Asian Ulcerative Colitis Research Articles

Histologic healing and clinical outcomes in ulcerative colitis.

Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

P630 Identification of specific cell subsets related to treatment response after anti-tumor necrosis factor use in Korean ulcerative colitis patients using single cell RNA sequencing: a preliminary study

Abstract Background The breakdown of the epithelial barrier and mucosal homeostasis plays an important role in the development of ulcerative colitis (UC). Recently, single-cell RNA sequencing (scRNA-seq) has been performed to better understand the gene expression patterns and the characteristics of cells in intestine of UC patients. However, there is a lack of studies focus on Asian UC patients. The aim of this preliminary study was to identify the relevant cellular subsets related to treatment response after anti-tumor necrosis factor (anti-TNF) use in Korean UC patients using scRNA-seq. Methods This prospective study was conducted two University hospitals in Korea. We performed scRNA-seq on sigmoid colon tissue samples collected from one healthy control and nine biologic naïve UC patients scheduled to use anti-TNF due to lack of response to conventional therapy. All mucosal biopsies from active moderate to severe UC were collected at baseline (n=9) and at 52 weeks follow-up after anti-TNF use (n=2), at which time treatment response was assessed. Treatment responder was defined as those with sustained clinical remission (a partial Mayo score of ≤2 with no subscore >1 and a rectal bleeding subscore of 0) at 52 weeks. Results After processing the scRNA-seq data, 13 clusters were discovered and cell clusters were annotated using colon marker gene. Among nine patients, two patients who underwent response evaluation at 52 weeks after anti-TNF use were treatment responder. The normalized proportion of cluster 1 (stem cell-like cluster) in 52 weeks follow-up tissue samples after anti-TNF use was shown to be decreased significantly (p-value=0.03) from that found in the disease tissue samples. A decrease in the proportion of cell cluster 1 from disease tissue samples’ initial average percentage (30.6%) down to an average of 4.8% in the follow-up tissue samples is quite substantial (p-value=0.03). This decrease signifies a notable change in the composition of this specific cell cluster post-anti-TNF treatment. Moreover, reaching a level close to that of the healthy tissue sample (2.7%) suggests a potential restoration of this cell cluster's proportion towards a healthier state (Figure 1). Conclusion In Korean UC patients, this information should be crucial in understanding the impact of anti-TNF treatment on the cellular composition or behavior of this stem cell-like cluster, suggesting a potential effect of anti-TNF treatment on this particular cell population.

P819 Histologic activity and clinical outcomes in Ulcerative Colitis

Abstract Background Microscopic inflammation persisting in ulcerative colitis (UC) patients with endoscopic remission (ER) may be associated with a higher risk of clinical relapse (CRL). Growing evidence suggests histologic remission (HR) improves clinical outcomes. Data from Asian UC patients is lacking. We hypothesize that achieving HR is associated with better clinical outcomes in Asian UC patients. Methods We performed a single-centre retrospective cohort study of UC patients in clinical remission (CR) who had a follow-up (‘index’) colonoscopy and minimum one-year follow-up post-colonoscopy. CR was defined as Simple Clinical Colitis Activity Index (SCCAI) ≤2. ER was defined as Mayo Endoscopic Sub-Score (MES) ≤1 at index colonoscopy. HR was defined as Nancy Index ≤1 at index colonoscopy. CRL was defined as either SCCAI>2 (sub-score >1 for stool frequency or rectal bleeding), medication escalation for active disease, hospitalisation for UC relapse or colectomy for refractory UC. Kaplan-Meier survival analysis was performed to evaluate clinical relapse-free survival post-colonoscopy. Univariate and multivariate regression analyses were performed to assess predictors of CRL. Results 169 consecutive UC patients who had undergone colonoscopy from 1 Jan 2000 to 30 Jul 2019 were assessed for eligibility. 100 patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients (80%) were in ER, with 20 patients having persistent endoscopic activity (Table 1). On follow-up, 41 patients (41%) experienced CRL, with 59 remaining in CR. Of 80 patients in ER, 34 (42.5%) had persistent histologic activity (Nancy Index ≥2) and 29 (36.3%) relapsed during the follow-up period (Table 2). Amongst patients in CR and ER, those with HR had lower CRL rate (26.1% vs 50%, p=.028) and longer clinical relapse-free survival (mean 46.1 vs 31.5 months, p=.015) than those with persistent histologic activity (Figure 1). On univariate and multivariate analysis of 100 patients in CR, HR was significantly associated with lower risk of CRL (Table 3). Conclusion Above and beyond CR and ER, achieving HR improves clinical outcomes in Asian UC patients. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.

