Chronic Inflammatory Bowel Disease Patients Research Articles

Knowledge of Chronic Inflammatory Bowel Disease Patients about Their Disease in the North Moroccan Region

Patients' level of knowledge about their disease plays an essential role in therapeutic management, by facilitating patients' acceptance of the diagnosis, their active participation in treatment and improved compliance. Few studies have been conducted in Morocco to assess the level of knowledge of IBD patients. The aim of this study was to assess the level of knowledge of IBD patients in the northern region of Morocco. Materials and methods: We conducted a cross-sectional study over a period of 5 months in the hepato-gastroenterology department of the Mohammed VI University Hospital in Tangiers. Our study involved a series of 100 patients with confirmed IBD. A questionnaire was drawn up and given to the patients. Results: The main results of our study reveal a considerable lack of knowledge among our patients about their disease, covering all areas of the disease and more specifically the treatment and complications aspect. This lack of knowledge can be attributed in part to the high rate of illiteracy in our setting. Conclusion: These results underline the importance of raising patients' awareness of their disease by setting up educational workshops tailored to their level of understanding. These workshops aim to improve patients' knowledge, encourage adherence to treatment and, ultimately, improve their quality of life. Keywords: Inflammatory bowel diseases, patient knowledge

Role of MR enterography versus ileo-colonoscopy in the assessment of inflammatory bowel diseases

BackgroundInflammatory bowel disease (IBD) is widespread and rapidly rising in developing countries. It remains a significant issue in Western culture with a prevalence of more than 0.3%. Symptom control has been the only focus of treatment before the discovery that many individuals with IBD continue to have disease activity even in the absence of clinical symptoms. Therefore, treatment goals now include establishing clinical remission, steroid-free remission, and mucosal healing, which may eventually be complemented by transmural healing in cross-sectional imaging modalities. Magnetic resonance enterography (MRE), computed tomography enterography, and small-bowel ultrasound are now reliable methods for staging intramural lesions and extramural consequences in CD and for determining disease activity and severity. Recently literature suggests the incorporation of (MRE) for periodic reevaluation of IBD patients, as it offers small-bowel, colonic, and extra-enteric assessment as well as monitors the response to the anti-inflammatory therapy. The purpose of the current study was to compare MRE with ileo-colonoscopy findings in the diagnosis of IBD features, specifically Crohn's disease, and ulcerative colitis, as well as in the detection of disease exacerbation (Activity).ResultsThis study used MRE and ileo-colonoscopy to assess chronic inflammatory bowel disease patients; the patient population (n = 30) was made up of (14/30, 46.7%) females and (16/30, 53.3%) males, with a mean age of 32 ± SD 13 years. MRE alone detected lymphadenopathy in 73.3% of patients, and mural thickening with a mean of 4.1 ± SD 5.1 mm. It has detected mucosal enhancement with 80% sensitivity and 60% specificity. However, it was unable to detect mucosal erosions or ulceration.ConclusionsMRE is sensitive, inexpensive, noninvasive, and radiation-free for inflammatory bowel disease detection, with 86.7% diagnostic accuracy for affected areas. Unlike ileo-colonoscopy, it could examine the entire small intestine, precisely measure the affected loop, and detect activity signs such as mural thickening and lymphadenopathy. Only ileo-colonoscopy could detect mucosal degradation and superficial ulcers. IBD treatment protocols should incorporate MRE for small-bowel, colonic, and extra-enteric assessment, monitoring of disease activity, and anti-inflammatory therapy response.

