Urban–rural environmental exposure during childhood and subsequent risk of inflammatory bowel disease: a meta-analysis

Background: The relationship between living conditions in urban and rural areas during childhood and subsequent inflammatory bowel disease (IBD) remains controversial.

Aim: To explore the association between environmental exposures early in life and the subsequent risk of IBD.

Methods: Literature searches were conducted in the following databases: PubMed, EMBASE, and Conference Proceedings Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds ratios (ORs) with 95% confidence intervals.

Results: The search strategy identified 15 studies. Of these, 9 studies explored the association between urban exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies explored this relationship with Crohn’s disease (CD) and IBD, respectively. A meta-analysis showed that the pooled ORs estimated for the case–control studies of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11, 1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed significant relationships between CD and living conditions in case–control studies published during 2010–2017 and in non-European countries (P < 0.05).

Conclusions: Living conditions during childhood are positively associated with the subsequent development of IBD. Urban living environment is more common among those with CD than UC.     

Antibiotics exposure and risk of inflammatory bowel disease: a systematic review

Aim: The aim of this study was to critically assess all available evidence suggesting an association between antibiotic exposure and new onset of inflammatory bowel disease (IBD).

Materials and methods: This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of PubMed, Embase and the Cochrane Library. Data on patient demographics, antibiotic exposure and confounding factors were analyzed. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of eligible studies.

Results: A total of 15 observational studies (10 case control and five cohort) including 8748 patients diagnosed with IBD were systematically reviewed. Antibiotic exposure was mostly associated with Crohn’s disease but not with ulcerative colitis. In particular, penicillin’s, cephalosporins, metronidazole and fluoroquinolones were most commonly associated with the onset of Crohn’s disease. The impact of tetracycline-family antibiotics on the pathogenesis of IBD was not clear.

Conclusion: There may be an association between antibiotic exposure and the development of IBD; especially Crohn’s disease. Even though, clinicians should be cautious when prescribing certain antibiotic regimens to patients with a strong family history of IBD, it should be emphasized that available data are not granular enough to reach any definitive conclusions.     

Intestinal colonization with phylogenetic group B2 Escherichia coli related to inflammatory bowel disease: a systematic review and meta-analysis

Abstract

Background and objectives. Increased numbers of Escherichia coli and, furthermore, specific subtypes of E. coli, such as E. coli of the phylogenetic groups B2 and D have been found in the intestine of patients with inflammatory bowel disease (IBD). In this review, we wanted to evaluate the relationship between B2 and D E. coli intestinal colonization and IBD. Methods. A systematic review with meta-analyses. We included studies comparing colonization with B2 and D E. coli in IBD patients and in controls. Random-effects and fixed-effect meta-analyses were performed. Results. We included 7 studies on 163 patients with IBD and 89 controls. Among IBD patients, 57 patients had ulcerative colitis (UC) and 95 Crohn’s disease (CD). Random-effects meta-analysis showed that IBD patients were more likely to have B2 E. coli intestinal colonization compared with controls (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.25–4.16). There was little between-study heterogeneity (I² = 0). The result was confirmed in subgroup analyses of patients with UC (OR: 3.58; 95% CI: 1.62–7.90), but not CD (OR: 1.94; 95% CI: 0.98–3.82). Intestinal colonization with phylogenetic group D E. coli was not found to be related to IBD, UC or CD. Conclusions. Our study reveals that intestinal colonization with phylogenetic group B2 E. coli is associated with UC. Due to the design, we are unable to determine if the colonization with B2 E. coli leads to the development of the disease or the disease increases the risk of colonization with B2 E. coli.     

Epidemiology of inflammatory bowel disease in South America: A systematic review

BACKGROUND The worldwide epidemiology of inflammatory bowel disease(IBD) is rapidly changing. Increasing Crohn's disease(CD) and ulcerative colitis(UC) incidence and prevalence have been recorded in developing regions such as Asia, Africa and Eastern Europe where it was previously thought to be uncommon. Whether this is also the case in South America is not well known. Demonstration that developing regions worldwide have increasing IBD incidence would indicate that environmental change plays a significant role in the development of IBD.AIM To report the incidence, prevalence and disease characteristics of CD and UC within the South American continent.METHODS A systematic review was conducted by searching published studies in major international and regional databases(MEDLINE, EMBASE and Scopus) between January 1990 and December 2018. Outcomes considered were incidence,prevalence, phenotype, environmental and genetic factors, ethnicity and gender.A pair of independent reviewers screened and reviewed all identified articles.RESULTS One hundred and sixty two citations were initially retrieved with 18 studies included in this systematic review. The majority of included studies were from Brazil(n =13, 72%). The incidence of UC ranged from 4.3-5.3/100000 personyears whilst the incidence of CD ranged from 0.74-3.5/100000 person-years.Prevalence ranged from 15.0-24.1/100000 inhabitants for UC and from 2.4-14.1/100000 inhabitants for CD. The incidence and prevalence of both UC and CD has increased significantly in Brazil over the past 21 years. Pancolitis was the most common disease distribution in patients with UC whilst colonic involvement was the most common distribution in CD. People residing in urbanareas were at higher risk of developing both CD and UC.CONCLUSION The IBD burden in South America is increasing at a rate possibly even greater than other developing regions around the world. There is a paucity of highquality epidemiological studies and further robust and representative data are required to further explore modifiable risk factors and disease phenotypes.     

