Fecal calprotectin and lactoferrin as predictors of relapse in patients with quiescent ulcerative colitis during maintenance therapy

Purpose

This prospective study was to evaluate the significance of fecal calprotectin and lactoferrin for the prediction of ulcerative colitis (UC) relapse.

Methods

Eighty UC patients in remission for ≥3 months on mesalamine as maintenance therapy were included. At entry, stool samples were collected for the measurement of calprotectin and lactoferrin. All patients were followed up for the following 12 months. To identify predictive factors for relapse, time-dependent analyses using the Kaplan-Meier graphs and Cox's proportional hazard model were applied.

Results

During the 12 months, 21 patients relapsed. Mean calprotectin and lactoferrin levels were significantly higher in patients with relapse than those in remission (calprotectin—173.7 vs 135.5 μg/g, P?=?0.02; lactoferrin—165.1 vs 130.7 μg/g, P?=?0.03). A cutoff value of 170 μg/g for calprotectin had a sensitivity of 76 % and a specificity of 76 % to predict relapse, while a cutoff value of 140 μg/g for lactoferrin had a sensitivity of 67 % and a specificity of 68 %. In a multivariate analysis, calprotectin (≥170 μg/g) was a predictor of relapse (hazard ratio, 7.23; P?=?0.002). None of the following parameters were significantly associated with relapse: age, gender, duration of UC, number of UC episode, severity of the previous episode, extent of UC, extraintestinal manifestation, and lactoferrin level.

Conclusions

Fecal calprotectin showed a higher sensitivity and specificity than fecal lactoferrin for predicting UC relapse. Fecal calprotectin level appeared to be a significant predictor of relapse in patients with quiescent UC on mesalamine as maintenance therapy.     

Confirmation of three inflammatory bowel disease susceptibility loci in a Chinese cohort

Purpose

Recent genome-wide association studies have identified a number of inflammatory bowel diseases (IBD) susceptibility loci in White populations. The aim of our study was to evaluate whether these susceptibility loci also existed in a Chinese Han IBD population.

Methods

Peripheral blood DNA samples from groups of patients with Crohn’s disease (CD) (n?=?48), ulcerative colitis (UC) (n?=?49), and healthy controls (n?=?50) were genotyped for eight genes. Then, an extended analysis of the relationship between genotype and phenotype was performed.

Results

NOD2-P268S (P?=?0.025) was found to contribute susceptibility to CD in the Chinese population. IL23R-rs11805303 was detected to confer a strong protective effect against UC (P?=?0.010), whereas PTPN2-rs2542151 was significantly associated with an increased risk of UC (P?=?0.001). Further phenotype–genotype analysis revealed that P268S was associated with early age of onset (P?=?0.028), ileal disease (P?=?0.003), and enteric cavity narrowing (P?=?0.007).

Conclusions

The study indicates that IL23R-rs11805303 and PTPN2-rs2542151 might contribute to the development of UC and NOD2-P268S might be involved in the etiology of CD in the Chinese Han population.     

The Prevalence of Clostridium difficile Infection in Pediatric and Adult Patients with Inflammatory Bowel Disease

Objectives

Adults with inflammatory bowel disease (IBD) have a high prevalence of Clostridium difficile infection (CDI). CDI in children with IBD may differ from adults. We aim to compare the prevalence of CDI in hospitalized pediatric and adult IBD patients and patients without IBD.

Methods

The rates of CDI per 1,000 IBD and non-IBD hospitalizations between 1993 and 2012 were examined using the Maryland Health Services Cost Review Commission database. Age, sex and calendar year adjusted incidence rate ratios comparing CDI in pediatrics and adults by type of IBD and with patients without IBD were calculated. p values for trend identifying changes in rates over time were calculated.