Real-life effectiveness and safety of tofacitinib treatment in patients with ulcerative colitis: a KASID multicenter cohort study.

Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with ulcerative colitis (UC). However, the real-life data on tofacitinib in Asian UC patients are limited. To investigate the real-life effectiveness and safety of tofacitinib induction and maintenance treatment in Korean patients with UC. This was a retrospective study on patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission at week 52, defined as a partial Mayo score of ⩽2 with a combined rectal bleeding subscore and stool frequency subscore of ⩽1, was used as the primary outcome. Adverse events (AEs), including herpes zoster and deep vein thrombosis, were also evaluated. A total of 148 patients with UC were started on tofacitinib. Clinical remission rates of 60.6%, 54.9%, and 52.8% were reported at weeks 16, 24, and 52, respectively. Clinical response rates of 71.8%, 67.6%, and 59.9% were reported at weeks 16, 24, and 52, respectively. Endoscopic remission rates at weeks 16 and 52 were 52.4% and 30.8% based on the Mayo endoscopic subscore and 20.7% and 15.2% based on the UC endoscopic index of severity (UCEIS), respectively. A higher UCEIS at baseline was negatively associated with clinical response [adjusted odds ratio (aOR): 0.774, p = 0.029] and corticosteroid-free clinical response (aOR: 0.782, p = 0.035) at week 52. AEs occurred in 19 patients (12.8%) and serious AEs in 12 patients (8.1%). Herpes zoster occurred in four patients (2.7%). One patient (0.7%) suffered from deep vein thrombosis. Tofacitinib was an effective induction and maintenance treatment with an acceptable safety profile in Korean patients with UC. Real-life effectiveness and safety of tofacitinib treatment in Korean patients with ulcerative colitis Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa that usually presents with bloody diarrhea and abdominal pain. Tofacitinib is a small molecule that inhibits Janus kinase and has been reported to be effective in Western patients with UC. However, real-life data on the effectiveness of tofacitinib in Asian patients with UC are limited. To investigate the real-life effectiveness and safety of tofacitinib treatment in Korean patients with UC, we retrospectively analyzed the data of 148 patients with UC who received tofacitinib treatment at 12 hospitals in Korea between January 2018 and November 2020. Clinical remission (i.e. complete improvement of symptoms) was achieved in 60.6% and 52.8% of patients at weeks 16 and 52, respectively. Endoscopic remission was achieved in 52.4% and 30.8% of patients at weeks 16 and 52, respectively. A higher baseline score of the UC endoscopic index of severity, which is one of the endoscopic indices that evaluate the severity of inflammation of the colon, was negatively associated with clinical response (i.e. partial improvement of symptoms). Adverse events (AEs) including herpes zoster and deep vein thrombosis occurred in 19 patients (12.8%) and serious AEs occurred in 12 patients (8.1%). Our real-life study shows that tofacitinib is a clinically effective treatment for Korean patients with UC, and the incidence of AEs was also similar to those observed in other real-world studies.

Similar Clinical Outcomes of Early and Late Anti-TNF Initiation for Ulcerative Colitis: A Nationwide Population-Based Study.

PurposeThe optimal timing of anti-tumor necrosis factor (anti-TNF) initiation in patients with ulcerative colitis (UC) remains unclear. Very little is known about the clinical outcomes after the early versus late initiation of anti-TNF therapy, especially in Asian UC patients. Here we aimed to assess whether earlier anti-TNF treatment initiation results in favorable clinical outcomes in Korean UC patients.Materials and MethodsUsing the Korean National Health Insurance claims database, we studied patients who were diagnosed with UC and received anti-TNF therapy for more than 6 months between 2010 and 2016. Using a Cox proportional hazard model, clinical outcomes including colectomy, UC-related emergency room (ER) visits, UC-related hospitalizations, and the need for corticosteroids were compared between early (≤2 years of diagnosis) and late (>2 years of diagnosis) initiators of anti-TNF therapy.ResultsAmong 17167 UC patients, 698 patients who received anti-TNF therapy for more than 6 months were included (420 infliximab, 242 adalimumab, and 36 golimumab). Of the 698 patients, 299 (42.8%) initiated anti-TNF therapy within 2 years of diagnosis. There were no significant differences in the risk of colectomy [adjusted hazard ratio (aHR), 0.41; 95% confidence interval (CI), 0.04–3.90], ER visits (aHR, 0.98; 95% CI, 0.50–1.92), hospitalization (aHR, 0.76; 95% CI, 0.57–1.01), and corticosteroid use (aHR, 1.04; 95% CI, 0.71–1.50) between early and late initiators of anti-TNF therapy.ConclusionPatients receiving early anti-TNF therapy had similar clinical outcomes to those of late initiators, suggesting that early anti-TNF therapy initiation offers little benefit in patients with UC.

Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.

Background Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. Methods In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. Findings We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. Conclusion In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.

819 Comparing Efficacy and Adverse Effects of Biological Agents in South Asian Inflammatory Bowel Disease Patients Living in the United States to Caucasian American Patients

INTRODUCTION: The aim of this study was to compare the efficacy and adverse effects of biological therapies in South Asian patients with Crohn’s disease (CD) and ulcerative colitis (UC) living in the United States with those of a Caucasian American cohort. METHODS: The efficacy, reasons for therapy discontinuation, and adverse effects of biological therapies in 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive Caucasian American patients (245 CD and 163 UC). The reasons for biologic therapy discontinuation were classified as: financial barrier, clinician judgment based on disease remission, primary non-response, secondary non-response, adverse effects, and patient preference. Adverse effects for biologic agents were classified as injection site reaction, infusion reactions, cytopenia, secondary infections, neurologic effects (including demyelinating disease or vestibular issues), cardiac effects (including heart failure), cutaneous effects, malignancy, and others. RESULTS: For both the South Asian and Caucasian American cohorts, adalimumab and infliximab were the most commonly prescribed biologic agents. Twenty-two out of 22 (100%) South Asian CD patients treated with adalimumab or infliximab had primary response. The Caucasian American CD cohort had a primary non-response rate of 16.5% to adalimumab and 12.1% to infliximab (Table 1). There was no statistical difference noted in the incidence of secondary non-response due to immunogenicity between South Asian and Caucasian American CD patients. Primary non-response, secondary non-response and adverse effects were the leading reasons for discontinuing biological therapy in both UC cohorts (Table 2). South Asian and Caucasian American CD patients experienced similar rates of adverse effects to anti-TNF therapy (Table 3). South Asian UC patients had a higher rate of primary non-response and a lower rate of adverse events with infliximab therapy compared to Caucasian American UC patients (Table 3). CONCLUSION: A cohort of South Asian IBD patients, mainly migrants, showed differing rates of response and adverse effects to biological therapies compared to a Caucasian American cohort. Of note, South Asian CD patients had higher rates of primary response to anti-TNF therapy than Caucasian American CD patients. These results provide insights into ethnic and racial variation in IBD therapeutics.

Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians.

Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DRβ1 plays a key role in the susceptibility to CD (presence of serine being protective, P=3.6×10-67, OR=0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C*12:02, HLA-B*52:01 and HLA-DRB1*1502 (P=1.2×10-28, OR=4.01 [3.14-5.12]).

P53 expression in patients with ulcerative colitis - associated with dysplasia and carcinoma: a systematic meta-analysis

BackgroundTumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC.MethodsPublications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study.ResultsFinal 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P < 0.001), and higher in UC with colorectal cancer (CRC) than in UC with dysplasia (OR = 1.69, P = 0.035). Subgroup analysis of ethnicity (UC group vs. normal tissues) showed that p53 expression was correlated with UC in Asians, but not in Caucasians. When UC with dysplasia was compared to UC group, p53 expression was linked to UC with dysplasia among both Asians and Caucasians. When UC-CRC was compared to UC with dysplasia, p53 expression was not associated with UC-CRC in both Caucasians and Asians.Conclusionsp53 expression was closely associated with UC-CRC development. p53 expression showed different ethnic characteristics among different pathological types of UC.