The association between the gut microbiota and the inflammatory bowel disease activity: a systematic review and meta-analysis

Background: The pathogenesis of inflammatory bowel diseases (IBD) involves complex interactions between the microbiome and the immune system. We evaluated the association between the gut microbiota and disease activity in IBD patients.

Methods: Systematic review of clinical studies based on a published protocol. Included patients had ulcerative colitis (UC) or Crohn’s disease (CD) classified as active or in remission. We selected bacteria assessed in at least three studies identified through electronic and manual searches (November 2015). Bias control was evaluated with the Newcastle Ottawa scale (NOS). Results of random-effects meta-analyses were presented as mean differences (MD).

Results: Three prospective and seven cross-sectional studies (NOS score 6–8) were included. Five studies included patients with CD (231 patients) and eight included patients with UC (392 patients). Compared to patients in remission, patients with active IBD had lower abundance of Clostridium coccoides (MD?=??0.49, 95% CI: ?0.79 to ?0.19), Clostridium leptum (MD?=??0.44, 95% CI: ?0.74 to ?0.14), Faecalibacterium prausnitzii (MD?=??0.81, 95% CI: ?1.23 to ?0.39) and Bifidobacterium (MD?=??0.37, 95% CI: ?0.56 to ?0.17). Subgroup analyses showed a difference in all four bacteria between patients with UC classified as active or in remission. Patients with active CD had fewer C. leptum, F. prausnitzii and Bifidobacterium, but not C. coccoides.

Conclusion: This systematic review suggests that dysbiosis may be involved in the activity of IBD and that there may be differences between patients with CD and UC.     

Dual biological therapy with anti-TNF,vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy.

Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety.

Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted.

Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn’s disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported.

Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.     

Biosimilars in paediatric inflammatory bowel disease

The introduction of biological treatments has changed disease outcomes for patients with inflammatory bowel disease. Biologicals have high efficacy, and can induce and maintain remission after failed responses to conventional immunosuppressive and/or steroid therapy. The increasing occurrence of severe disease at diagnosis has resulted in infliximab being more often introduced as the firstline treatment in a "top-down" approach. Besides their favourable efficacy and safety profile, biologicals have one significant disadvantage, which is their high cost. This results in many patients stopping therapy prematurely, with the maintenance phase being too short. This often leads to disease exacerbation shortly after treatment cessation. Every newly started course of biological therapy can induce production of anti-drug antibodies, which can result in treatment failure and possible allergic/anaphylactic reactions. The introduction of biological biosimilars was intended to greatly reduce therapy costs thus increasing the availability of these agents to more patients. It was also anticipated that biosimilars would prevent premature termination of therapy. Analyses of paediatric data suggest that biosimilar infliximabs are equally effective as the reference infliximab. Safety patterns also seem to be similar. Paediatric experience places costtherapy reductions at around 10%-30%.     

Minimum sample size estimates for trials in inflammatory bowel disease: A systematic review of a support resource

BACKGROUNDOf 25% of randomised controlled trials (RCTs) on interventions for inflammatory bowel disease (IBD) have no power calculation. AIMTo systematically review RCTs reporting interventions for the management of IBD and to produce data for minimum sample sizes that would achieve appropriate power using the actual clinical data.METHODSWe included RCTs retrieved from Cochrane IBD specialised Trial register and CENTRAL investigating any form of therapy for either induction or maintenance of remission against control, placebo, or no intervention of IBD in patients of any age. The relevant data was extracted, and the studies were grouped according to the intervention used. We recalculated sample size and the achieved difference, as well as minimum sample sizes needed in the future.RESULTSA total of 105 trials were included. There was a large discrepancy between the estimated figure for the minimal clinically important difference used for the calculations (15% group differences observed vs 30% used for calculation) explaining substantial actual sample size deficits. The minimum sample sizes indicated for future trials based on the 25 years of trial data were calculated and grouped by the intervention. CONCLUSIONA third of intervention studies in IBD within the last 25 years are underpowered, with large variations in the calculation of sample sizes. The authors present a sample size estimate resource constructed on the published evidence base for future researchers and key stakeholders within the IBD trial field.     

