Indicators of suboptimal response to anti-tumor necrosis factor therapy in patients from China with inflammatory bowel disease: results from the EXPLORE study.

BACKGROUND: Prevalence of inflammatory bowel disease (IBD) is increasing in China. The EXPLORE study evaluated the incidence and indicators of suboptimal responses to first-line anti-tumor necrosis factor (TNF) in patients with ulcerative colitis (UC) or Crohn's disease (CD). We present results for the mainland China subgroup. METHODS: A retrospective chart review was performed in adults with IBD at 10 centers in mainland China who initiated anti-TNF therapy between 01 March 2010 and 01 March 2015. The cumulative incidence of suboptimal response to first-line anti-TNF therapy was assessed over 24 months using the Kaplan-Meier method. Indicators of suboptimal response were: dose escalation, discontinuation, augmentation with non-biologic therapy, or IBD-related surgery/hospitalization. At site initiation, a survey was conducted with participating physicians to identify barriers to anti-TNF use. RESULTS: Of 287 patients (72% male) examined, 16/35 (45.7%) with UC and 123/252 (48.8%) with CD experienced a suboptimal response to first-line anti-TNF therapy at any point during the observation period (median 27.6 and 40.0 months, respectively). At 1 and 2 years post anti-TNF initiation, the cumulative incidence of suboptimal response was 51.4% and 75.7% for UC and 45.4% and 57.0% for CD, respectively. Median time to first suboptimal response was 7.2 months for UC and 14.3 months for CD. The most frequent indicator of suboptimal response was discontinuation of anti-TNF therapy (9/16, 56.3%) for UC and IBD-related hospitalization for CD (69/123, 56.1%) followed by augmentation with non-biologic therapy for both cohorts (5/16, 31.3% for UC and 28/123, 22.8% for CD). Dose escalation was the least frequent indicator of suboptimal response to anti-TNF therapy (CD: 4/123, 3.3%; UC: not cited as an indicator). The cumulative incidence of suboptimal response within 4 months of first-line anti-TNF therapy (primary non-response) was over 30% in both cohorts. Financial reasons and reimbursement were identified by surveyed physicians as the most common barriers to prescribing an anti-TNF therapy. CONCLUSIONS: Over one-half of patients with IBD are at risk of experiencing a suboptimal response to first-line anti-TNF therapy at 2 years post-initiation in China. This study highlights a substantial unmet need associated with anti-TNF therapies in China. (Clinicaltrials.gov identifier: NCT03090139).

Ustekinumab trough concentration affects clinical and endoscopic outcomes in patients with refractory Crohn's disease: a Chinese real-world study.

BACKGROUND: Ustekinumab (UST), a newly-used biologic targeting p40 subunit of IL12 and IL23 in China, exerts a confirmed therapeutic effect on the induction and maintenance therapies for refractory Crohn's disease (CD). Therapeutic drug monitoring based on trough and antibody concentration is of core importance when treating patients who lose response to UST. We aimed to analyze the UST exposure-response relationship in CD treatment in the real-world setting. METHODS: We retrospectively enrolled patients with CD who received UST between March 1, 2020 and May 31, 2021, at the inflammatory bowel disease (IBD) center of the Sun Yat-Sun Affiliated Sixth Hospital. Baseline characteristic information, biomarker examination, clinical outcomes determined by the Crohn's disease activity index (CDAI), and endoscopic outcomes evaluated using a simple endoscopic score for Crohn's disease (SES-CD) at week 16/20 were collected. The optimal UST cut-off trough concentration was identified using receiver operating characteristic curve (ROC) analysis. RESULTS: Nineteen eligible patients were included in the study, the mean age was 29.1 ± 9.1 years and the mean disease duration was 5.5 ± 4.7 years. At the initiation of the study, 89.5% of the patients had been exposed to prior biologics, 42.1% had previous CD-related surgeries, and 52.6% had perianal diseases. At week 16/20 after the UST initiation, clinical response, clinical remission, endoscopic response, and endoscopic remission were 89.5%, 84.2%, 42.2%, and 73.7%, respectively. The cut-off optimal trough concentration for UST was 1.12 µg/mL, as determined by the ROC with an area under the curve (AUC) of 0.78, sensitivity of 87.5%, and specificity of 72.7%. Patients with a UST trough concentration > 1.12 µg/mL had a significantly higher rate of endoscopic remission than those without (70.0% vs. 11.1%, P = 0.02). CONCLUSIONS: UST is an effective therapeutic option for refractory CD treatment. A UST trough concentration above 1.12 µg/mL was associated with endoscopic remission at week 16/20 after UST initiation. Trial registration This study was approved and retrospectively registered by the Ethics Committee of Sun Yat-Sen University (2021ZSLYEC-066, March 29, 2021) and the Clinical Trial Registry (NCT04923100, June 10, 2021).

