Inflammatory Bowel Disease In India Research Articles

DOP30 Cross-ethnic microbiome analyses identify shared and specific signals for Northern Indian IBD patients

Abstract Background Clinical manifestation of the inflammatory bowel disease (IBD) shows considerable variation across the world. We hypothesized these differences may be influenced by geographical differences in gut microbiome. To test this, we investigated the correlation between gut microbiota and the disease phenotypes of IBD in a cohort form the Northern part of India. Methods Stool samples and clinical metadata were collected from 226 IBD patients (198 ulcerative colitis and 28 Crohn’s disease) and 66 controls from a population cohort from the Northern India. We used metagenomic shotgun sequencing to determine diversity, composition and function of the gut microbiota of the participants. Microbiome was then associated to IBD and its subtypes and clinical metadata (e.g. medication use, drug response, and disease activity). We replicated our results in 436 IBD patients and 903 population controls from the Netherlands analyzed using an identical workflow and used machine learning to assess how well do the Indian IBD signals generalize to Dutch IBD. Results We identified reduction in microbiome diversity and changes in beta diversity in Indian IBD patients (FDR < 0.05, replicated in Dutch population) and identified that 319 taxa and 71 biochemical pathways are altered in Indian patients (FDR < 0.05). Of note, 39% of these signals were replicated in the Dutch cohort (at FDR < 0.05 level). We identified strong dysbiosis shared across Indian and Dutch IBD patients, characterized by expansion of opportunistic pathogens (e.g. Genera Clostridium, Streptococcus and Lactobacilli) and oral bacteria (e.g. Streptococcus oralis and Bifidobacterium dentium) as well as reduction in butyrate producers such as Faecalibacterium prausnitzii, Roseburia hominis and Blautia massiliensis. In addition, we found novel pathobionts specific to the Indian cohort (including oral bacteria from Genus Scardovia and Oribacterium; Actinomyces dentalis and Klebsiella pneumoniae). Machine-learning models trained on the Indian cohort were highly predictive in the Indian test set (Sensitivity 0.84, Specificity 0.95) and generalized to Dutch cohort (Sensitivity 0.77, Specificity 0.69). In addition to IBD-associated dysbiosis, we identified links between medication use and gut microbiota independent of the disease activity: use of Tofacitinib (used by 26 UC patients) was linked to decrease in Lactobacilliales and increase in Clostridia, while Prednisolone and Azathioprine associated to reduction in Roseburia and increase in Streptococcus and Granulicatella. Conclusion The IBD patients from Northern India show gut dysbiosis similar to European patients, but also show enrichment in India-specific pathobionts. The microbiome-based diagnostic models generalize across these populations.

Depression and active disease are the major risk factors for fatigue and sleep disturbance in inflammatory bowel disease with consequent poor quality of life: Analysis of the interplay between psychosocial factors from the developing world.

The prevalence and risk factors of fatigue and sleep disturbances in inflammatory bowel disease (IBD) patients and their impact on the quality of life (QOL) are largely underreported in the developing world, where IBD is on the rise. Consecutive patients attending the IBD clinic were interviewed between November 2021 and March 2022 using an assisted questionnaire (English, Hindi and Telugu versions)(including demographics, disease activity, QOL, IBD fatigue score [IBD-F], Hospital anxiety and depression score: [HADS], Pittsburg Sleep Quality Index: [PSQI]). Logistic regression was used to identify risk factors of fatigue and sleep disturbance. A correlational analysis between mental health factors and QOL was performed. AS many as 202 IBD patients (age 18-78 [median 31] years, 65.8% male) completed the questionnaires. Fatigue and sleep disturbances were highly prevalent (55.9% and 53.4%, respectively). On multi-variate analysis, depression (p = 0.008, odds ratio [OR] -1.38, 95% confidence interval [CI]-1.09-1.75), active disease (p = 0.001,OR-8.81,95% CI- 2.49-31.23) and poor sleep (p = 0.009, OR-1.17, 95% CI:1.04-1.31) were predictive of fatigue, whereas depression (p < 0.001,OR-1.32,95% CI-1.19-1.46) and active disease (p < 0.001,OR-6.77, 95% CI-2.67-17.17) were predictive of sleep disturbance. On sub-group analysis, poor sleep quality and lack of renumeration predicted fatigue, whereas old age and female gender predicted poor sleep quality in Crohn's disease (CD). QOL (Short IBD questionnaire: [SIBDQ]) scores had a strong and moderate negative correlation with IBD-F (r = -0.735, p < 0.0001) and PSQI (r = -0.682, p < 0.001) scores, respectively. The results should be interpreted in the context of lack of validated translated questionnaires in all native languages in a multilingual country. Translational assistance was provided to overcome the limitation. Fatigue and sleep disturbances are highly prevalent in Indian IBD patients. Apart from modulation of disease activity, screening those with mental health illness may help improve fatigue/sleep quality and overall QOL.