P274 Assessing the individual risk of acute severe colitis at diagnosis in a South Asian population

Background: A new index has been shown to predict acute severe colitis (ASC) in patients diagnosed with ulcerative colitis (UC) [1]. When applied to patients at the time of diagnosis, this index can predict the 3 year risk of ASC. This 3 point scoring system is the sum of the following indices – 1 point for extensive disease, 1 point for a C-reactive protein [CRP] >10 mg/l, and 1 point for a haemoglobin [Hb] <12 g/dl F or <14 g/dl M. A score of 3/3 gives a 70% predicted risk of developing ACS within 3 years. This index was developed in an Oxford UC cohort, and externally validated in cohorts in Cambridge (UK) and Uppsala (Sweden). It is not clear whether this index would apply accurately to a South Asian (SA) cohort who have a higher rate of extensive disease at diagnosis, but a less aggressive disease course [2] We aim to assess whether this index can be applied to a South Asian population. Methods: South Asian UC patients diagnosed between January 2006 and December 2013 were identified from the hospital's IBD research database. Patients were included if the extent of disease, CRP and Hb data were accessible at the time of diagnosis. Electronic notes were accessed to provide follow up data regarding admissions and treatment in the 3 years following diagnosis. Patients lost to follow up were excluded. Results: 48 UC SA patients were identified over the study period who had the requisite clinical data available to enable a predictive score to be calculated. 6/48 of these patients developed ASC within 3 years of diagnosis. In all index score categories, South Asians patients had a lower percentage of ASC compared to the Oxford median predictive risk. Table 1. South Asian cohort stratified by index score and number with ASC – Side to side comparison with Oxford Development cohort Conclusions: This study suggests that this index over estimated the risk of developing ASC in a South Asian population, which would affect the utility of this index in SA patients where more extensive but less aggressive disease has been demonstrated. Larger studies are needed to confirm these findings.

Familial aggregation of inflammatory bowel disease in patients with ulcerative colitis.

Background/AimsFamilial occurrence of inflammatory bowel disease (IBD) is well documented. Reports from Western countries have shown a higher familial occurrence of ulcerative colitis (UC) in first- and second-degree relatives than that in the Asian UC population. No data are currently available from the Indian subcontinent in this regard. We present our data on the familial aggregation of UC.MethodsRecords of patients with UC followed at the Inflammatory Bowel Disease Clinic at the All India Institute of Medical Sciences, New Delhi from August 2004 to January 2016 were reviewed. Details regarding the prevalence of family history and characteristics of these patients were recorded. Affected family members were contacted and disease characteristics were noted for assessment of familial aggregation.ResultsOf the 2,058 UC patients included in the analysis, a positive family history of IBD was confirmed in 31 patients (1.5%), 24 (77.4%) of whom had only first-degree relatives affected. All the affected relatives had UC and none had Crohn's disease. Among first-degree relatives, siblings were found to have the highest prevalence of IBD (53.3%), followed by parents (26.7%).ConclusionsThe probability of occurrence of IBD in family members of affected North Indian UC patients is lower than that reported in Western populations.

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

CTLA-4 polymorphisms and susceptibility to inflammatory bowel disease: A meta-analysis

ObjectiveThe aim of this study was to explore whether the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) polymorphisms are associated with susceptibility to ulcerative colitis (UC) and Crohn’s disease (CD). MethodsThe authors conducted a meta-analysis on associations between CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms, and (AT)n repeat in the 3′ untranslated region (UTR) and UC and CD susceptibility. ResultsA total of 15 comparison studies were considered in our meta-analysis. Meta-analysis revealed no association between UC and the CTLA-4 +49 G and CTLA-4 −318 T alleles in all subjects (OR=0.982, 95% CI=0.851–1.1339, p=0.804; OR=0.500, 95% CI=0.223–1.124, p=0.094). No association was found between UC and the CTLA-4 CT60 A/G polymorphism in Europeans. However, a significant association was observed between the longer allele (⩾118bp) of the (AT)n and UC in Asian population (OR=6.073, 95% CI=4.246–8.684, p=1.0×10−9). Meta-analysis of the CTLA-4 +49 A/G, −318 C/T, CT60 A/G polymorphisms showed no association with CD. ConclusionsThis meta-analysis demonstrates that the CTLA-4 (AT)n repeat in 3′ UTR may be associated with susceptibility to UC in Asians, while no association was found between the CTLA-4 +49 A/G, −318 C/T, and CD60 A/G polymorphism and susceptibility to UC and CD.

