). CD or ITB was diagnosed as per standard criteria. IGRA was considered positive at >0.35 IU/mL.Relevant data was collected and IGRA results were compared between ITB and CD to determine its accuracy. Results: Among 59 ITB patients (mean age, 32.6±13.1 years; median disease duration, 1 year; male, 59.3%), 24 were positive and 35 tested negative for IGRA. Among 49 CD patients (mean age, 37.8±14.0; median disease duration, 4 years; male, 61.2%), 12 were positive and 37 tested negative for IGRA. Hence, for diagnosing ITB, IGRA showed a sensitivity, specificity, positive and negative predictive values of 40.68%, 75.51%, 66.67%, and 51.39%, respectively. The area under the curve of IGRA for ITB diagnosis was 0.66 (95% confidence interval, 0.55–0.75). In a subset (n=64), tuberculin skin test (TST) showed sensitivity, specificity, positive and negative predictive values of 64.7%, 73.3%, 73.3%, and 64.71%, respectively. IGRA and TST were concordant in 38 (59.4%) patients with κ=0.17. Conclusions In a tuberculosis endemic region, IGRA had poor diagnostic accuracy for differentiating ITB from CD, suggesting a limited value of IGRA in this setting.

Background/Aims: Existing therapeutic options for complicated Crohn’s disease (CD) like biologics and surgery are limited by inadequate long-term efficacy, cost, and adverse effects. Tissue hypoxia is important in CD pathogenesis and may be ameliorated with hyperbaric oxygen therapy (HBOT). We assessed the efficacy and tolerability of HBOT in small bowel stricturing CD. Methods: This pilot study included patients of small bowel stricturing CD (from April 2019 to January 2020) who underwent HBOT. These patients were refractory to conventional medical treatment or had multiple strictures not amenable to resection. Each session of HBOT was given for 60 minutes with a pressure of 1.5–2.5 atm. Clinical, biochemical responses and Short Inflammatory Bowel Disease (SIBD) questionnaire were evaluated at 2 and 6 months, and radiological response was evaluated at 6 months. Results: Fourteen patients (mean age, 42.9±15.7 years; male, 50%) were subjected to 168 HBOT sessions. Thirteen patients (92.7%) had strictures and 1 patient had enterocutaneous fistula in addition. Median number of HBOT sessions was 11 (range, 3–20) which were administered over a median of 4 weeks. Most patients tolerated it well except 1 who had hemotympanum. At 2 and 6 months of follow-up, 64.2% of patients had a clinical response, 50% and 64.2% of patients had clinical remission respectively. Steroid-free clinical remission was seen in 8 (57%) of patients with radiological improvement in 50%. There was a significant improvement in SIBD scores at 2-month follow-up (59.4 vs. 44.5, P=0.03). Conclusions HBOT can be a safe and effective therapeutic option in patients with stricturing small bowel CD refractory to conventional medical treatment.

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.

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.

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.

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.
Biopsy ; Celiac Disease ; Classification ; Cohort Studies ; Epithelial Cells ; Humans ; Intestine, Small ; Logistic Models ; Lymphocyte Count ; Observer Variation ; Sensitivity and Specificity

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.
Adalimumab ; Asia ; Asian Continental Ancestry Group ; Biological Factors ; Biosimilar Pharmaceuticals ; Colitis ; Colitis, Ulcerative ; Consensus ; Cooperative Behavior ; Crohn Disease ; Gastroenterology ; Hepatitis B ; Humans ; Immunologic Factors ; Inflammatory Bowel Diseases ; Infliximab ; Pharmacogenetics ; Philippines ; Practice Guidelines as Topic ; Tuberculosis ; Ulcer

BACKGROUND/AIMS: Celiac disease is a global health problem. The presentation of celiac disease has unfolded over years and it is now known that it can manifest at different ages, has varied presentations, and is prone to develop complications, if not managed properly. Although the Oslo definitions provide consensus on the various terminologies used in literature, there is no phenotypic classification providing a composite diagnosis for the disease. METHODS: Various variables identified for phenotypic classification included age at diagnosis, age at onset of symptoms, clinical presentation, family history and complications. These were applied to the existing registry of 1,664 patients at Dayanand Medical College and Hospital, Ludhiana, India. In addition, age was evaluated as below 15 and below 18 years. Cross tabulations were used for the verification of the classification using the existing data. Expert opinion was sought from both international and national experts of varying fields. RESULTS: After empirical verification, age at diagnosis was considered appropriate in between A1 ( < 18) and A2 (≥18). The disease presentation has been classified into 3 types–P1 (classical), P2 (non-classical) and P3 (asymptomatic). Complications were considered as absent (C0) or present (C1). A single phenotypic classification based on these 3 characteristics, namely age at the diagnosis, clinical presentation, and intestinal complications (APC classification) was derived. CONCLUSIONS: APC classification (age at diagnosis, presentation, complications) is a simple disease explanatory classification for patients with celiac disease aimed at providing a composite diagnosis.
Age of Onset ; Celiac Disease* ; Classification* ; Consensus ; Diagnosis ; Expert Testimony ; Global Health ; Humans ; India