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia.

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Early serum infliximab trough level and mucosal healing could be predictors for one-year outcome after initiating therapy in Crohn's disease.

BACKGROUND AND AIMS: Serum infliximab trough level(S-IFX) and antibody were documented to correlate with clinical response. The aim of this study was to identify the relationship between early S-IFX, early mucosal healing (MH) and one-year outcome in a cohort on maintenance IFX therapy in Crohn's disease (CD). METHODS: The study group comprised of retrospectively enrolled patients diagnosed for Crohn's disease (n = 108). Patients received scheduled maintenance therapy after response to IFX induction, and had undergone the early S-IFX test and endoscopic examination at week 14. Clinical outcomes were evaluated during maintenance therapy until week 52. RESULTS: Early S-IFX was 4.78 ± 6.16 ug/ml in all the patients and 19% (21/108) of them developed antibodies, and 52 patients reached early MH. During 52 weeks' follow-up. Twenty-eight percent (30/108) of patients showed loss of response to IFX. Patients who lost response had lower early S-IFX than those who had sustained response (3.01 ± 3.66 vs. 5.47 ± 6.79 ug/ml, p = .02; 48 vs. 23%, p = .02). At week 52, 73 patients had repeated endoscopy and 42% of them reached MH. Early S-IFX had a predictive value on MH at week 52. When early S-IFX > 2.5 ug/ml, the sensitivity for predicting MH at week 52 was 87%, and the specificity were 61% (AUC = 0.73, p < .01). The combined predictive value of early S-IFX and early MH became stronger. Only 6% (1/18) of those patients who had low early S-IFX and had not reached early MH could reach MH at week 52. CONCLUSIONS: Early S-IFX and early MH could predict one-year response after initiating IFX therapy in Crohn's disease.

Population Density and Risk of Inflammatory Bowel Disease: A Prospective Population-Based Study in 13 Countries or Regions in Asia-Pacific.

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

Polymorphisms of the TNF Gene and Three Susceptibility Loci Are Associated with Crohn's Disease and Perianal Fistula Crohn's Disease: A Study among the Han Population from South China.

BACKGROUND Although 90 susceptibility loci of Crohn's disease (CD) have been confirmed in the Asian population, susceptibility genes for perianal fistula of CD (pCD) in this population remain unknown. This study explored susceptibility genes for CD and pCD in the Han population from South China. MATERIAL AND METHODS In total, 490 patients diagnosed with CD between July 2012 and June 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were included and divided into the CD group (n=240) and the pCD group (n=250). The healthy control group was composed of 260 volunteers. Peripheral blood samples were taken, and single nucleotide polymorphism (SNP) locus sequencing was used to screen for susceptibility loci. SNPs were sequenced using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. RESULTS Nine SNPs in TNFSF1 on chromosome 9 were associated with CD. Among them, the rs6478106 locus is a risk locus for CD. The distribution frequency of the T allele of the rs6478106 SNP was significantly different between cases and controls (32.49% versus 18.27%, P<0.001). Rs72553867, located in the IRGM gene on chromosome 5, rs4409764, located in the NKX2-3 gene on chromosome 10, and rs3731772, located in the AOX1 gene on chromosome 2, were susceptibility factors for pCD. Nine SNPs located in TNFSF15 on chromosome 9 were related to CD in Han individuals from Southern China. CONCLUSIONS The rs6478106 T allele is associated with the risk of CD in the investigated population. SNPs rs72553867 (IRGM gene), rs4409764 (NKX2-3 gene), and rs3731772 (AOX1 gene) increase the risk of pCD.

Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: Risk assessment.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti-TNF therapy and (ii) screening for TB infection prior to commencing anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 2: Management.

Because anti-tumor necrosis factor (anti-TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti-TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment. Twenty-three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web-based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti-TNF therapy, (4) monitoring during anti-TNF therapy, and (5) management of an active TB infection after anti-TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti-TNF treatment.

Smoking and Inflammatory Bowel Disease: A Comparison of China, India, and the USA.

BACKGROUND: Cigarette smoking is thought to increase the risk of Crohn's disease (CD) and exacerbate the disease course, with opposite roles in ulcerative colitis (UC). However, these findings are from Western populations, and the association between smoking and inflammatory bowel disease (IBD) has not been well studied in Asia. AIMS: We aimed to compare the prevalence of smoking at diagnosis between IBD cases and controls recruited in China, India, and the USA, and to investigate the impact of smoking on disease outcomes. METHODS: We recruited IBD cases and controls between 2014 and 2018. All participants completed a questionnaire about demographic characteristics, environmental risk factors and IBD history. RESULTS: We recruited 337 participants from China, 194 from India, and 645 from the USA. In China, CD cases were less likely than controls to be current smokers (adjusted odds ratio [95% CI] 0.4 [0.2-0.9]). There was no association between current or former smoking and CD in the USA. In China and the USA, UC cases were more likely to be former smokers than controls (China 14.6 [3.3-64.8]; USA 1.8 [1.0-3.3]). In India, both CD and UC had similar current smoking status to controls at diagnosis. Current smoking at diagnosis was significantly associated with greater use of immunosuppressants (4.4 [1.1-18.1]) in CD cases in China. CONCLUSIONS: We found heterogeneity in the associations of smoking and IBD risk and outcomes between China, India, and the USA. Further study with more adequate sample size and more uniform definition of smoking status is warranted.

A validated LC-MS/MS method for the simultaneous determination of thalidomide and its two metabolites in human plasma: Application to a pharmacokinetic assay.

An accurate and sensitive LC-MS/MS method for determining thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in human plasma was developed and validated using umbelliferone as an internal standard. The analytes were extracted from plasma (100 µL) by liquid-liquid extraction with ethyl acetate and then separated on a BETASIL C18 column (4.6 × 150 mm, 5 µm) with mobile phase composed of methanol-water containing 0.1% formic acid (70:30, v/v) in isocratic mode at a flow rate of 0.5 mL/min. The detection was performed using an API triple quadrupole mass spectrometer in atmospheric pressure chemical ionization mode. The precursor-to-product ion transitions m/z 259.1 → 186.1 for thalidomide, m/z 273.2 → 161.3 for 5-hydroxy thalidomide, m/z 273.2 → 146.1 for 5'-hydroxy thalidomide and m/z 163.1 → 107.1 for umbelliferone (internal standard, IS) were used for quantification. The calibration curves were obtained in the concentrations of 10.0-2000.0 ng/mL for thalidomide, 0.2-50.0 ng/mL for 5-hydroxy thalidomide and 1.0-200.0 ng/mL for 5'-hydroxy thalidomide. The method was validated with respect to linear, within- and between-batch precision and accuracy, extraction recovery, matrix effect and stability. Then it was successfully applied to estimate the concentration of thalidomide, 5-hydroxy thalidomide and 5'-hydroxy thalidomide in plasma samples collected from Crohn's disease patients after a single oral administration of thalidomide 100 mg.

Early Course of Inflammatory Bowel Disease in a Population-Based Inception Cohort Study From 8 Countries in Asia and Australia.