Results

Among children, the rate of CDI was over 12 times greater in IBD than non-IBD hospitalizations (p < 0.0001) and among adults, the rate of CDI was four times greater in IBD than non-IBD hospitalizations (p < 0.0001). In adults, CDI was significantly higher in ulcerative colitis (UC) than Crohn’s disease (60.4 per 1,000 vs. 19.8 per 1,000, p < 0.0001) but in children there was no difference in CDI in UC compared with Crohn’s disease (32 per 1,000 vs. 27 per 1,000, p = 0.45). The prevalence of CDI increased in pediatric and adult IBD patients, and patients without IBD, between 1993 and 2012 (p for trend <0.0001).

Conclusions

CDI was more common in adult patients with UC, and no difference was found between CDI and IBD type in pediatrics. There may be different risk factors for CDI during hospitalization between adults and children with IBD.     

Fecal Calprotectin in Pediatric Inflammatory Bowel Disease: A Systematic Review

Background

Inflammatory bowel disease frequently begins during childhood or adolescence. Current tests and procedures for diagnosing and monitoring inflammatory bowel disease are invasive, uncomfortable and costly. Fecal calprotectin is an inflammatory marker tested in several studies including pediatric patients with inflammatory bowel disease.

Methods

A search for articles published up to October 2011 was conducted using MEDLINE and EMBASE databases. We included original English-written articles referred to pediatric patients with inflammatory bowel disease and measured fecal calprotectin levels. We extracted data concerning fecal calprotectin levels in patients with inflammatory bowel disease and in the controls groups, sensitivity, specificity, positive and negative likelihood ratio.

Results

Thirty-four studies were included. Fecal calprotectin levels of patients with inflammatory bowel disease are much higher than those of healthy controls or patients with functional disorders or other gastrointestinal diseases. The results vary greatly when taking all studies into consideration. Nevertheless, in cases of newly diagnosed and/or active inflammatory bowel disease, the results are more homogeneous, with high sensitivity and positive likelihood ratio, low negative likelihood ratio, but moderate specificity. Moreover, 50 μg/g seems to be the most proper cut-off point for the fecal calprotectin test.

Conclusions

The fecal calprotectin test could be used for supporting diagnosis or confirming relapse of inflammatory bowel disease in pediatric patients. A positive result could confirm the suspicion of either inflammatory bowel disease diagnosis or inflammatory bowel disease relapse, due to the high sensitivity of the test, but a negative result should not exclude these conditions, due to its moderate specificity.     

Infliximab in pediatric inflammatory bowel disease rapidly decreases fecal calprotectin levels

AIM: To study the response to infliximab in pediatric inflammatory bowel disease (IBD), as reflected in fecal calprotectin levels. METHODS: Thirty-six pediatric patients with IBD [23 Crohn’s disease (CD), 13 ulcerative colitis (UC); median age 14 years] were treated with infliximab. Fecal calprotectin was measured at baseline, and 2 and 6 wk after therapy, and compared to blood inflammatory markers. Maintenance medication was unaltered until the third infusion but glucocorticoids were tapered off if the pat...     

Fecal calprotectin and serum albumin as markers of gastrointestinal graft versus host disease

Background

Acute graft versus host disease (aGVHD) affects approximately 30–60% of patients after allogeneic hematopoietic stem cell transplantation (HCT) and our ability to predict who develops this complication and their response to treatment is limited. Fecal calprotectin has recently gained popularity as an effective marker of GI inflammation in patients with Inflammatory Bowel Disease (IBD).

PTGER4 modulating variants in Crohn’s disease

Purpose

Variants modulating expression of the prostaglandin receptor 4 (PTGER4) have been reported to be associated with Cohn’s disease (CD), but the clinical impact remains to be elucidated. We analyzed these variants in a large German inflammatory bowel disease (IBD) cohort and searched for a potential phenotype association.

Methods

The variants rs4495224 and rs7720838 were studied in adult German IBD patients (CD, n?=?475; ulcerative colitis (UC), n?=?293) and healthy controls (HC, n?=?467). Data were correlated to results from NOD2 genotyping and to clinical characteristics.