Racial/Ethnic and Regional Differences in the Prevalence of Inflammatory Bowel Disease in the United States

Background: The magnitude of racial/ethnic and regional differences in the prevalence of inflammatory bowel disease (IBD) in the United States remains largely unknown. Aims: To estimate differences in the prevalence of IBD by race/ethnicity and region. Methods: The Medical Expenditure Panel Survey, a nationally representative survey of US households and medical conditions, was used. A multivariate logistic model was used in statistical analysis. Results: Among 202,468 individuals surveyed during 1996-2007, 316 were diagnosed with IBD (26 Blacks, 21 Hispanics, and 5 Asians). The prevalence of IBD was higher in Whites [Crohn's disease: 154; ulcerative colitis (UC): 89] than Blacks (Crohn's disease: 68; UC: 25), Hispanics (Crohn's disease: 15; UC: 35), and Asians (Crohn's: 45; UC: 40) (all p < 0.05, except for UC in Asians). The differences in Crohn's disease between Whites and minorities and the difference in UC between Whites and Blacks remained significant in multivariate analysis. In multivariate analysis, there was no regional difference in the prevalence of Crohn's disease, but the prevalence of UC was higher in the Northeast than the South (p < 0.05). Conclusions: There were significant racial/ethnic differences in the prevalence of IBD in the USA. The underlying etiology of these differences warrants additional research.

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis

To investigate the association of macrophage migration inhibitory factor (MIF) promoter polymorphisms with inflammatory bowel disease (IBD) risk. One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP -173G > C (rs755622) and the repeat polymorphism CATT₅₋₈ (rs5844572) using a pre-designed TaqMan SNP assay and capillary electrophoresis, respectively. Data were analysed for single site and haplotype association with IBD risk and phenotype. Meta-analysis was employed, to assess cumulative evidence of association of MIF -173G > C with IBD. All published genotype data for MIF -173G > C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies. Imputed genotypes for MIF -173G > C were generated from the Wellcome Trust Case Control Consortium (and National Institute of Diabetes and Digestive and Kidney Diseases). Separate meta-analyses were performed on Caucasian Crohn's disease (CD) (3863 patients, 6031 controls), Caucasian ulcerative colitis (UC) (1260 patients, 1987 controls), and East Asian UC (416 patients and 789 controls) datasets using the Mantel-Haenszel method. The New Zealand dataset had 93% power, and the meta-analyses had 100% power to detect an effect size of OR = 1.40 at α = 0.05, respectively. In our New Zealand dataset, single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD, UC, and IBD or disease phenotype (all P values > 0.05). Haplotype analysis found the CATT₅/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients (0.6 vs 0.01; P = 0.03, OR = 0.22; 95%CI: 0.05-0.99), but this association did not survive bonferroni correction. Meta-analysis of our New Zealand MIF -173G > C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD, UC, or overall IBD. Similarly, meta-analysis of all published MIF -173G > C data from East Asian datasets (416 UC patients, 789 controls) found no association of this promoter polymorphism with UC. We found no evidence of association of MIF promoter polymorphisms with IBD.

Association between CD14 Gene C-260T Polymorphism and Inflammatory Bowel Disease: A Meta-Analysis

BackgroundThe gene encoding CD14 has been proposed as an IBD-susceptibility gene with its polymorphism C-260T being widely evaluated, yet with conflicting results. The aim of this study was to investigate the association between this polymorphism and IBD by conducting a meta-analysis.Methodology/Principal FindingsSeventeen articles met the inclusion criteria, which included a total of 18 case-control studies, including 1900 ulcerative colitis (UC) cases, 2535 Crohn's disease (CD) cases, and 4004 controls. Data were analyzed using STATA software. Overall, association between C-260T polymorphism and increased UC risk was significant in allelic comparison (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.02–1.43; P = 0.027), homozygote model (OR = 1.44, 95% CI: 1.03–2.01; P = 0.033), as well as dominant model (OR = 1.36, 95% CI: 1.06–1.75; P = 0.016). However, there was negative association between this polymorphism and CD risk across all genetic models. Subgroup analyses by ethnicity suggested the risk-conferring profiles of -260T allele and -260 TT genotype with UC in Asians, but not in Caucasians. There was a low probability of publication bias.Conclusions/SignificanceExpanding previous results of individual studies, our findings demonstrated that CD14 gene C-260T polymorphism might be a promising candidate marker in susceptibility to UC, especially in Asians.