Obesity and novel management of inflammatory bowel disease

Obesity is prevalent within the inflammatory bowel disease(IBD) population,particularly in newly developed countries.Several epidemiological studies have suggested that 15%-40% of IBD patients are obese,and there is a potential role of obesity in the pathogenesis of IBD.The dysfunction of mesenteric fat worsens the inflammatory course of Crohn’s disease and may induce formation of strictures or fistulas.Furthermore,obesity may affect the disease course or treatment response of IBD.Given the incr...     

炎症性肠病相关性肝病的研究进展

炎症性肠病(inflammatory bowel disease,IBD)是一种累及回肠、结肠、直肠的特发性炎症性疾病,本病主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。除常见的消化道症状外,研究发现IBD合并肝脏疾病较为常见,是IBD常见的肠外表现之一,其严重影响IBD的预后与转归。本文就IBD相关性肝病的分类和总结作一概述,以期为IBD及其肝脏病变的临床诊疗提供参考。     

Secondary causes of inflammatory bowel diseases

Inflammatory bowel diseases(IBD), conventionally consist of Crohn's disease(CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.     

Declining use of combination infliximab and immunomodulator for inflammatory bowel disease in the community setting

AIM To describe trends of combination therapy (CT) of infliximab (IFX) and immunomodulator (IMM) for inflammatory bowel disease(IBD) in the community setting. METHODS A retrospective study was conducted of all IBD patients referred for IFX infusion to our community infusion center between 04/01/01 and 12/31/14. CT was defined as use of IFX with either azathioprine, 6-mercaptopurine, or methotrexate. We analyzed trends of CT usage overall, for Crohn's disease (CD) and ulcerative colitis (UC), and for the subgroups of induction patients. We also analyzed the trends of CT use in these groups over the study period, and compared the rates of CT use prior to and after publication of the landmark SONIC trial.RESULTS Of 258 IBD patients identified during the 12 year study period, 60 (23.3%) received CT, including 35 of 133(26.3%) induction patients. Based on the CochranArmitage trend test, we observed decreasing CT use for IBD patients overall(P 0.0001) and IBD induction patients,(P = 0.0024). Of 154 CD patients, 37(24.68%) had CT, including 20 of 77 (26%) induction patients.The Cochran Armitage test showed a trend towards decreasing CT use for CD overall(P 0.0001) and CD induction,(P = 0.0024). Overall, 43.8% of CD patients received CT pre-SONIC vs 7.4% post-SONIC (P 0.0001). For CD induction, 40.0% received CT preSONIC vs 10.8% post-SONIC(P = 0.0035). Among the 93 patients with UC, 19 (20.4%) received CT. Of 50 induction patients, 14 (28.0%) received CT. The trend test of the 49 patients with a known year of induction again failed to demonstrate any significant trends in the use of CT(P = 0.6). CONCLUSION We observed a trend away from CT use in IBD. A disconnect appears to exist between expert opinion and evidence favoring CT with IFX and IMM, and evolving community practice.     

A systematic review and meta-analysis of anti-adhesion molecule therapy in patients with active Crohn's disease

Abstract

Objective. Due to the crucial role played by adhesion molecules in the pathogenesis of Crohn’s disease (CD), targeting of these molecules has recently been proposed as a new direction for the development of anti-inflammatory strategies for CD. The aim of this study was to provide up-to-date evidence on the effectiveness and safety of anti-adhesion molecule therapy in treating active CD. Material and methods. We studied articles retrieved by PubMed, EMBASE, the Cochrane Library and the Science Citation Index for randomized controlled trials (RCTs) relevant to CD and anti-adhesion molecule therapy. Results. Seven RCTs comparing anti-adhesion molecule therapy with placebo were included in a meta-analysis to evaluate the efficacy and safety of anti-adhesion molecule strategies in active CD. On the basis of pooled results of the seven RCTs (n = 2228), we found a significant difference in clinical remission rates between groups [relative risk (RR) 1.31, 95% confidence interval (CI) 1.12–1.52, fixed-effect model]. Five RCTs (n = 2178) compared the response rates of anti-adhesion molecule therapy and placebo; in overall analysis, anti-adhesion molecule therapy was effective for active CD (RR 1.28, 95% CI 1.16–1.42, random-effect model). In five studies enrolling 1867 individuals, anti-adhesion molecule therapy did not increase adverse events (RR 1.03, 95% CI 0.98–1.08, fixed-effect model). Conclusions. Anti-adhesion molecule therapy, which could prevent leukocyte recruitment, was effective and safe for treating active CD. Because of the small number of studies included in this meta-analysis, the results should be interpreted with caution.     