Results

We found a significant association for the rs7720838 variant with overrepresentation of the T allele to CD (p?=?0.0058; OR 0.7703, 95 % CI 0.641–0.926) but not to UC. Furthermore, logistic regression analysis revealed that the presence of the T allele was associated with stricturing disease behavior in CD patients (p?=?0.03; OR 1.84, 95 % CI 1.07–3.16). Interestingly, the chance for developing stricturing disease behavior was enhanced if mutant alleles in both rs7720838 and NOD2 were present (OR 2.87, 95 % CI 1.42–5.81; p?=?0.003). No overall association to CD or UC was found for the rs4495224 variant.

Conclusions

The PTGER4 modulating variant rs7720838 increases susceptibility for CD and might resemble a risk factor for stricturing disease behavior.     

High Serum Vaspin Concentrations in Patients with Ulcerative Colitis

Background

Adipocytokines are associated with energy homeostasis and mediate various immune responses and inflammatory processes. Vaspin is a novel adipocytokine that is thought to exhibit anti-inflammatory effects.

Aim

We aimed to evaluate serum vaspin levels in inflammatory bowel disease (IBD) and determine its possible associations with the course and to clarify its intestinal localization.

Methods

Serum samples were obtained from patients with Crohn’s disease (CD; n = 30) and ulcerative colitis (UC; n = 33) and from healthy volunteers (controls; n = 26). Enzyme-linked immunosorbent assays were performed for all patients. Vaspin immunohistochemical staining was performed for intestines affected with IBD.

Results

Serum vaspin concentrations were significantly higher in patients with UC than in patients with CD and controls (422.9 ± 361.9 vs. 163.4 ± 116.2 vs. 147.5 ± 89.4 pg/mL, respectively; P < 0.01). There was no difference in the serum vaspin concentrations between the patients with CD and controls. There was also no difference in the serum vaspin concentrations between the patients with active IBD and those with inactive IBD. However, the serum vaspin concentrations of most patients with UC increased after remission induction. Vaspin was expressed in the adipocytes of the mesenteric adipose tissues but not in the epithelial or inflammatory cells of large intestines of the patients with IBD.

Conclusions

Serum vaspin concentrations are elevated in patients with UC and increase further after remission induction, suggesting that vaspin may aid the auxiliary diagnosis of UC and may be useful for assessing disease activity in patients.     

Surveillance colonoscopy in patients with inflammatory bowel disease: comparison of random biopsy vs. targeted biopsy protocols

Background

Endoscopic surveillance in patients with long-standing inflammatory bowel disease (IBD) improves early detection of intraepithelial neoplasia (IEN). We aimed to compare three different endoscopic surveillance strategies in the detection of IEN.

Methods

One hundred fifty surveillance colonoscopies (ulcerative colitis, UC n?=?141; Crohn's disease, CD n?=?9) were carried out. Random quadrant biopsies were taken (group I, n?=?50). Chromoendoscopy with indigo carmine was performed and subsequently quadrant biopsies were collected (group II, n?=?50). Patients in group III (n?=?50) underwent confocal endomicroscopy (CEM), and CEM-guided as well as random quadrant biopsies were taken (group III, n?=?50). The findings of CEM were correlated to conventional histology. Patients with high-grade IEN underwent surgery or strict follow-up by patients' request.

Results

In group I (1531 biopsies), no IEN was detected by histology. In group II (1,811 biopsies), chromoendoscopy-guided biopsies revealed high-grade IEN in two patients (4% detection rate). In four patients of group III (1477 biopsies), areas with high-grade IEN were clearly visible by CEM and confirmed by histology (8% detection rate, p?Conclusion Targeted biopsy protocols guided by either chromoendoscopy or CEM led to higher detection rates of IEN and are thus mandatory for surveillance colonoscopies in patients with long-standing UC. Random biopsy protocols should be replaced by chromoendoscopy-guided protocols.     