Trends of inflammatory bowel disease from the Global Burden of Disease Study (1990-2019).

The global burden of inflammatory bowel disease (IBD) is reportedly increasing. Methodologies and datasets are routinely updated, allowing for more accurate estimates to guide healthcare policy. The Global Burden of Diseases, Injuries and Risk Factors Study (GBD) dataset was accessed and the trends in IBD at the global and regional levels from 1990 to 2019 were estimated for incidence, prevalence, deaths, years of life lost (YLL), years lived with disability (YLD) and disability-adjusted life-years (DALYs) per 100,000 population. The three decadal trends of the disease measures were calculated. In 2019, there were 4.9 million (95% Uncertainty Interval [UI] 4.3-5.5) cases of IBD globally. The age-standardized prevalence and incidence rates decreased from 73.23 (95% UI 63.8-83.6) and 6.1 (95% UI 5.3-6.9) in 1990 to 59.2 (95% UI 52.7-66.4) and 4.9 (95% UI 4.4-5.6) in 2019, respectively. Like prior estimates, the highest age-standardized prevalence and incidence rates occurred in North America, but the lowest rates were reported in Oceania (209.5[195.4-224.4] and 24.5[22.6-26.7] and 3.87[3.1-4.7] and 0.5[0.5-0.7], respectively) and not the Caribbean, as previously reported. High socio-demographic index (SDI) locations had the highest age-standardized prevalence rate, though the rates declined in 2019 compared to 1990. The age-standardized prevalence and incidence rates increased in middle, low middle and low SDI quintiles over the three decades. The age-standardized rates for deaths, DALYs, YLD and YLL decreased globally from 1990 to 2019. Between 1990 and 2019 the total number of patients with IBD in India doubled from 0.13 million (95% UI 0.10-0.16) to 0.27 million (95% UI 0.21-0.33) with age-standardized incidence rate increasing from 2.23 (95% UI 1.85-2.73) to 2.34 (95%UI 1.95-2.86). This analysis of the GBD 2019 database demonstrates that the overall global burden of IBD is lower than previously estimated, but an increasing disease burden is observed in the middle and low-SDI locations.

Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India.

Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.

A Review on Prevalence of Inflammatory Bowel Disease in India

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn’s disease (CD) was believed to be a Western disease, but are now increasingly being reported from India and other Asian countries where IBD was almost unheard of 30 years ago. Now India is projected to have one of the highest IBD burden across the world. There is rising incidence and prevalence of IBD in India topping the Southeast Asian countries. The clinical presentation of IBD in India is similar to other South East Asian countries. IBD is considered as a result of the complex interaction between the environment, diet, certain medications, genetic variables and a severe autoimmune response against normal bacteria in the gut. However exact cause is still unknown. Also there exists a gender distribution in IBD. In India IBD is more prevalent in males compared to females. This review summarizes the prevalence of IBD in India and some possible risk factors contributing to it.&#x0D; Keywords: Inflammatory bowel disease, prevalence, India

Clinical spectrum of elderly-onset inflammatory bowel disease in India.

