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Background/Aims: Incidences of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), have been increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend of IBD in Taiwan from 2001 to 2015. Methods: A retrospective study was conducted to analyze data recorded from January 2001 through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry of Health and Welfare, Taiwan. Results: A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 in Taiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereas that of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in 2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-female ratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that of those registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identified among 20 to 39-year-old compared with other age groups. Conclusions: Using Taiwan’s nationwide insurance database, we de termined that the number of patients with CD increased more rapidly during the study period than the number of patients with UC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio. (Intest Res 2019;17:54-62)

Background Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. Methods This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan’s National Health Insurance. Results Between 2001 and 2015, a total of 3806 IBD patients [Crohn’s disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02–4.55) and 1.44 (95% CI 1.26–1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011–2015 and 2001–2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. Conclusion For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

Background The integrity of the gut barrier in patients with inflammatory bowel disease is known to be impaired but the exact mechanisms remain mostly unknown. SHANK3 mutations are associated with autism, and patients with autism are known to have higher proportions of inflammatory bowel disease. Here, we explore the role of SHANK3 in inflammatory bowel disease, both in vivo and in vitro. Methods Dextran sulfate sodium colitis was induced in SHANK3 knockout mice. Transepithelial electrical resistance, paracellular permeability, and Salmonella invasion assays were used to evaluate epithelial barrier function, in vitro and in vivo. Expression of tight junction proteins, protein kinases, and MAP kinase phosphorylation changes were analyzed by immunoblotting after overexpression or knockdown of SHANK3 expression. SHANK3 expression in intestinal tissue from patients with Crohn's disease was analyzed by quantitative polymerase chain reaction and immunohistochemistry. Results SHANK3 knockout mice were more susceptible to dextran sulfate sodium. SHANK3 knockout resulted in a leaky epithelial barrier phenotype, as demonstrated by decreased transepithelial electrical resistance, increased paracellular permeability, and increased Salmonella invasion. Overexpression of SHANK3 enhanced ZO-1 expression, and knockdown of SHANK3 resulted in decreased expression of ZO-1. Regulation of ZO-1 expression by SHANK3 seems to be mediated through a PKCe-dependent pathway. SHANK3 expression correlated with ZO-1 and PKCe in colonic tissue of patients with Crohn's disease. Conclusions The expression level of SHANK3 affects ZO-1 expression and the barrier function in intestinal epithelial cells. This may provide novel insights in Crohn's disease pathogenesis and treatment.

To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients.Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn's disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring.A total of 88 IBD patients [36 patients with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 μg/g as the cut-off. When using 191 μg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS3) with 88% sensitivity and 75% specificity (AUC: 0.87).fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.

Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA).This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone.Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.

Background The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan. Methods A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from January 1998 through December 2008. Results A total of 1591 IBD patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008. Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The standardized mortality ratio (95% CI) was 4.97 (3.72–6.63) for CD and 1.78 (1.46–2.17) for UC, from 1998 to 2008 in Taiwan. Conclusions Using the Taiwan nationwide database for IBD, the incidence and prevalence of IBD in Taiwan significantly increased from 1998 to 2008. The mortality rate was higher for CD patients than UC patients, and both were higher than the general population.

Background & aimsTo date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.MethodsSNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay.ResultsSLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1.ConclusionsSLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.

Background Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. Methods A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients’ demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. Results A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn’s disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p