Sa1268 Natural History and Risk Factors for Proctocolectomy in Asian Ulcerative Colitis

Objective: Ulcerative Colitis (UC) is rare in Asia but has seen a rise in prevalence over the past decade. Previous studies have suggested that UC is milder in Asians and fewer Asian patients require proctoproctocolectomy. The aim of the studywas to determine the proportion of Singaporean UC patients who required proctoproctocolectomy and the risk factors associated with the need for surgery in our cohort of patients. Methods: This is a retrospective study of 453 Asian UC patients seen at the Singapore General Hospital (SGH), Changi General Hospital (CGH) and National University of Singapore (NUH) from 1970 to 2011. Data was reviewed from case notes and electronic records. Cox proportional hazards model was used to identify univariate and multivariate risk factors for proctocolectomy. Results: There were 317 (70.0%) Chinese, 69 (15.2%) Indian, 45 (9.9%) Malay, and 22 (4.9%) patients of other Asian ethnicities in the study cohort. Male-to-female ratio was 1.5:1 (268:186). The majority of patients presented between the ages of 30 to 40 years old (28.5%), with no bimodal peak in age presentation. The mean duration from symptom onset to diagnosis was 22.9 months. At diagnosis, 116 (25.6%) patients presented with proctitis, 186 (42.6%) with left sided disease, and 139 (31.8%) with extensive colitis. 63 (13.9%) patients were steroid dependent. Azathioprine was eventually started in 61 (19.2%) Chinese, 19 (27.5%) Indian and 10 (22.2%) Malay patients, while proctocolectomy was required in 33 (10.4%) Chinese, 8 (10.1%) Indian and 4 (8.9%) Malay patients. The most common indications for proctocolectomy was medically refractory ulcerative colitis (64.4%) followed by acute severe colitis (15.6%) and cancer or dysplasia (13.3%). Risk factors associated with proctocolectomy were ESR more than 26 mm/h at diagnosis (p = 0.026), hemogoblin less than 12 g/dl at diagnosis (p = 0.015), steroid dependency (p< 0.0001), hospitalizations due to UC flares (p = 0.028) and extensive colitis (p = 0.037). Multivariate analysis showed that steroid dependency was the only variable independently associated with proctocolectomy (p = 0.001). Cumulative proctocolectomy rates were 3.0% at 1 year, 6.6% at 5 year, 9.2% at 10 year and 23.3% at 30 year. Age at diagnosis, gender, race and time to diagnosis did not affect surgical rates. Conclusion: About 10% of Asian UC patients in Singapore required proctocolectomy. While this is higher than the 3% of Koreans who required surgery for UC, it is lower than what has been reported in Caucasian cohorts. Steroid dependency was the only variable found to be associated with the need for proctocolectomy.

Sa1269 Inflammatory Bowel Disease Therapies Adversely Affect Fertility in Men- a Systematic Review

Objective: Ulcerative Colitis (UC) is rare in Asia but has seen a rise in prevalence over the past decade. Previous studies have suggested that UC is milder in Asians and fewer Asian patients require proctoproctocolectomy. The aim of the studywas to determine the proportion of Singaporean UC patients who required proctoproctocolectomy and the risk factors associated with the need for surgery in our cohort of patients. Methods: This is a retrospective study of 453 Asian UC patients seen at the Singapore General Hospital (SGH), Changi General Hospital (CGH) and National University of Singapore (NUH) from 1970 to 2011. Data was reviewed from case notes and electronic records. Cox proportional hazards model was used to identify univariate and multivariate risk factors for proctocolectomy. Results: There were 317 (70.0%) Chinese, 69 (15.2%) Indian, 45 (9.9%) Malay, and 22 (4.9%) patients of other Asian ethnicities in the study cohort. Male-to-female ratio was 1.5:1 (268:186). The majority of patients presented between the ages of 30 to 40 years old (28.5%), with no bimodal peak in age presentation. The mean duration from symptom onset to diagnosis was 22.9 months. At diagnosis, 116 (25.6%) patients presented with proctitis, 186 (42.6%) with left sided disease, and 139 (31.8%) with extensive colitis. 63 (13.9%) patients were steroid dependent. Azathioprine was eventually started in 61 (19.2%) Chinese, 19 (27.5%) Indian and 10 (22.2%) Malay patients, while proctocolectomy was required in 33 (10.4%) Chinese, 8 (10.1%) Indian and 4 (8.9%) Malay patients. The most common indications for proctocolectomy was medically refractory ulcerative colitis (64.4%) followed by acute severe colitis (15.6%) and cancer or dysplasia (13.3%). Risk factors associated with proctocolectomy were ESR more than 26 mm/h at diagnosis (p = 0.026), hemogoblin less than 12 g/dl at diagnosis (p = 0.015), steroid dependency (p< 0.0001), hospitalizations due to UC flares (p = 0.028) and extensive colitis (p = 0.037). Multivariate analysis showed that steroid dependency was the only variable independently associated with proctocolectomy (p = 0.001). Cumulative proctocolectomy rates were 3.0% at 1 year, 6.6% at 5 year, 9.2% at 10 year and 23.3% at 30 year. Age at diagnosis, gender, race and time to diagnosis did not affect surgical rates. Conclusion: About 10% of Asian UC patients in Singapore required proctocolectomy. While this is higher than the 3% of Koreans who required surgery for UC, it is lower than what has been reported in Caucasian cohorts. Steroid dependency was the only variable found to be associated with the need for proctocolectomy.