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

AIM: To investigate matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in pouch mucosa of pediatric onset ulcerative colitis (UC).METHODS: In this cross-sectional study, 28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years (median) after proctocolectomy. Expression of MMPs-3, -7, -8, -9, -12 and -26 and TIMPs-1, -2 and -3 in samples was examined using immunohistochemichal methods, and another biopsy was used to evaluate the grade of histological inflammation. Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion, using a scale marking staining intensity as follows: 0 = less than 20 positive cells; 1 = 20-50 positive cells; 2 = 50-200 positive cells; 3 = over 20 positive cells. Fecal calprotectin and blood inflammatory markers [serum C-reactive protein (CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS: Of the 28 patients with pediatric onset UC, nine had not experienced pouchitis, whereas thirteen reported a single episode, and six had recurrent pouchitis (≥ 4 episodes). At the time of the study, six patients required metronidazole. In all of the others, the most recent episode of pouchitis had occurred over one month earlier, and none were on antibiotics. Only four samples depicted no sign of inflammation, and these were all from patients who had not had pouchitis. Two samples were too small to determine the grade of inflammation, but both had suffered pouchitis, the other recurrent. No sample depicted signs of colonic metaplasia. Most pouch samples showed expression of epithelial (e) and stromal (s) MMP-3 (e, n = 22; s, n = 20), MMP-7 (e, n = 28; s, n = 27), MMP-12 (e, n = 20; s, n =24), TIMP-2 (e, n = 23; s, n = 23) and MMP-3 (e, n = 23; s, n = 28) but MMP-8 (e, n = 0; s, n = 1), MMP-9 (e, n = 0; s, n = 9) and MMP-26 (e, n = 0; s, n = 3) and TIMP-1 (n = 0, both) were lacking. In samples with low grade of inflammatory activity, the epithelial MMP-3 and MMP-7 expression was increased (r = -0.614 and r = -0.472, respectively, P < 0.05 in both). MMPs and TIMPs did not correlate with the markers of inflammation, fecal calprotectin, erythrocyte sedimentation rate, or CRP, with the exception of patients with low fecal calprotectin (< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMP- or TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes. Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP- or TIMP-expression.CONCLUSION: The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease, but inflammation cannot be classified as a reactivation of the disease.     

Psychiatric comorbidities in patients with inflammatory bowel disease

Background

Psychiatric comorbidities are associated with inflammatory bowel disease (IBD). We conducted an observational study to evaluate the prevalence of depression and anxiety in patients with IBD.

Methods

Seventy consecutive consenting patients with IBD (62 ulcerative colitis [UC], 8 Crohn’s disease [CD]; 40 males, mean age [SD] 36.2 [11.3] years) and 100 healthy volunteers (44 males, age 31.22 [SD] [10.5] years) as controls were enrolled. All participants were directed to take self-assessment tests, Patient Health Questionnaire -9 (PHQ-9) and Symptom Checklist Anxiety Scale (SCL-A20). Participants having a score ≥ 10 on PHQ-9, or ≥ 29 on SCL-A20 were administered the Hamilton Depression Rating Scale (HAM-D) or Hamilton Anxiety (HAM-A) scales, respectively. The severity of depression and anxiety was graded with HAM-D and HAM-A scales, respectively. The protocol was approved by the Institutional Ethics Committee.

Results

The prevalence of depression (34.3% vs. 5%, p?<?0.0001, OR 9.7) and anxiety (18.6% vs. 2%, p?=?0.0002, OR 11.17) was higher in patients with IBD as compared to controls. The severity of depression was higher in patients compared to controls (mean rank 17 vs. 7, p?=?0.04). The prevalence of depression was not different between UC and CD; all IBD patients with anxiety had UC. The mean duration of disease and history of corticosteroid treatment or surgery for IBD were not associated with the presence of depression or anxiety. Patients with severe CD (Crohn’s disease activity index, CDAI?>?450) had more severe depression. The severity of UC did not correlate with severity of anxiety or depression in UC.

Conclusions

Anxiety and depression are more prevalent in IBD patients as compared to healthy individuals.