Стан судинного ендотелію у пацієнтів з хронічними запальними захворюваннями кишечника i різним нутритивним статусом

Актуальність. Визначення ендотеліальної функції за допомогою неінвазивних методів відіграє основну роль у прогнозуваннi перебігу різних захворювань, ризику розвитку ускладнень та оцінцi лікування. Мета: оцінка ендотеліальної функції в пацієнтів iз хронічними запальними захворюваннями кишечника (ХЗЗК) залежно від їхнього нутритивного статусу шляхом визначення стану судинного ендотелію в пробі з реактивною гіперемією та вмісту метаболітів оксиду азоту (МОА) в сироватці крові. Матеріали та методи. Сто двадцять пацієнтів iз ХЗЗК (81 — iз неспецифічним виразковим колітом (НВК) та 39 пацієнтів із хворобою Крона (ХК)) були розподілені на групи залежно від антропометричних характеристик: І — зі зниженим нутритивним статусом (n = 70); ІІ — iз нормальним (n = 20); ІІІ — iз підвищеним нутритивним статусом (n = 30). У сироватці крові пацієнтів вимірювали рівень МОА за В.А. Метельською. Для оцінки ендотеліальної функції визначали ендотелійзалежну вазодилатацію плечової артерії в пробі з реактивною гіперемією. Результати. На основі проведених досліджень встановлено вірогідне зниження вмісту МОА в сироватці крові: у пацієнтів iз НВК — у 1,7 раза (р < 0,01) та з ХК — в 1,9 раза (р < 0,001). Зниження вмісту МОА в сироватці крові не залежало від нутритивного статусу пацієнтів iз ХЗЗК. Порушення функції судинного ендотелію виявлено в 76,7 % випадків: зниження функції ендотелію — у 49,2 %, дисфункція — у 27,5 %. Зміни функції судинного ендотелію зареєстровано в 75,7 % пацієнтів І групи, 75 % — ІІ та у 83,4 % пацієнтів ІІІ групи, переважно внаслiдок зниження функції ендотелію. Висновки. Показано, що в 71 % пацієнтів iз ХЗЗК відбувається вірогідне зниження вмісту МОА в сироватці крові, що не залежить від їхнього нутритивного статусу. У хворих iз НВК спостерігалися більш виражені зміни у частотi виявлених порушень та більш значне зростання діаметра плечової артерії порівняно iз пацієнтами з ХК. Зниження нутритивного статусу супроводжувалося змінами функції судинного ендотелію в 75,4 % випадків.

Healthcare resource utilization and treatment costs of Finnish chronic inflammatory bowel disease patients treated with infliximab

Objectives: Inflammatory bowel disease (IBD) is associated with a high economic burden to society due to its early onset and chronic character. Here, we set out to characterize healthcare resource utilization and associated costs in Crohn’s disease (CD) and ulcerative colitis (UC) patients with infliximab treatment, the most widely used first-line biologic agent in Finland, in a real-world clinical setting.Methods: This was a retrospective, non-interventional single-center study. Infliximab was administered in routine care, and data were collected retrospectively from electronic health records. All adult anti-TNF naïve CD or UC patients whose infliximab treatment was initiated at the Hospital District of Southwest Finland between the years of 2014 and 2016 were included in the study. Each patient was followed-up for 12 months after the initiation of infliximab treatment.Results: A total of 155 patients were included (45 CD, 110 UC). Altogether, 60.0% (n = 27) of all CD patients and 43.6% (n = 48) of all UC patients persisted on infliximab therapy 12 months after treatment initiation. The total cost was similar for both CD and UC cohorts (CD, €10,243; UC, €10,770), infliximab treatment being the highest individual cost (60.3% of the total cost in CD; 53.4% in UC). The mean number of infliximab infusions during the 12-month follow-up was 7.0 for CD and 6.5 for UC patients.Conclusions: IBD causes a significant burden to the Finnish healthcare system. This study provides a detailed characterization of the cost landscape of IBD and contributes to optimizing treatment strategies and healthcare resource use in the biosimilar era.

A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF.

