New serological markers in pediatric patients with inflammatory bowel disease

The spectrum of serological markers associated with inflammatory bowel disease(IBD)is rapidly growing.Due to frequently delayed or missed diagnoses,the application of non-invasive diagnostic tests for IBD,as well as differentiation between ulcerative colitis(UC)and Crohn’s disease(CD),would be useful in the pediatric population.In addition,the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody(pANCA)improved the sensitivity of serological markers in pediatric patients with CD and UC.Some studies suggested that age-associated differences in the patterns of antibodies may be present,particularly in the youngest children.In CD,most patients develop stricturing or perforating complications,and a significant numberof patients undergo surgery during the disease course.Based on recent knowledge,serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery.Pediatric UC is characterized by extensive colitis and a high rate of colectomy.In patients with UC,high levels of antiCBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis.Thus,serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression.In conclusion,identification of patients at an increased risk of rapid disease progression is of great interest,as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD,and reduce complications and hospitalizations.     

Crucial steps in the natural history of inflammatory bowel disease

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, progressive and disabling disorders. Over the last few decades, new therapeutic approaches have been introduced which have led not only to a reduction in the mortality rate but also offered the possibility of a favorable modification in the natural history of IBD. The identification of clinical, genetic and serological prognostic factors has permitted a better stratification of the disease, thus allowing the opportunity to indicate the most appropriate therapy. Early treatment with immunosuppressive drugs and biologics has offered the opportunity to change, at least in the short term, the course of the disease by reducing, in a subset of patients with IBD, hospitalization and the need for surgery. In this review, the crucial steps in the natural history of both UC and CD will be discussed, as well as the factors that may change their clinical course. The methodological requirements for high quality studies on the course and prognosis of IBD, the true impact of environmental and dietary factors on the clinical course of IBD, the clinical, serological and genetic predictors of the IBD course (in particular, which of these are relevant and appropriate for use in clinical practice), the impact of the various forms of medical treatment on the IBD complication rate, the role of surgery for IBD in the biologic era, the true magnitude of risk of colorectal cancer associated with IBD, as well as the mortality rate related to IBD will be stressed; all topics that are extensively discussed in separate reviews included in this issue of World Journal of Gastroenterology.     

Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility

Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),represents a group of chronic inflammatory disorders caused by dysregulated immune responses in genetically predisposed individuals.Genetic markers are associated with disease phenotype and long-term evolution,but their value in everyday clinical practice is limited at the moment.IBD has a clear immunological background and interleukins play key role in the process.Almost130 original papers were revised including meta-analysis.It is clear these data are very important for understanding the base of the disease,especially in terms of clinical utility and validity,but text often do not available for the doctors use these in the clinical practice nowadays.We conducted a systematic review of the current literature on interleukin and interleukin receptor gene polymorphisms associated with IBD,performing an electronic search of PubMed Database from publications of the last 10 years,and used the following medical subject heading terms and/or text words:IBD,CD,UC,interleukins and polymorphisms.     

Indeterminate colitis: a significant subgroup of pediatric IBD

BACKGROUND: Indeterminate colitis (IC) is a subgroup of inflammatory bowel disease (IBD) that cannot be characterized as either ulcerative colitis (UC) or Crohn's disease (CD). Our aims are to determine the prevalence of IC in our pediatric patient population and to describe its clinical presentation, natural history,and disease distribution. METHODS: We performed a retrospective database analysis of all children diagnosed with IBD at the Johns Hopkins Children's IBD Center between 1996 and 2001. Patient demographics, including age, sex, and age at disease onset, were tallied. Disease distribution was identified on the basis of a review of all endoscopic, colonoscopic, histopathological, and radiological records. All of the patients were followed up clinically to determine the extent of disease progression on the basis of the initial diagnosis of IC. RESULTS: Among 250 children registered in the database, 127 (50.8%) had a diagnosis of CD, 49 (19.6%) had UC, and 74(29.6%) had IC. Patients with IC had a significantly younger mean +/- SEM age (9.53 +/- 4.8 years) at diagnosis compared with patients with CD (12.4 +/- 3.8 years; P < 0.001) but not compared with patients with UC (7.41 +/- 3.5 years). Among the patients with IC, 59 (79.7%) had a pancolitis at diagnosis, and the remaining 15 had left-sided disease that progressed to a pancolitis within a mean of 6 years. Twenty-five patients (33.7%) with an initial diagnosis of IC were reclassified to either CD or UC after a median follow-up of 1.9 years (range 0.6-4.5 years). Forty-nine patients (66.2%) maintained their diagnosis of IC after a mean follow-up of 7 years (SEM 2.5 years). CONCLUSIONS: IC is a distinct pediatric subgroup of IBD with a prevalence that is higher than that observed in adults. Children with IC have an early age of disease onset and a disease that rapidly progresses to pancolitis. Longitudinal studies are needed to determine the clinical implications of this pediatric IBD subgroup.     

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

Inflammatory bowel diseases(IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease(CD) and ulcerative colitis(UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria(microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroidfree long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered(oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease(CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems(Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8~+ T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.     