     

Assessing Health Status in Inflammatory Bowel Disease Using a Novel Single-Item Numeric Rating Scale

Background

Current instruments used to measure disease activity and health-related quality of life in patients with Crohn’s disease (CD) and ulcerative colitis (UC) are often cumbersome, time-consuming, and expensive; although used in clinical trials, they are not convenient for clinical practice. A numeric rating scale (NRS) is a quick, inexpensive, and convenient patient-reported outcome that can capture the patient’s overall perception of health.

Aims

The aim of this study was to assess the validity, reliability, and responsiveness of an NRS and evaluate its use in clinical practice in patients with CD and UC.

Methods

We prospectively evaluated patient-reported NRS scores and measured correlations between NRS and a range of severity measures, including physician-reported NRS, Crohn’s disease activity index (CDAI), Harvey-Bradshaw index (HBI), inflammatory bowel disease questionnaire (IBDQ), and C-reactive protein (CRP) in patients with CD. Subsequently, we evaluated the correlation between the NRS and standard measures of health status (HBI or simple colitis clinical activity index [SCCAI]) and laboratory tests (sedimentation rate [ESR], CRP, and fecal calprotectin) in patients with CD and UC.

Results

The patient-reported NRS showed excellent correlation with CDAI (R ² = 0.59, p < 0.0001), IBDQ (R ² = 0.66, p < 0.0001), and HBI (R ² = 0.32, p < 0.0001) in patients with CD. The NRS showed poor, but statistically significant correlation with SCCAI (R ² = 0.25, p < 0.0001) in patients with UC. The NRS did not correlate with CRP, ESR, or calprotectin. The NRS was reliable and responsive to change.

Conclusions

The NRS is a valid, reliable, and responsive measure that may be useful to evaluate patients with CD and possibly UC.     

Presence of intestinal Mycobacterium avium subspecies paratuberculosis (MAP) DNA is not associated with altered MMP expression in ulcerative colitis

Background

Mycobacterium avium subspecies paratuberculosis (MAP) is suspected to be a causative agent in human Crohn's disease (CD). Recent evidence suggests that pathogenic mycobacteria and MAP can induce the expression of Matrix Metalloproteinases (MMP), which are the main proteases in the pathogenesis of mucosal ulcerations in inflammatory bowel disease (IBD). Within this study we assessed the prevalence of intestinal MAP specific DNA in patients with Crohn's disease, ulcerative colitis (UC), and healthy controls. We further analysed regulation patterns of MMPs in mucosal tissues of UC patients with and without intestinal MAP DNA detection.

Methods

Colonic biopsy samples were obtained from 63 Norwegian and German IBD patients and 21 healthy controls. RNA was quantified by quantitative real-time polymerase chain reaction (PCR) to study MMP gene expression in both pathological and healthy mucosal specimens. The presence of MAP DNA in colonic mucosa was examined using MAP specific PCR.

Results

MAP DNA was detected in 20% of UC patients and 33% of healthy controls but only in 7% of patients with CD. UC patients treated with corticosteroids exhibited a significantly increased frequency of intestinal MAP DNA compared to those not receiving corticosteroids. Expression of MMP-1, -2, -7, -9, -13, -19, -28 and TNF-α did not differ between UC patients with presence of intestinal MAP DNA compared to those without. MMP-2, MMP-9 and MMP-13 were significantly decreased in UC patients receiving corticosteroids.

Conclusions

The presence of intestinal MAP specific DNA is not associated with altered MMP expression in UC in vivo. Corticosteroids are associated with increased detection of intestinal MAP DNA and decreased expression of certain MMPs. Frequent detection of MAP DNA in healthy controls might be attributable to the wide environmental distribution of MAP and its presence in the food-chain.     

How fast up the ladder? Factors associated with immunosuppressive or anti-TNF therapies in IBD patients at early stages: results from a population-based cohort

Background

With the introduction of anti-TNF therapies in the treatment of IBD, the therapeutic strategies have changed to an accelerated step-up care to avoid long-term complications. Little is known about the implementation of these strategies into daily care. We aimed to evaluate this question and to identify factors associated with the early use of immunosuppressants or anti-TNF therapies in a population-based IBD cohort.