Inflammatory bowel disease (IBD) is increasingly being recognized in elderly patients. Data on clinical spectrum of elderly-onset IBD patients is lacking from India. A cross-sectional retrospective analysis of a prospectively maintained database of patients diagnosed with IBD was conducted at 2 centers in India. The clinical spectrum of elderly-onset IBD including demographic profile (age and sex), clinical presentation, disease characteristics (disease behavior and severity, extent of disease), and treatment were recorded and compared with adult-onset IBD. During the study period, 3,922 (3,172 ulcerative colitis [UC] and 750 Crohn's disease [CD]) patients with IBD were recorded in the database. A total of 186 patients (4.74%; 116 males [62.36%]) had elderly-onset IBD (69.35% UC and 30.64% CD). Diarrhea, blood in stools, nocturnal frequency and pain abdomen were the commonest presentations for UC, whereas pain abdomen, weight loss and diarrhea were the most frequent symptoms in CD. For both elderly onset UC and CD, majority of the patients had moderately severe disease. Left-sided colitis was the commonest disease location in UC. Isolated ileal disease and inflammatory behavior were the most common disease location and behavior, respectively in CD. 5-Aminosalicylates were the commonest prescribed drug for both elderly onset UC and CD. Thiopurines and biologics were used infrequently. Prevalence of colorectal cancer was higher in elderly onset IBD. Elderly onset IBD is not uncommon in India. Both the elderly onset UC and CD were milder, with no significant differences in disease characteristics (disease extent, location and behavior) when compared to adult-onset IBD. Colorectal cancer was more common in elderly onset IBD.

P392 To study the prevalence of depression and anxiety in patients of Inflammatory Bowel Disease (IBD) and the efficacy of psychopharmacotherapy in these patients: A pilot study

Abstract Background There is high prevalence of psychiatric disorders amongst IBD patients which independently affect quality of life. Studies have shown psychological stress leads to IBD flare. Non pharmacological psychotherapy has been studied in treatment of IBD, but not psychopharmacotherapy. We feel treatment for mental disorders in IBD patients may improve outcomes. Methods This is a prospective, observational single centre pilot study. After ethics committee approval, 200 patients were accrued between November, 2019 &amp; June, 2021, with, 1 year follow up for patients with anxiety or depression. All patients &amp;gt;18 years with Ulcerative Colitis (UC)/Crohn’s disease (CD) were enrolled. We excluded patients with IBD-Unclassified, post ileostomy/colostomy, on biologicals, malignancy. For assessing disease activity in UC we used UCEIS &amp; pMAYO scores; CDEIS &amp; Harvey-Bradshaw scores for CD. HADS-A &amp; HADS-D scores were used to determine anxiety and depression, respectively. Patient with HADS-A or HADS-D &amp;gt;, 7 were considered to have significant anxiety/depression, were given psychopharmacotherapy as per psychiatrist. All patients received IBD therapy as per standard of care. These patients were followed up at, 3, 6, 9 and, 12 months to assess the clinical parameters and HADS scores at each visit. Colonoscopy was repeated after a year to assess endoscopic activity. Results In our pilot study of, 200 patients CD was seen in, 84 (42.0%) &amp; UC in, 116 (58.0%). Prevalence of Anxiety was, 15%, Depression, 7% &amp; pooled prevalence, 22%., 86 patients (43.0%) received only IBD therapy., 66 (33.0%) received, 1 antipsychotic drug, 33 received, 2 (16.5%), 15 (7.5%) were prescribed, 3. Patients receiving psychopharmacotherapy, showed significant improvement in HADS-A or HADS-D scores at, 3, 6,9 and, 12 months. Amongst patients with UC, there was a significant improvement in UCEIS score (4.73 to, 2.36) in patients who received psychopharmacotherapy in addition to IBD standard of care after, 1 year (p&amp;lt;0.05). Similarly, the mean p-MAYO score dropped from, 4.91 to, 2.17 in patients receiving psychopharmacotherapy (p&amp;lt;0.05). The same pattern was observed in patients with Crohn’s disease receiving psychopharmacotherapy, in whom the mean CDEIS score dropped from, 5.43 to, 2.16 after, 1 year. Also, the mean Harvey-Bradshaw score dropped from, 5.57 to, 2.86. Both in UC &amp; CD; clinical, endoscopic scores significantly improved in patients who were given psychopharmacotherapy in addition to SOC. Conclusion Our study confirmed the high prevalence of anxiety and depression amongst Indian IBD patients. IBD patients with significant anxiety or depression benefit from Psychopharmacotherapy in addition to standard of care treatment, showed improvement in clinical as well as endoscopic disease activity.