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Asia, but little is known about disease progression in this region. The Asia-Pacific Crohn's and Colitis Epidemiology Study was initiated in 2011, enrolling subjects from 8 countries in Asia (China, Hong Kong, Indonesia, Sri Lanka, Macau, Malaysia, Singapore, and Thailand) and Australia. We present data from this ongoing study. METHODS: We collected data on 413 patients diagnosed with IBD (222 with ulcerative colitis [UC], 181 with Crohn's disease [CD], 10 with IBD unclassified; median age, 37 y) from 2011 through 2013. We analyzed the disease course and severity and mortality. Risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: The cumulative probability that CD would change from inflammatory to stricturing or penetrating disease was 19.6%. The cumulative probabilities for use of immunosuppressants or anti-tumor necrosis factor agents were 58.9% and 12.0% for patients with CD, and 12.7% and 0.9% for patients with UC, respectively. Perianal CD was associated with an increased risk of anti-tumor necrosis factor therapy within 1 year of its diagnosis (hazard ratio, 2.97; 95% confidence interval, 1.09-8.09). The cumulative probabilities for surgery 1 year after diagnosis were 9.1% for patients with CD and 0.9% for patients with UC. Patients with CD and penetrating disease had a 7-fold increase for risk of surgery, compared with patients with inflammatory disease (hazard ratio, 7.67; 95% confidence interval, 3.93-14.96). The overall mortality for patients with IBD was 0.7%. CONCLUSIONS: In a prospective population-based study, we found that the early course of disease in patients with IBD in Asia was comparable with that of the West. Patients with CD frequently progress to complicated disease and have accelerated use of immunosuppressants. Few patients with early stage UC undergo surgery in Asia. Increasing our understanding of IBD progression in different populations can help optimize therapy and improve outcomes.

Efficacy of exclusive enteral nutrition in complicated Crohn's disease.

AIM: To investigate the efficacy of exclusive enteral nutrition (EEN) in induction of remission in adult active Crohn's disease (CD) complicated with intestinal fistula/abdominal abscess or inflammatory intestinal stricture. METHOD: Patients diagnosed with active CD with complications were recruited between July 2013 and July 2015. Patients were offered EEN for 12 weeks. Patients with abscess received antibiotic treatment with or without percutaneous drainage. Clinical variables were recorded (ClinicalTrials.gov Identifier: NCT02887287). RESULTS: Forty-one patients with CD and with intestinal fistula/abdominal abscess or inflammatory intestinal stricture aged 18-60 years, were included. Ten patients were accompanied with stenosis and 33 with intestinal fistula/abscess. After 12 weeks of EEN, the Crohn's disease activity index significantly decreased (223.43 ± 65.5 vs. 106.77 ± 42.73, p ≤ .001), and 80.5% of patients achieved full clinical remission totally. Fistula closure after EEN was observed in 75% of patients with entero-cutaneous fistula. In patients with stenosis, 20% had no response to EEN and were transferred for surgery. Partial remission and full remission were observed in 20% and 60% of patients after 12 weeks of EEN, respectively. Intra-abdominal abscess resolved in 76% of patients. Seventeen patients who had mucosal ulcers underwent colonoscopy before and after EEN, 47% achieved mucosal healing after the treatment. The inflammatory index of patients significantly decreased (p ≤ .01), nutritional parameters increased (p ≤ .01) and the European Nutritional Risk Screening (2002) decreased (p ≤ .01). CONCLUSION: EEN is effective in inducing early clinical remission, mucosal healing, promoting fistula closure and reducing the size of abscess in adult CD patients with complications.

The Future of IBD Therapy: Where Are We and Where Should We Go Next?