Background. The production of anti-drug antibodies (ADAs) against IgG monoclonal antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene could be involved in anti-TNF ADA generation and treatment resistance. Material and Methods. A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum level of both anti-TNFs (infliximab or adalimumab) and ADA against them were measured. Results. No significant differences were observed between ADA occurrence or V158F genotype and type of disease or the kind of anti-TNF administrated. Interestingly, VV genotype correlated with patients producing ADA (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of this event after multivariate analysis. Moreover, VV genotype also correlated with those patients receiving anti-TNF dose intensification (p=0.03). Conclusion. FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs and it could be taken into account when considering the dose and type of anti-TNF in IBD patients.

Endoscopic Therapeutic Approach for Dysplasia in Inflammatory Bowel Disease.

Long-standing intestinal inflammation in patients with inflammatory bowel disease (IBD) induces dysplastic change in the intestinal mucosa and increases the risk of subsequent colorectal cancer. The evolving endoscopic techniques and technologies, including dye spraying methods and high-definition images, have been replacing random biopsies and have been revealed as more practical and efficient for detection of dysplasia in IBD patients. In addition, they have potential usefulness in detailed characterization of lesions and in the assessment of endoscopic resectability. Most dysplastic lesions without an unclear margin, definite ulceration, non-lifting sign, and high index of malignant change with suspicion for lymph node or distant metastases can be removed endoscopically. However, endoscopic resection of dysplasia in chronic IBD patients is usually difficult because it is often complicated by submucosal fibrosis. In patients with dysplasias that demonstrate submucosa fibrosis or a large size (≥20 mm), endoscopic submucosal dissection (ESD) or ESD with snaring (simplified or hybrid ESD) is an alternative option and may avoid a colectomy. However, a standardized endoscopic therapeutic approach for dysplasia in IBD has not been established yet, and dedicated specialized endoscopists with interest in IBD are needed to fully investigate recent emerging techniques and technologies.

Potential Association Between TLR4 and Chitinase 3-Like 1 (CHI3L1/YKL-40) Signaling on Colonic Epithelial Cells in Inflammatory Bowel Disease and Colitis-Associated Cancer

Inflammatory bowel disease (IBD) is a group of inflammatory disorders in the small and large intestines. Several studies have proved that persistent and disregulated host/microbial interactions are required for the development of IBD. It is well known that chronic IBD is strongly associated with an increased risk of developing colorectal cancer by 0.5-1% annually, 8-10 years after the initial diagnosis. To detect the tiny dysplasia or early stage of cancer in chronic IBD patients, a tremendous amount of effort is currently directed for improving colonoscopic technology and noninvasive serological marker development. However, there is only a limited amount of data available to understand the exact mechanism of how long term chronic colitis is connected to the development of colorectal tumors. Recently, our group has identified significantly increased expression of chitinase 3-like 1 (CHI3L1) molecule in non-dysplastic mucosa from patients with IBD and remote dysplasia/cancer, compared to patients with IBD without dysplasia or healthy controls. CHI3L1 seems to contribute to the proliferation, migration, and neoplastic progression of colonic epithelial cells (CECs) under inflammatory conditions. Furthermore, the TLR4-mediated intracellular signaling cascade is likely to interact with CHI3L1 signaling in CECs. In this review article, we have concisely summarized the cellular and molecular mechanisms underlining the development of IBD and colitis-associated cancer, with particular focus on the TLR4- and CHI3L1-signaling pathways in CECs.

Extraintestinal Manifestations in a Single Centre Cohort of Chronic Inflammatory Bowel Disease Patients

Extraintestinal Manifestations in a Single Centre Cohort of Chronic Inflammatory Bowel Disease Patients

The Relationship between Quiescent Inflammatory Bowel Disease and Peripheral Polyneuropathy