Comparison of Oral Prednisolone, Budesonide and Probiotics in the Treatment of Canine Inflammatory Bowel Disease

Background: Inflammatory bowel disease (IBD) is the common cause of chronic gastrointestinal signs in dogs. The treatment possesses numerous difficulties due to the idiopathic nature of the disease. Conventional steroid therapy usually produces side effects on long term usage. Thus, there is a need for alternative therapies. When compared to human medicine, there is no published data on the use of budesonide and probiotic in the treatment of canine IBD in India. The present study was proposed to compare oral prednisolone, budesonide and probiotics in the management of canine inflammatory bowel disease. Methods: Thirty dogs with idiopathic IBD were selected and randomly grouped. They were subjected to therapy involving prednisolone, budesonide or probiotics. Clinical assessment was performed by calculation of the post treatment Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) score, faecal score and endoscopy. Biochemical analysis of alkaline phosphatase and alanine transaminase were done to record side effects of steroid administration. Result: It was observed from the present study that both prednisolone and budesonide are equally effective in the management of IBD in dogs. Probiotics were found to be less effective when compared to prednisolone and budesonide in the treatment of IBD.

Impact of Demographic, Clinical and Psychosocial Variables on Drug Adherence and Outcomes in Indian Patients With Inflammatory Bowel Disease: Cost is not the Only Factor!

Barriers to drug adherence in the developing world are multifactorial and under evaluated. We aimed to evaluate predictive factors of medication adherence in Indian patients with inflammatory bowel disease (IBD) and association of adherence with quality of life (QOL) and relapse free remission. Adherence was assessed in consecutive IBD patients using a self-administered survey questionnaire including Morisky Medication Adherence Scale together with interview and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) to assess QOL. Logistic regression analysis was used to identify variables correlating with adherence, Cox proportional hazards method used for variables associated with relapse and Kaplan-Meier survival curve used for comparing relapse free remission in adherent and nonadherent. A total of 467 consecutive outpatients (279 ulcerative colitis, 188 Crohn's disease, mean age 38.6 y) were mostly on mesalazine 439 (94%) or thiopurines 213 (46%). Self-reported nonadherence was noted in 236/467 (51%). Disease remission was associated with medication adherence [P=0.003, odds ratio (OR): 1.75, 95% confidence interval (CI): 1.21-2.52]. Medication-related factors like high dosing frequency (>3/d) (OR: 0.39, P=0.005) and concomitant non-IBD medications (OR: 0.44, P=0.007) were associated with nonadherence. Psychosocial factors associated with nonadherence were lack of drug information (OR: 0.30, P<0.001), feeling depressed (OR: 0.43, P<0.001), comorbidities (OR: 0.47, P=0.005), doubts about efficacy (OR: 0.49, P=0.001) and perceived poor QOL (OR: 0.61, P=0.01). High-cost perception was associated with nonadherence in univariate analysis (OR: 0.47, P<0.001) but lost significance on multivariate analysis (OR: 0.68, P=0.07). Physician imparting disease information (OR: 2.5, P=0.14) and physician reinforcement (OR: 1.8, P=0.049) were associated with adherence.Adherence was associated with improved QOL (SIBDQ, R=0.724). Nonadherence was associated with >3-fold risk of recurrence within 2 years (hazard ratio: 3.89, 95% CI: 2.74-5.52, P<0.001). Nonadherence is common in Indian IBD patients but adherence is associated with improved QoL and lower probability of relapse. Psychosocial and medication-related factors are important determinants of adherence compared with demographic or clinical variables and should be addressed.