BACKGROUND: The advent of biologic agents opens up a new era for the treatment of inflammatory bowel disease (IBD). In this era, the treatment goal has evolved from the traditional goal of clinical remission to a combination of clinical remission, laboratory normalization and mucosal healing, designated as 'complete deep remission'. Such complete deep remission comprises a more ambitious disease control strategy that is believed to probably modify the natural course of IBD. KEY MESSAGES: To achieve this goal, optimization of current strategy and introduction of novel therapies have gained significant interest. In this concise review, we aim to provide an overview of the current status and future direction of IBD treatment. Specifically, we will describe the application of personalized therapy, development of new biologics, intestinal microbiome manipulation and out-of-the-box agents for IBD. CONCLUSIONS: More evidence is still desirable to better optimize the current treatment and apply novel biologics. Personalized medicine has the potential to optimize efficacy, decrease the risk of adverse events and minimize costs and should be proposed as a standard of care for the management of IBD.

Environmental risk factors in inflammatory bowel disease: a population-based case-control study in Asia-Pacific.

OBJECTIVE: The rising incidence of inflammatory bowel disease in Asia supports the importance of environmental risk factors in disease aetiology. This prospective population-based case-control study in Asia-Pacific examined risk factors prior to patients developing IBD. DESIGN: 442 incident cases (186 Crohn's disease (CD); 256 UC; 374 Asians) diagnosed between 2011 and 2013 from eight countries in Asia and Australia and 940 controls (frequency-matched by sex, age and geographical location; 789 Asians) completed an environmental factor questionnaire at diagnosis. Unconditional logistic regression models were used to estimate adjusted ORs (aOR) and 95% CIs. RESULTS: In multivariate model, being breast fed >12 months (aOR 0.10; 95% CI 0.04 to 0.30), antibiotic use (aOR 0.19; 0.07 to 0.52), having dogs (aOR 0.54; 0.35 to 0.83), daily tea consumption (aOR 0.62; 0.43 to 0.91) and daily physical activity (aOR 0.58; 0.35 to 0.96) decreased the odds for CD in Asians. In UC, being breast fed >12 months (aOR 0.16; 0.08 to 0.31), antibiotic use (aOR 0.48; 0.27 to 0.87), daily tea (aOR 0.63; 0.46 to 0.86) or coffee consumption (aOR 0.51; 0.36 to 0.72), presence of hot water tap (aOR 0.65; 0.46 to 0.91) and flush toilet in childhood (aOR 0.71; 0.51 to 0.98) were protective for UC development whereas ex-smoking (aOR 2.02; 1.22 to 3.35) increased the risk of UC. CONCLUSIONS: This first population-based study of IBD risk factors in Asia-Pacific supports the importance of childhood immunological, hygiene and dietary factors in the development of IBD, suggesting that markers of altered intestinal microbiota may modulate risk of IBD later in life.

Computed tomographic enterography adds value to colonoscopy in differentiating Crohn's disease from intestinal tuberculosis: a potential diagnostic algorithm.

BACKGROUND: Crohn's disease and intestinal tuberculosis (ITB) are chronic granulomatous disorders that are difficult to distinguish. Computed tomographic enterography (CTE) yields striking findings for Crohn's disease in the small bowel but its role in differentiating Crohn's from ITB is undefined. This prospective study aimed to investigate the value of CTE for differential diagnosis between Crohn's disease and ITB. PATIENTS AND METHODS: 105 consecutive patients (67 Crohn's, 38 ITB) who underwent CTE and colonoscopy were enrolled. CTE findings and colonoscopic parameters were compared between Crohn's disease and ITB by blinded reviewers. Based on univariate and multiple logistic regression analyses, a diagnostic algorithm combining colonoscopy and CTE was formulated. and its performance validated on 60 new patients (40 Crohn's, 20 ITB). RESULTS: On univariate analysis of CTE findings, proximal small-bowel involvement, asymmetrical mural thickening, segmental small-bowel lesions, mural stratification, the comb sign, and mesentery fibrofatty proliferation were significantly more common in Crohn's disease, whereas mesenteric lymph node change (calcification or central necrosis) and focal ileocecal lesions were more common in ITB. On multivariate analysis, segmental small-bowel involvement (odds ratio [OR] 0.104, 95 % confidence interval [95 %CI] 0.022 - 0.50), and comb sign (OR 0.02, 95 %CI 0.003 - 0.26) were independent predictors of Crohn's. Combining CTE and colonoscopic findings increased the accuracy of diagnosing either Crohn's disease or ITB from 66.7 % (70/105) to 95.2 % (100/105) in the development set (P < 0.001). Sensitivity, specificity, and area under the curve for receiver-operating characteristic (ROC) in the validation dataset were 92.5 %, 80 %, and 0.862 (95 %CI 0.75 - 0.98), respectively. CONCLUSIONS: CTE adds unique information to colonoscopy in differential diagnosis between Crohn's disease and ITB, allowing correct diagnosis in most patients.