Differences in Inflammatory Bowel Disease Phenotype between South Asians and Northern Europeans Living in North West London, UK

The incidence and prevalence of inflammatory bowel disease (IBD) is increasing throughout Asia. Since the 1950s, there has been substantial migration from South Asia (India, Pakistan, and Bangladesh) to the United Kingdom. The aim of this study was to define the clinical phenotype of IBD in UK South Asians living in North West London, and to compare the results with a white Northern European IBD cohort. The phenotypic details of 367 South Asian IBD patients (273 ulcerative colitis (UC) and 94 Crohn's disease (CD)), undergoing active follow-up in five North West London hospitals, were compared with those of 403 consecutively collected white Northern European IBD patients (188 UC and 215 CD). The phenotype of IBD differed significantly between the two populations. 63.0% of South Asian UC patients had extensive colitis compared with 42.5% of the Northern European cohort (P < 0.0001). Proctitis was uncommon in South Asian UC patients (9.9 vs. 26.1% in Northern European patients, P<0.0001). In the South Asian CD cohort, disease location was predominantly colonic (46.8%). CD behavior differed significantly between the groups, with less penetrating disease compared with Northern Europeans (P=0.01) and a reduced need for surgery (P=0.003). The phenotype of IBD in South Asians living in North West London is significantly different from that of a white Northern European IBD cohort. Knowledge of ethnic variations in disease phenotype may help to identify key genetic, environmental, and behavioral factors contributing to the development of IBD.

Relationship between the polymorphism of tumor necrosis factor-α-308 G&gt;A and susceptibility to inflammatory bowel diseases and colorectal cancer: a meta-analysis

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are common health problems worldwide. Tumor necrosis factor (TNF) is a type of cytokine that induces inflammation and inhibits tumorigenesis. Several studies have assessed the relationship between the polymorphism of TNF-α-308 G>A and the susceptibility to IBD and CRC; however, the results have been controversial. In addition, the hypothesis whether the increased risk of CRC in IBD patients could be partly ascribed to the polymorphism of TNF-α-308 G>A was unclear. Therefore, we conducted this meta-analysis to confirm these associations. Pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated on the basis of data from 14, 18, and 7 studies from a total of 27 studies for the associations between the polymorphism of TNF-α-308 G>A and ulcerative colitis, Crohn's disease (CD) and CRC. In Europeans, the AA genotype increased the risk of ulcerative colitis (UC) (OR, 2.041; 95% CI, 1.261-3.301) and CD (OR, 1.730; 95% CI, 1.168-2.564) significantly, without obvious heterogeneity and publication bias. Meanwhile, the GA genotype increased the risk of UC in Asians (OR, 2.360; 95% CI, 1.269-4.390) significantly. However, no significant association was observed for CRC in any ethnic population. The results of this meta-analysis suggested that the polymorphism of TNF-α-308 G>A participates in modifying the susceptibility to UC and CD in Europeans and Asians. The increased risk of CRC in IBD patients should be clarified as the combined effects of polymorphisms in TNF-α and other cytokines, and the interaction with environmental factors, in future studies.