S0677 An Indian National Survey of Gastroenterologists' Views on Dysplasia Surveillance and Chromoendoscopy in IBD

INTRODUCTION: International societal guidelines support use of chromoendoscopy (CE) for dysplasia surveillance in patients with inflammatory bowel disease (IBD). Our objective was to assess current dysplasia surveillance practices among gastroenterologists in India, which has the second highest number of patients with IBD after the USA. METHODS: A 31-question survey was distributed to members of the Indian Society of Gastroenterology. RESULTS: A total of 128 participated (94.5% male) with 87.5% consultant gastroenterologists (GI), 6.25% clinicians with GI interest & 6.25% GI trainees. Of these, 117 (91.4%) participants agreed that IBD patients in India require colonoscopic surveillance, 100 (78.2%) carried out surveillance colonoscopies. The 3 most common reasons for not performing IBD surveillance were lack of local guidelines (78.6%), cost constraints (78.6%) and perceived low-risk of colorectal cancer from IBD in Indians compared to the West (75%). Information on the practice of surveillance colonoscopy was available for 89/100 (89%). The preferred surveillance modality was standard white light endoscopy (WLE) by 38.2%, high definition WLE by 24.7%, narrow band imaging by 27% & dye-based (DB) chromo-endoscopy (CE) by 10.1%. 41.6% did not feel confident using CE, 44.9% felt confident using dye-less CE and 16.8% were confident of using DB CE. Random biopsies were considered an effective method of detecting neoplasia by 41 (46.1%) 65 (73%) were aware of recommendations from major organisations endorsing use of CE over random biopsies. The average number of biopsies performed at surveillance was 13 (median 10, IQR 10.25) with 16.7% performing quadrantic biopsies at 10 cm intervals in >50% of patients. The biggest barrier considered for using newer endoscopic modalities was financial constraints (77.1%) and 69.9% felt patients would receive better care with availability of novel endoscopic tools. The need for local IBD dysplasia surveillance guidelines was suggested by 79.8%. CONCLUSION: We noted a high level of awareness regarding dysplasia surveillance but considerable variation in practice amongst GI clinicians in India. Cost constraints and lack of local guidelines were deemed significant barriers for modern dysplasia surveillance. The rising incidence and prevalence of IBD in India emphasises an urgent need for training and pragmatic guidelines to improve surveillance strategies.

Paediatric inflammatory bowel disease in India: a prospective multicentre study.

Paediatric inflammatory bowel disease (PIBD) is increasing across the world. However, information from India is sparse. This multicentre study evaluated the demographics, clinical phenotype and outcome of PIBD from India. Data of children (≤18 years) with PIBD were collected using a proforma containing details of demographics, clinical profile, extraintestinal manifestations (EIM), investigations, disease extent and treatment. Three hundred twenty-five children [Crohn's disease: 65.2%, ulcerative colitis: 28.0%, IBD unclassified (IBDU): 6.7%, median age at diagnosis: 11 (interquartile range 6.3) years] were enrolled. 6.9% children had family history of IBD. Pancolitis (E4) was predominant in ulcerative colitis (57.8%) and ileocolonic (L3, 55.7%) in Crohn's disease. Perianal disease was present in 10.9% and growth failure in 20.9% of Crohn's disease cases. Steroids were the initial therapy in 84.2%, 5-amino salicylic acid in 67.3% and exclusive enteral nutrition (EEN) in 1.3% cases. Overall, immunomodulators and biologics were given to 84.3 and 17.9% cases, respectively, and 2.9% cases underwent surgery. Very early onset IBD (VEOIBD) was seen in 60 (19.2%) children. IBDU was commoner in the VEOIBD than the older-PIBD (18/60 vs 4/253; P < 0.001). VEOIBD-Crohn's disease patients more often had isolated colonic disease than the older Crohn's disease (45.4% vs 11.8%; P < 0.001). Prevalence of perianal disease, EIM, therapeutic requirements and outcome were not different between VEOIBD and older-PIBD. Disease location and phenotype of PIBD in Indian children is similar to the children from the west. However, the therapeutic options of EEN, biologics and surgery are underutilized. VEOIBD accounted for 19.2% of PIBD.