The impact of glutathione S-transferase genotype and phenotype on the adverse drug reactions to azathioprine in patients with inflammatory bowel diseases.

Azathioprine (AZA) is a thiopurine prodrug which is widely used in patients with inflammatory bowel disease (IBD). However, the use is limited in one-third of patients because of adverse drug reactions (ADRs) or a lack of clinical response. It has been considered that the polymorphic enzyme thiopurine S-methyltransferase (TPMT) plays an important role in the in vivo process of AZA and the occurrence of its myelotoxicity. Glutathione S-transferase (GST) mutation is another pharmacogenetic polymorphism which is probably involved in AZA metabolism and tolerance. The aim of this study was to investigate the association among GST polymorphism, enzyme activity and AZA-related ADRs in Chinese Han patients with IBD. We found that the patients who became neutropenic had a significantly higher GSTs activity when compared with of the patients who did not develop ADRs (analysis of variance, P < 0.001). There was also a significant underrepresentation of GSTP1*-105V allele among patients developing ADRs (odds ratio [OR] = 0.125, 95% confidence interval [CI] = 0.022-0.709, P = 0.0012). The patients with higher GST activity constituted a pharmacogenetic high risk group for leucopenia during AZA treatment. GST-P1 Ile105/Ile105 genotype appeared to be a promising marker indicating predisposition to AZA-related ADRs.

Increased expression of IL17A in human gastric cancer and its potential roles in gastric carcinogenesis.

Inflammatory cytokines modulate immune responses in the tumor microenvironment during progression. The role of interleukin (IL) 17A in cancer is currently under debate. We aim to investigate the expression of IL17A in situ tumors as well as in nontumor gastric mucosa tissues and further explore the functional significance of IL17A on gastric cancer cells in vitro. We found that compared with nontumor regions, the expression of IL17A were increased significantly in tumors of gastric cancer patients (P=0.007). The immunoreactivity for IL17A was found only in cytoplasm of inflammatory cells as well as vascular endothelial cells but not in tumor cells. Consistently, IL17A transcription was silenced in a variety of gastric cancer cell lines. In vitro, recombinant human IL17A protein promotes cell proliferation and monolayer wound healing of both AGS and SGC7901cells, in a dose-dependent manner. Besides, IL17A inhibits H2O2-induced cell apoptosis. Expression of IL6 and MMP13 mRNA was increased significantly after IL17A stimulation. These data suggest that accumulation of intratumoral IL17A-producing cells may promote gastric cancer progression directly or by inducing key signal transduction pathways implicated in gastric carcinogenesis.

Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in China with urbanization and socioeconomic development. There is however a lack of prospective, population-based epidemiology study on IBD in China. The aim of the study is to define the incidence and clinical characteristics of IBD in a developed region of Guangdong Province in China. METHODS: A prospective, population-based incidence study was conducted from July 2011 to June 2012 in Zhongshan, Guangdong, China. All newly diagnosed IBD cases in Zhongshan were included. RESULTS: In total, 48 new cases of IBD (17 Crohn's disease [CD]; 31 ulcerative colitis [UC]) were identified over a 1-year period from July 2011. Age-standardized incidence rates for IBD, UC, and CD were 3.14, 2.05, and 1.09 per 100,000 persons, respectively. The median age of UC was 38, and that of CD was 25. Terminal ileum involvement only (L1), isolated colonic disease (L2), and ileocolonic disease (L3) were reported in 24%, 6%, and 71% of patients with CD, respectively. Twenty-four percent of patients had coexisting upper gastrointestinal disease (L4). Inflammatory (B1), stricturing (B2), and penetrating (B3) behavior were seen in 65%, 24%, and 12% of CD patients, respectively. Fifty-nine percent of CD and 26% of UC patients had extra-intestinal manifestations. CONCLUSIONS: This is the first prospective, population-based IBD epidemiological study in a developed region of China. The incidence of IBD is similar to that in Japan and Hong Kong but lower than that in South Korea and Western countries.