Inflammatory bowel disease is a chronic, recurrent disorder that involves multiple organ systems. Polyneuropathy is the most common neurological manifestation. The aim of the present study was to investigate the relationship between polyneuropathy and inflammatory bowel disease. The study included 40 patients with infl ammatory bowel disease (20 with ulcerative colitis and 20 with Crohn's disease) and 24 healthy controls. The patients had no clinical signs or symptoms of polyneuropathy. Nerve conduction studies were performed using an electroneuromyography apparatus. Mean distal motor latencies, conduction velocities, and F wave minimum latencies of the right median nerve were signifi cantly abnormal in the patient group, compared to the healthy controls (p<0.05). Some electrophysiological alterations were observed in chronic inflammatory bowel disease patients who showed no clinical signs. While investigating extra-intestinal manifestations in inflammatory bowel disease patients, nerve conduction studies must be performed to identify electrophysiological changes and subclinical peripheral polyneuropathy, which can subsequently develop.

Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients

Dysbiosis of the gut mucosa-associated microbiota (MAM) plays a pivotal role in the pathogenesis of chronic inflammatory bowel diseases (IBD). To date, dysbiosis only describes the altered composition of the different bacterial populations, but little is known about transcriptional activity, metabolism and the 'live' status of the MAM. In this study we investigated the transcriptional activity of the dominant intestinal bacterial populations in patients with IBD. Colonic mucosal biopsies from patients with active Crohn's disease (CD; n=10), active ulcerative colitis (UC; n=10) and healthy individuals (HI; n=10) were compared by 16S rRNA gene and rRNA profiles using clone libraries with more than 1700 sequenced clones. Bacterial richness was significantly lower in clone libraries based on rRNA compared to those based on the rRNA genes in the CD group (3.01 vs 3.91) and the UC group (3.61 vs 4.15), but showed no difference in HI (3.81 vs 3.85). The qualitative composition of rRNA and rRNA gene clone libraries was significantly different, with the phylum Bacteroidetes being the most active (P<0.01) compared to other populations in all clinical groups. In contrast, Actinobacteria and Firmicutes were inactive in the CD group, while Escherichia sp. were both abundant and active in the CD and UC groups. Most of the phylotypes showing the highest activity index ratios represented less than 1 % of the microbiota. Our findings indicate that specific bacterial populations are activated in IBD patients, while other groups are in an inactive or 'dormant' state. The transcriptional activity points to a more functional role of the intestinal mucosal microbiota and may lead to the identification of therapeutic targets in the active modulation of microbial factors.

Infliximab Pharmacokinetics in Inflammatory Bowel Disease Patients

Infliximab, a chimeric monoclonal antibody, has profoundly modified the treatment of several inflammatory diseases, but no satisfactory description of its pharmacokinetics is available. The objective of this study is to describe the pharmacokinetics of infliximab and to explore the sources of its interindividual variability. Thirty-three chronic inflammatory bowel disease patients were studied. Infliximab serum concentrations, obtained during therapeutic drug monitoring, were analyzed using a population approach. Influence of sex, weight, age, concomitant immunosuppressive treatment, and development of antibodies toward infliximab (ATI) on pharmacokinetic parameters was investigated. A two-compartment model with first-order distribution and elimination constants allowed a satisfactory description of infliximab serum concentrations. Mean population distribution and elimination half-lives were 4.3 and 18.5 days, respectively. Weight and sex were found to significantly influence volume of distribution of the central compartment, which increased with weight and was higher in men. Clearance was 2.7 times higher, and elimination half-life was 34% lower in the presence of ATI. In two patients, an increase in infliximab dose or a decrease in dosing interval lead to a decrease in infliximab clearance toward its value in patients without ATI. Infliximab pharmacokinetics are similar to those of other monoclonal antibodies, notably with an elimination half-life of approximately 3 weeks. Both body weight and sex were found to influence infliximab pharmacokinetics, and its clearance increased thrice in the presence of ATI.