Colitis and Crohn's Foundation (India): a first nationwide inflammatory bowel disease registry.

Background/AimsThe national registry for inflammatory bowel disease (IBD) was designed to study epidemiology and prescribing pattern of treatment of IBD in India.MethodsA multicenter, cross-sectional, prospective registry was established across four geographical zones of India. Adult patients with ulcerative colitis (UC) or Crohn’s disease (CD) were enrolled between January 2014 and December 2015. Information related to demographics; disease features; complications; and treatment history were collected and analyzed.ResultsA total of 3,863 patients (mean age, 36.7 ± 13.6 years; 3,232 UC [83.7%] and 631 CD [16.3%]) were enrolled. The majority of patients with UC (n = 1,870, 57.9%) were from north, CD was more common in south (n = 348, 55.5%). The UC:CD ratio was 5.1:1. There was a male predominance (male:female = 1.6:1). The commonest presentation of UC was moderately severe (n = 1,939, 60%) and E2 disease (n = 1,895, 58.6%). Patients with CD most commonly presented with ileocolonic (n = 229, 36.3%) inflammatory (n = 504, 79.9%) disease. Extraintestinal manifestations were recorded among 13% and 20% of patients in UC and CD respectively. Less than 1% patients from both cohorts developed colon cancer (n = 26, 0.7%). The commonly used drugs were 5-aminosalicylates (99%) in both UC and CD followed by azathioprine (34.4%). Biologics were used in only 1.5% of patients; more commonly for UC in north and CD in south.ConclusionsThe national IBD registry brings out diversities in the 4 geographical zones of India. This will help in aiding research on IBD and improving quality of patient care.

IBD in India: Similar Phenotype but Different Demographics Than the West.

Inflammatory bowel disease (IBD) is emerging in the developing world but phenotypic data are limited. We aimed to describe the phenotype, clinical presentation, disease behavior, and treatments of IBD in a large cohort in India. All persons presenting to the Asian Institute of Gastroenterology in Hyderabad, India since 2004 with a confirmed diagnosis of IBD were enrolled. The demographic profile at the first visit, family history of IBD, smoking history, time from first symptom onset to diagnosis, use of anti-tuberculousis treatment before IBD-specific treatment, disease phenotype, and medication history were collected by interview and chart review. Disease and family history and treatments used were updated at each follow-up visit. Of 4006 persons enrolled, 59.9% had ulcerative colitis (UC) and the majority were male (60.3%). The median diagnostic delay in both UC and Crohn's disease (CD) was at least 2 years. At the time of diagnosis only 4.5% of CD were smokers and only 3.8% of UC were ex-smokers. Positive family history was uncommon (2.1%). The phenotype of persons with CD included 22.9% with stricturing disease and 9.4% with fistulizing disease. The most common site of disease was ileocolonic (40.9%) and only 2.5% had perineal fistulas. Among those with UC 18.7% had proctitis and 30.3% had pancolitis. This is the largest cohort of persons with IBD reported from Asia. Although there are several demographic differences between persons with IBD from India compared with the West, the phenotypes of the disease are not highly different.

Familial aggregation of inflammatory bowel disease in India: prevalence, risks and impact on disease behavior.