Methods

Patients with an IBD diagnosed between January 2004 and December 2008 were included. Medical therapies were evaluated at first diagnosis and during a 5-year follow-up. Risk factors associated with the initiation of an immunosuppressive therapy were assessed.

Results

Two hundred and forty-one patients were evaluated (145 Crohn’s disease (CD), 96 ulcerative colitis (UC)). An immunosuppressive or anti-TNF therapy was started in 83 CD (57.2 %) and 40 UC (43 %) patients (p?=?0.033, relative risks (RR) 1.77; 95 % confidence interval (CI) 1.05–3.0). After 5 years, 38.8 % CD patients on immunosuppressive therapy were treated with anti-TNF therapies. The use of corticosteroids at first diagnosis, disease localization and surgery were independent predictors for an immunosuppressive or anti-TNF therapy in CD. In UC, the extension of disease was associated with immunosuppressive therapies. The use of steroids and localization in CD patients and an extended disease in UC patients affected the time until an immunosuppressive therapy was started.

Conclusion

We found a high proportion of patients using an immunosuppressive therapy during the early course. Therefore, the accelerated step-up strategy seems to be successfully implemented in the daily care of IBD patients. We were able to identify several factors associated with an immunosuppressive or anti-TNF therapy in CD and UC.     

Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea

Objective: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn’s disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard.

Methods: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed.

Results: Diagnostic outcome: normal: n?=?46 (73%), CC: n?=?9 (14%), LC: n?=?4 (6%), UC: n?=?2 (3%), CD: n?=?2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p?=?0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S-EPX and S-ECP between the groups.

Conclusion: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome.     

Effect of Follow-Up Endoscopy on the Outcomes of Patients with Inflammatory Bowel Disease

Background

Little is known about the role of follow-up endoscopy in patients with inflammatory bowel disease (IBD).

Aim

The present study aimed to evaluate whether repeated endoscopies would be beneficial in improving outcomes of patients with IBD.

Methods

Patients who had been initially confirmed to have IBD at two tertiary hospitals in Korea were regularly followed and included in this study. The clinical impact as assessed by the presence or absence of a change in management after endoscopy and cumulative hospitalization rate was compared between two groups classified according to the presence or absence of indications.

Results

A total of 188 patients with IBD were enrolled [69 patients with Crohn’s disease (CD) and 119 with ulcerative colitis (UC)]. Of these patients, 130 underwent follow-up endoscopy (48 with CD and 82 with UC). The rate of management change was significantly higher in the group with indications for follow-up endoscopy (p = 0.001 in CD and <0.001 in UC). The presence of any indications for follow-up endoscopy was found to be a significant predictor of hospitalization risk in patients with UC (p = 0.015), but not in those with CD. However, there was no significant difference in cumulative hospitalization hazard with respect to treatment change in patients without any endoscopic indications (p = 0.561 in CD and 0.423 in UC).

Conclusions

Follow-up endoscopy might not have a significant impact on the overall clinical course and outcomes in patients with IBD. However, the presence of endoscopic indications predicts a poor clinical outcome in UC.     

Effects of family history on inflammatory bowel disease characteristics in Japanese patients

Background

Although the prevalence of inflammatory bowel disease (IBD) is reported to have reached a plateau in Western countries, it is increasing in Asia. The etiology of IBD is still under investigation. We performed an epidemiological study to clarify the characteristics of IBD in Japan, focusing on patients’ family history.

Methods

We obtained clinical data on ulcerative colitis (UC) (46,114 cases) and Crohn’s disease (CD) (11,305 cases) in 2007 from an electronic database maintained under the Japanese Ministry of Health, Labour and Welfare’s nationwide registry system, and analyzed the differences in disease characteristics between patients with IBD who had a family history of the disease and those who did not.