[The prevalence and characteristics of anemia in Crohn's disease in the Chinese].

OBJECTIVE: To investigate the prevalence and characteristics of anemia among patients with Crohn's disease (CD) in Chinese population and identify the possible risk factors. METHODS: A cross-sectional study was performed in 441 patients with CD enrolled from the First Affiliated Hospital of Sun Yat-Sen University between January 2003 and May 2012. The prevalence, severity, type of anemia in these patients was assessed when diagnosis was confirmed. A multivariate logistic regression including 122 patients was performed to screen risk factors of anemia. RESULT: The prevalence of anemia was 64.4% (284/441) with 69.0% (196/284) mild anemia, 28.9% (82/284) moderate anemia and 2.1% (6/284) severe anemia. The most common morphological classification was hypochromic microcytic anemia (43.7%, 124/284). Multivariate logistic regression showed the predictive factors for anemia were higher levels of modified Crohn's disease activity index (CDAI) (OR = 1.007, 95% CI 1.002-1.013), platelet count (OR = 1.007, 95% CI 1.001-1.012), erythrocyte sedimentation rate (OR = 1.024, 95% CI 1.000-1.048), penetrating behavior (OR = 16.952, 95% CI 2.626-108.626), structuring behavior (OR = 6.717, 95% CI 1.583-28.507), older age at diagnosis (OR = 1.065, 95% CI 1.012-1.121),and lower body mass index (BMI) (OR = 0.769, 95% CI 0.633-0.935). CONCLUSIONS: Anemia is a common complication in patients with CD among Chinese population. Activity of the underlying disease, older age at diagnosis, penetrating or structuring disease behavior and low BMI are the risk factors.

Clinical characteristics and risk factors of ovarian reserve decreases in women with Crohn's disease: a case-control study.

BACKGROUND: Crohn's disease (CD), often occurring in women of child-bearing age, can decline the fertility rate. However, whether it reduces ovarian reserve has been rarely reported. This study aimed to evaluate the ovarian reserve in women with CD from the perspective of anti-Müllerian hormone (AMH), and explore the factors that can decrease ovarian reserve. METHODS: A case-control retrospective study was designed. We analyzed the AMH levels in a total of 135 CD women and 878 healthy controls. Through propensity score matching, the subjects were assigned in a ratio of 1:3 to CD group (n = 121) and control group (n = 324). Both groups shared similar basic characteristics, like age, body mass index and smoking status. Serum AMH levels were measured by chemiluminescence. RESULTS: The AMH level in the CD group was significantly lower than that in the control group (2.17 ± 2.23 µg/L vs 3.95 ± 2.01 µg/L, 95%CI [1.34-2.21], P < 0.001). In both groups, the AMH levels decreased as age increased, but without between-group difference in the decreasing rate (P = 0.639). Multivariate analysis showed that age > 30 years (OR, 2.905; 95%CI [1.053-8.531], P = 0.017), disease activity (OR,4.314; 95%CI [1.561-12.910], P = 0.002) and thalidomide use (OR,12.628; 95%CI [4.351 -42.820], P < 0.001) were independent risk factors associated with decreased ovarian reserve (AMH<1.1µg/L). CONCLUSION: Ovarian reserve is lower in CD women than in healthy women. Age, CD activity and medication of thalidomide are risk factors that can aggravate the decline of ovarian reserve.