Background/Aims Information about familial aggregation of inflammatory bowel disease (IBD) in Asia is limited. We aimed to analyze the prevalence and risk of familial IBD in an Indian cohort and compare familial and sporadic cases. Methods Familial IBD cases were identified from a large prospectively maintained IBD registry. The prevalence of IBD in first- and seconddegree relatives of index cases was evaluated. The disease behavior was compared to that of sporadic cases. Results Total 3,553 patients (ulcerative colitis [UC], 2,053; Crohn’s disease [CD], 1,500) were included. Familial IBD was noted in 4.13% of CD and 4.34% of UC patients. Family history was commoner in pediatric group (< 18 years) (P= 0.0002; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6–4.8). Majority had paternal transmission (UC, 67.42%; CD, 70.97%). Concordance of disease type was higher in UC (79.7%) compared to CD (37.1%). Familial IBD was associated with higher cumulative relapse rate (CD, P< 0.001; UC, P< 0.001), higher cumulative rate of surgery (CD, P< 0.001; UC, P< 0.001) and higher rate of biologic use (CD, P= 0.010; UC, P= 0.015). Pan-colitis was higher in familial UC (P= 0.003; OR, 1.935; 95% CI, 1.248–3.000). Fistulizing disease was commoner in familial CD (P= 0.041; OR, 2.044; 95% CI, 1.030–4.056). Conclusions The prevalence of familial IBD in India appears comparable to rest of Asia but lower than the West. It is associated with a younger age of onset, higher incidence of pan-colitis in UC and fistulizing complications in CD. Familial IBD has higher cumulative relapse, surgery and biologic use rates. Hence, family history of IBD could have important prognostic implications.

The challenge of inflammatory bowel disease in India

The challenge of inflammatory bowel disease in India

Sa1679 - Nudt15 Variant can Predict the Development of Azathioprine Induced Leucopenia and Allow Optimal Dosing in Indian Patients with Inflammatory Bowel Disease (IBD)

Background Azathioprine (AZA) is a widely used cost-effective option for maintenance of steroid-free remission of IBD. Leucopenia is a common complication. Recent GWAS studies have identified a strong association between NUDT 15 C415T variant and thiopurine-induced leucopenia in Asia. We assessed the prevalence of NUDT variant and its association with leucopenia and dosing of AZA in an Indian IBD cohort. Methods Prospectively collected data from our IBD Clinic Registry was analysed. 729 consecutive patients treated with AZA were included. The incidence of side effects, initial and maximum dose tolerated and discontinuation time was noted. Blood sample (at-80C) of these patients were retrieved from the biorepository. Age and sex matched group of healthy volunteers served as the control group. DNA was isolated (Qiagen) (n=729 AZA;179 controls). Genotyping of NUDT15C415T(rs116855232;p.R139C) carried out employing Taq-man probes on Real-time PCR(Step one-Life tech). The association of presence of risk variant of NUDT15 with the development of leucopenia, other side effects and maximum tolerated dosage was evaluated. Results 711/729 patients were included in the analysis (18 inadequate DNA). (IDDF2018-ABS-0269 Table1) There was no significant differences in the frequency of C/C, C/T and T/T genotypes of NUDT15p.R139C between AZA group (82.28%, 15.75%–1.97%) and control group (88.27%,11.73%–0%). 79/711 patients developed leucopenia (26/585 C/C; 42/112C/T; 11/14 T/T). Development of leucopenia was significantly higher in C/T and T/T compared to C/C (OR 15.609; CI 9.198–26.490) (table 1). The sensitivity (67.08%) and specificity (88.45%) for predicting AZA-induced leucopenia. C/T group discontinued treatment significantly earlier than C/C genotype. There was no incidence of hepatitis/pancreatitis in C/T and T/T groups and no significant difference in the mean dose tolerated wild (C/C) vs risk variant (C/T,T/T) carriers(1.33 mg/kg vs 1.196 mg/kg;p=0.014). Conclusions NUDT15 risk genotype frequency is around 15% in Indian population and can predict the development of leucopenia. The results suggest thiopurines should be avoided in homozygous T/T and low dose for C/T heterozygous genotypes. This has important implications for clinical practice and is a step towards personalised management of IBD.