Results

A total of 2.7% of the patients with UC and 2.6% of those with CD had a family history. The present age and age at disease onset were lower among the patients with UC who had a family history than among those without (present age: p?p?U-test), but no similar trend was observed in the patients with CD. Disease severity was worse among both the UC and CD patients with a family history. The clinical course of patients with UC was not affected by family history. Levels of independence in daily life were associated with family history among CD patients, whereas age was associated with levels of independence in daily life among UC patients.

Conclusion

Disease characteristics of IBD vary in some aspects according to the presence or absence of a family history.     

Serum Metabolic Profiling in Inflammatory Bowel Disease

Background

The inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract whose pathogenesis is not completely understood. ¹H nuclear magnetic resonance (NMR) spectroscopy of serum generates comprehensive metabolic profiles, reflecting systemic metabolism, which may be altered in disease states.

Aim

The aim of this study was to use ¹H NMR-based serum metabolic profiling in the investigation of CD patients, UC patients, and controls, potentially to provide insights into disordered metabolism in IBD, and into underlying mechanisms of disease.

Methods

Serum metabolic profiles were acquired from 67 individuals (24 CD patients, 20 UC patients, and 23 healthy controls). The multivariate pattern-recognition techniques of principal components analysis (PCA) and partial least squares discriminant analysis with orthogonal signal correction (OSC-PLS-DA) were used to investigate differences between cohorts.

Results

OSC-PLS-DA distinguished CD and UC cohorts with significant predictive accuracy, highlighting differences in lipid and choline metabolism. Metabolic profiles of both CD and UC cohorts, and the combined IBD cohort, differed significantly from controls: metabolites of importance in the OSC-PLS-DA models included lipoproteins (especially HDL cholesterol), choline, N-acetylglycoprotein, and amino acids.

Conclusions

¹H NMR-based metabolic profiling has identified distinct differences in serum metabolic phenotype between CD and UC patients, as well as between IBD patients and controls.     

Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity

Background

Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease.

Methods

Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn’s disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS).

Results

Serum NGAL levels were elevated in IBD patients (88.19?±?40.75?ng/mL) compared with either HC (60.06?±?24.18?ng/mL) or IBS patients (60.80?±?20.30?ng/mL), P?P?Conclusions Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.     

Reduced hydrophobicity of the colonic mucosal surface in ulcerative colitis as a hint at a physicochemical barrier defect

Purpose

There is increasing evidence that a defect of the gastrointestinal mucosal barrier is important for the development of inflammatory bowel diseases (IBD). The hydrophobicity of the colonic mucosal surface is a measure of its resistance to luminal antigens, e.g. of bacterial origin. Therefore, the purpose of this study was to determine this parameter in patients suffering from IBD.

Methods

Nineteen patients with ulcerative colitis (UC), ten patients with Crohn??s disease (CD) and 20 controls were examined. All underwent colonic surgery at the University Hospital Heidelberg. Clinical disease activity was determined. From every subject, colonic tissue specimens were obtained, and hydrophobicity of the mucosal surface was determined with a goniometer by multiple plateau contact angle measurements. Histological evaluation of disease activity was performed in directly adjacent tissue specimens.

Results

Hydrophobicity of the colonic mucosal surface, expressed as plateau contact angles, was significantly reduced in patients with UC (mean?±?SEM, 47.8°?±?3.4°) compared to those with CD (72.0°?±?5.2°) and controls (72.5°?±?5.6°; over-all P?=?0.0004; UC versus controls, P?P?P?>?0.05). Between mucosal hydrophobicity and clinical disease activity, as well as mucosal hydrophobicity and histological disease activity, no significant correlation was found.

Conclusions

The results suggest a defective physicochemical barrier as an essential factor in the pathogenesis of UC, but not CD. The fact that no correlation was found between mucosal hydrophobicity and disease activity may indicate that the loss of mucosal hydrophobicity in UC is not exclusively a secondary effect due to inflammation.