Systematic review of nutrition screening and assessment in inflammatory bowel disease

BACKGROUND Malnutrition is prevalent in inflammatory bowel disease (IBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with IBD remains unclear. AIM To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with IBD. METHODS Comprehensive searches performed in Medline, CINAHL Plus and PubMed. Included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in IBD. Excluded: Review articles/case studies;use of body mass index/laboratory values as sole NST/NAT;age<16. RESULTS Of 16 studies and 1618 patients were included, 72% Crohn’s disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition Inflammation Risk Tool (MIRT), Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MIRT, NRS-2002 and Nutritional Risk Index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSION There is limited evidence correlating NSTs, NATs and clinical outcomes in IBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MIRT, represent key, clinically-relevant areas for future exploration.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

Updates in therapeutic drug monitoring in inflammatory bowel disease

Biologics and immunomodulators (IMM) are generally considered the most effective therapies for the treatment of ulcerative colitis and Crohn’s disease. However, despite the efficacy of these therapies, many patients either have a primary lack of response or a secondary loss of response to these medications. Therapeutic drug monitoring (TDM) is a systematic approach to managing such patients. In this review, we summarize the latest data on TDM, including reactive and proactive TDM, in patients with inflammatory bowel disease on biologics and/or IMM.     

Cytomegalovirus in inflammatory bowel disease: A systematic review

AIM: To identify definitions of cytomegalovirus(CMV) infection and intestinal disease, in inflammatory bowel disease(IBD), to determine the prevalence associated with these definitions.METHODS: We conducted a systematic review and interrogated Pub Med, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both Me SH-terms and free searches were performed. We included all types of English-language(clinical) trials concerning diagnostics and prevalence of CMV in IBD.RESULTS: The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia.CONCLUSION: We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials.     

Anemia at the time of diagnosis of inflammatory bowel disease: Prevalence and associated factors in adolescent and adult patients

BackgroundThe prevalence, characteristic and determinants of anemia, at the time of inflammatory bowel disease (IBD) diagnosis have yet to be fully elucidated.MethodsRetrospective cross-sectional study. Analytical data and disease characteristics obtained upon diagnosis of 1278 IBD patients [Crohn’s disease/ulcerative colitis (CD/UC): 718/560] were collected.ResultsAnemia was present in 41.2% of patients at diagnosis (47% and 33.8% of CD and UC patients, respectively; p < 0.001), being severe in 5.5%. Iron deficiency anemia represented 69.6% of cases, with no differences between CD and UC. Female sex was the strongest risk factor for anemia in both CD and UC (OR 7.11; 95%CI 4.18–12.10 and 6.55; 95%CI 3.39–12.63, respectively), followed by elevated (≥2 mg/dL) C-reactive protein (OR 4.08; 95%CI 2.39–6.97 and 4.58; 95%CI 2.26–9.27, respectively). Current smoking was a risk factor for anemia in CD (OR 2.23; 95%CI 1.24–4.02), but a protective one in UC (OR 0.36; 95%CI 0.14–0.92). A penetrating CD behavior increased the risk of anemia (OR 3.34; 95%CI 1.36–8.21); in UC, anemia increased with disease extension (E2 + E3) (OR 1.80; 95%CI 1.13–2.86).ConclusionsFemale sex and disease activity are major determinants of anemia at IBD diagnosis. Anemia is associated with disease behavior in CD and with disease extension in UC.     

Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: The IBSEN study

Objective: Fatigue is a major concern for patients with ulcerative colitis (UC) and Crohn’s disease (CD), but evidence from population-based studies regarding fatigue in long-standing inflammatory bowel disease (IBD) patients is scarce. Our aims were to assess fatigue scores and the prevalence of chronic fatigue in IBD patients 20 years after diagnosis and to identify variables associated with fatigue in this cohort.

Methods: Twenty years after diagnosis, patients from a cohort with incident IBD were invited to a follow-up visit that included a structured interview, a clinical examination, laboratory tests and the Fatigue Questionnaire (FQ). Fatigue scores were obtained, and factors associated with fatigue were assessed via linear and logistic regression analyses.

Results: Of the 599 invited patients, 440 (73.5%) completed the FQ. Among those with active disease, we found significantly higher fatigue scores than among those with quiescent disease (fatigue scores: UC 17.1 versus 12.4, p?<?.001, and CD 17.5 versus 13.3, p?<?.001). The fatigue scores of those with quiescent disease were comparable with those of the reference population. Chronic fatigue was more frequent among IBD patients than in the reference population. Factors associated with fatigue included self-perceived disease activity, poor sleep quality, anxiety and depression.

Conclusion: At 20 years after IBD diagnosis, fatigue scores were higher and chronic fatigue was more frequent among IBD patients with active disease than in the reference population and among those with quiescent IBD. Subjectively perceived disease activity, sleep quality, anxiety and depression were associated with fatigue in IBD patients.