Multi-center prospective survey of inflammatory bowel diseases in Kerala: More than 2000 cases.

Inflammatory bowel disease (IBD) is considered uncommon in Asia. The aim of this study was to document the demographic characteristics and clinical aspects of ulcerative colitis (UC) and Crohn's disease (CD) in Kerala, India. A survey of IBD in Kerala was performed. All gastroenterologists in the region were invited. From May 2013 to October 2015, data were collected in a standardized pro-forma. Forty-seven doctors in 34 centers contributed data. A total of 2142 patients were analyzed. This is the largest state-wide survey of IBD in India. Ulcerative colitis was diagnosed in 1112 (38 new), Crohn's disease in 980 (53 new), and 50 were unclassified (5 new). The district-wise distribution of IBD cases correlated with the District-wise Gross State Domestic Product (r= 0.69, p< 0.01). Three percent was below the age of 18. Patients with UC had more diarrhea (73% vs. 51%), bleeding PR (79% vs. 34%), and intermittent flares (35% vs. 13%) (all p< 0.01). Patients with CD had more abdominal pain (62% vs. 46%), weight loss (53% vs. 40%), fever (28% vs. 18%), and history of antituberculosis treatment (21% vs. 5%) (all p< 0.01). Compared to adults, children (below 18years) were more likely to have extensive UC (58% vs. 34%, p< 0.01) and unclassified IBD (15% vs. 2%, p< 0.01). Inflammatory bowel disease is common in Kerala, India. The disease characteristics of patients with IBD are almost similar to those from other parts of the country. Both UC and CD were seen in equal proportion in Kerala.

P716. A well-maintained inflammatory bowel disease (IBD) registry can help assess and optimise treatment for the local population: a 10-year experience in an Indian IBD registry cohort

P716. A well-maintained inflammatory bowel disease (IBD) registry can help assess and optimise treatment for the local population: a 10-year experience in an Indian IBD registry cohort

P154. Temporal relationship of pregnancy to long-term disease course and pregnancy and foetal outcomes: North Indian inflammatory bowel disease cohort study

P154. Temporal relationship of pregnancy to long-term disease course and pregnancy and foetal outcomes: North Indian inflammatory bowel disease cohort study

Inflammatory bowel disease in India - Past, present and future.

There is rising incidence and prevalence of inflammatory bowel disease (IBD) in India topping the Southeast Asian (SEA) countries. The common genes implicated in disease pathogenesis in the West are not causal in Indian patients and the role of “hygiene hypothesis” is unclear. There appears to be a North-South divide with more ulcerative colitis (UC) in north and Crohn’s disease (CD) in south India. IBD in second generation Indian migrants to the West takes the early onset and more severe form of the West whereas it retains the nature of its country of origin in migrants to SEA countries. The clinical presentation is much like other SEA countries (similar age and sex profile, low positive family history and effect of smoking, roughly similar disease location, use of aminosalicylates for CD, low use of biologics and similar surgical rates) with some differences (higher incidence of inflammatory CD, lower perianal disease, higher use of aminosalicylates and azathioprine and lower current use of corticosteroids). UC presents more with extensive disease not paralleled in severity clinically or histologically, follows benign course with easy medical control and low incidence of fulminant disease, cancer, complications, and surgery. UC related colorectal cancer develop in an unpredictable manner with respect to disease duration and site questioning the validity of strict screening protocol. About a third of CD patients get antituberculosis drugs and a significant number presents with small intestinal bleed which is predominantly afflicted by aggressive inflammation. Biomarkers have inadequate diagnostic sensitivity and specificity for both. Pediatric IBD tends to be more severe than adult. Population based studies are needed to address the lacunae in epidemiology and definition of etiological factors. Newer biomarkers and advanced diagnostic techniques (in the field of gastrointestinal endoscopy, molecular pathology and genetics) needs to be developed for proper disease definition and treatment.