Psychotherapy with chronic inflammatory bowel disease patients: A Review

Two distinct factors have lead in the past to the development of several psychotherapeutic treatments for patients with inflammatory bowel diseases (IBD). First, clinicians and researchers believe that psychologic and somatic factors in chronic IBD, Crohn's disease, and ulcerative colitis) are connected. In addition, IBD reduces the health-related quality of life for these patients. The purpose of the psychotherapies is to influence the somatic course of the disease, the psychological state of the patients, or the patients' health related quality of life. This report evaluates the existing studies with regard to the effectiveness of psychotherapy IBD patients received in addition to medical treatment. We have identified 10 psychotherapy studies and 4 additional studies on self management and patient education on this topic. The studies significantly differ from each other in regard to psychotherapeutic methods, inclusion criteria, and outcome assessments. The results so far lead to the conclusion that psychotherapy does not have an impact on the course of the disease but, in some cases, positively influences the patient's psychologic state (such as depression, anxiety, and health related quality of life or coping with the disease). Thus, psychotherapy cannot, in general, be recommended for all patients with chronic IBD. Patients, however, that display a tendency toward psychologic problems, especially as it pertains to their illness, might profit from it.

Low free and total insulinlike growth factor I (IGF-I) and IGF binding protein-3 levels in chronic inflammatory bowel disease: partial normalization during prednisolone treatment

OBJECTIVES: Catabolism and growth impairment are well known complications of chronic inflammatory bowel disease (CIBD). This may be caused by disease activity itself and/or the medical treatment, which may lead to changes in the growth hormone and insulinlike growth factor I (IGF-I) axis. Interest has focused on corticosteroids, as they are known to influence the growth hormone/IGF-I axis. METHODS: The aim of the present study was to examine changes in total and free IGF-I, IGF binding proteins (IGFBPs), and IGFBP-3 protease activity in 10 patients with severe acute activity in colon CIBD before and during high dose prednisolone treatment (1 wk) and 3 months tapering. Eight healthy subjects served as controls. RESULTS: Total and free IGF-I were significantly reduced by 35% and 53%, respectively, before prednisolone treatment ( p < 0.05), and free IGF-I remained reduced even by the end of the study period relative to controls ( p < 0.05). IGFBP-3 was reduced by 16% before ( p < 0.05), with normalization during prednisolone treatment and tapering relative to controls. There was no evidence of increase in IGFBP-3 protease activity. IGFBP-1 was increased before and tended also to be increased during prednisolone treatment and tapering. CONCLUSIONS: Marked changes in serum total and free IGF-I and IGFBPs were demonstrated in patients with severe exacerbation of CIBD without complete normalization during high dose prednisolone treatment and tapering. These changes may partly be involved in the catabolism of active CIBD patients.

Assay, Isolation and Characterization of Circulating Immune Complexes from Serum of Gastrointestinal Cancer, Stage III and IV Melanoma and Chronic Inflammatory Bowel Disease Patients

Circulating immune complexes (CIC) have been detected in several autoimmune diseases, and studies have also suggested that CIC provide a useful tool as tumor markers. In order to identify differences or similarities in antigenic composition, CIC from 23 patients with gastrointestinal (GI) tumors, from 20 patients with stage III and IV melanoma and from 6 patients with inflammatory bowel disease (IBD) were studied. Serum from all GI, melanoma and IBD patients showed higher levels of CIC than controls. SDS/PAGE electrophoresis under reducing conditions revealed some differences between cancer and IBD patients as far as the CIC protein composition was concerned. In melanoma patients, two fast-migrating bands, in the regions of 71-74 and 30-49 kD, were found, consistent with previously isolated and characterized antigens described in the literature.

Serum interferon activity in inflammatory bowel disease. Arachidonic acid release and lipoxygenation activated by alpha-class interferon in human neutrophils.

Serum interferon (IFN) of alpha-class was studied in 64 consecutive patients, 26 with Crohn's disease, 38 with ulcerative colitis, and in 34 healthy volunteers. Detectable IFN-alpha in 10 patients was associated with a moderate to severe activity of chronic inflammatory bowel disease (CIBD). However, 19 of 28 patients (68%) with activity in their disease did not have elevated IFN-alpha levels. The three groups, ulcerative colitis, Crohn's disease, and healthy volunteers did not reveal any statistically significant difference in serum IFN-alpha, as four of 34 healthy controls without intercurrent infections had elevated levels as well. Possible effects of alpha, beta, and gamma classes of IFN on endogenous arachidonic acid (AA) release and metabolism in human neutrophils was investigated in a substudy. IFN-alpha caused a dose-dependent release of AA from phospholipids and metabolism of a modest fraction of leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) at doses reaching a maximum of 100 IU/ml. IFN of the beta and gamma classes did not exert such effects. Addition of complement 5a to cells activated by IFN-alpha caused induction of increased 5-lipoxygenase activity with unchanged release of AA. As only 16% of all CIBD patients had elevated IFN-alpha levels as compared to 12% among the group of healthy volunteers, IFN-alpha does not seem to be of importance for the perpetuation of the inflammatory reaction in ulcerative colitis or Crohn's disease, and other factors may therefore be responsible for activation of the inflammatory cells to production of LTB4 and 5-HETE.

Zinc status and its relation to growth retardation in children with chronic inflammatory bowel disease

Zinc status was studied in 30 patients with chronic inflammatory bowel disease (CIBD) as well as in 17 normal children, 13 primordial short stature, and 17 anorexia nervosa patients. Basal serum and urinary excretion levels of zinc were measured in all patients. In addition, a zinc loading test was performed in 16 CIBD patients, 21 normal and/or short stature children, and nine patients with anorexia nervosa. Eleven of 30 patients with CIBD had serum zinc values less than 0.7 microgram/ml, whereas none of the other patients had hypozincemia. In addition, the mean urinary zinc excretion of CIBD patients was significantly lower than that of patients with primordial short stature and with anorexia nervosa. An altered response to oral zinc load was the most frequent abnormality in CIBD patients. Those with moderate and severe clinical disease activity had a decreased serum rise of zinc after the oral load of this ion. Urinary excretion of zinc after oral load was also marked by deficiency in all CIBD patients. The abnormalities of zinc metabolism were more frequent among the CIBD patients with growth abnormalities, although they were also found in patients who had normal growth. Among the 14 patients with CIBD and growth abnormalities, seven were hypozincemic and four hypozincuric. Hypozincemia was only found in four patients who had normal height; however, the growth velocity was not known. The zinc tolerance test revealed abnormalities in four of five CIBD patients with short stature and in two of three patients with slow growth. On the other hand, similar alterations in zinc tolerance tests were seen in three of seven CIBD patients with normal height and growth.

Serum Immunoglobulin M Concentrations Following Bowel Resection in Chronic Inflammatory Bowel Disease

Serum immunoglobulin alterations were characterized in 20 patients with chronic inflammatory bowel disease (CIBD) undergoing bowel resection and in 11 control subjects undergoing intra-abdominal operations. Serum immunoglobulin M (IgM) values became elevated during the 2nd week in both groups with individual serum IgM concentrations reaching as high as 9 times preoperative values. The IgM increment, which was 19 S polyclonal immunoglobulin, was significantly greater in the CIBD group than in controls. Because of a recent suggestion that this IgM rise might be related to the pathogenesis of CIBD, the affinity of this IgM for colon was studied in two ways. Serum anticolon antibody titers did not change after surgery nor did IgM, isolated from serum after surgery and labeled with 125I, bind to homogenates of normal or CIBD colon. Titers of heterophile antibody and antibodies directed against Escherichia coli, Bacteroides, and blood group antigens increased in many patients. In most instances, these increments were shown to be antibody of the IgM class by reduction with 2-mercaptoethanol. These data indicate that the IgM changes after abdominal surgery (1) are not specific for CIBD patients, (2) do not represent antibody directed against colon antigens, and (3) include increased titers of several IgM antibodies. These findings might be explained by a response to bacterial or tissue antigens released at or after the time of surgery.