Arterial Stiffness in Inflammatory Bowel Disease: An Updated Systematic Review and Meta-Analysis

BackgroundThis systematic review and meta-analysis were carried out on well-conducted and adequately powered studies to explore whether arterial stiffness was associated with inflammatory bowel disease (IBD).MethodsThe search for potential literature was conducted on PubMed, MEDLINE, Cochrane Library, and Embase from inception to February 15, 2020. The studies assessing arterial stiffness in IBD were reviewed and included.ResultsConclusively, 17 eligible trials with a total of 2188 participants were in compliance with the inclusion criteria. Of the included 2188 participants, the cases for ulcerative colitis (UC) and Crohn’s disease (CD) were 558 and 693, respectively. Altogether 10 studies were conducted to evaluate the carotid-femoral pulse wave velocity (CPWV) in overall IBD patients, which was significantly increased with the mean difference (MD) and 95% CI as 0.70 (0.48-0.92, P < .01). The pooled results for CPWV in patients with CD and UC were also faster than that of control groups with MD and 95% CI as 1.09 (0.45-1.72) and 0.57 (0.57-1.24), respectively. The CPWV in CD and UC groups was comparable with a MD of 0.07 (P = .74, 95% CI: −0.32 to 0.45).ConclusionArterial stiffness had associations with the overall IBD, UC, and CD with a similar strength of association between UC and CD.     

Colorectal cancer in patients with inflammatory bowel disease:Can we predict risk?

The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), may be complicated by colorectal cancer (CRC). In a recent population-based cohort study of 47 347 Danish patients with IBD by Tine Jess and colleagues 268 patients with UC and 70 patients with CD developed CRC during 30 years of observation. The overall risk of CRC among patients with UC and CD was comparable with that of the general population. However, patients diagnosed with UC during childhood or as adolescents, patients with long duration of disease and those with concomitant primary sclerosing cholangitis were at increased risk. In this commentary, we discuss the mechanisms underlying carcinogenesis in IBD and current investigations of genetic susceptibility in IBD patients. Further advances will depend on the cooperative work by epidemiologist and molecular geneticists in order to identify genetic polymorphisms involved in IBD-associated CRC. The ultimate goal is to incorporate genotypes and clinical parameters into a predictive model that will refine the prediction of risk for CRC in colonic IBD. The challenge will be to translate these new findings into clinical practice and to determine appropriate preventive strategies in order to avoid CRC in IBD patients. The achieved knowledge may also be relevant for other inflammation-associated cancers.     

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.     

Epidemiology of fibrostenosing inflammatory bowel disease

Fibrostenosis occurs in both Crohn's disease (CD) and ulcerative colitis (UC). Up to 21% of patients with CD present with strictures at diagnosis, while the rate of stenosis varies from 1% to 11% in UC. Despite the increasing use of immunomodulators and biologics in treatment, there has been no decrease in the rate of progression from inflammatory to complicated disease phenotypes (either stricturing or penetrating). The presence of stenosis is an independent risk factor for surgery in patients with CD, who are at a risk of postoperative recurrence at a rate of up to 55% at 10 years after surgery. Patients with inflammatory bowel disease (IBD) strictures are at risk of malignant transformation. Thus, surveillance colonoscopy should be offered to this group of patients. Several risk factors for the development of stricture have been identified. In CD, patients aged less than 40‐years old, with perianal disease at diagnosis, who need steroids at the first flare up or have ileal disease are at the risk of developing strictures; while in UC, patients with extensive colitis and long‐standing disease are at risk. Recently, microbiota signatures have also been identified as markers for stricture development. The presence of Ruminococcus spp. is associated with the development of stricture in pediatric patients with CD. In this review, we highlight the epidemiology, risk factors and natural history of fibrostenosing IBD.     

炎症性肠病患者血浆差异蛋白质的筛选

目的 应用表面增强激光解析电离飞行质谱技术(SELDI-TOF-MS)寻找溃疡性结肠炎(UC)和克罗恩病(CD)患者的血浆差异表达蛋白,建立筛选模型.方法 采用CM10芯片对24例UC、25例CD和25例正常对照者血浆进行分析,从蛋白表达图谱中发现差异蛋白,建立区分CD和正常对照、UC和正常对照、UC和CD以及炎症性肠病(IBD)和正常对照的决策树分析模型,并进行盲法筛选.结果 在质荷比(m/z)2000～30 000范围内,CD和正常对照之间、UC和正常对照之间、IBD和正常对照之间具有2倍以上差异的蛋白峰数分别为9个、5个和11个(P＜0.05),软件自动选取m/z为8208、8837的蛋白质建立区分CD和正常对照的决策树模型,m/z为6985的蛋白质建立区分UC和正常对照的决策树模型,m/z为8208、1752、28 840和1702的4个蛋白质建立IBD和正常对照的决策树模型,3个决策树模型的灵敏度分别为96%、82%、91%,特异度分别为100%、85%、100%.结论 m/z 8208对于CD筛选价值高,特异度好,值得进一步探索.     

Primary sclerosing cholangitis associated colitis: Characterization of clinical,histologic features,and their associations with liver transplantation

BACKGROUND Primary sclerosing cholangitis(PSC) associated inflammatory bowel disease(IBD) is a unique form of IBD(PSC-IBD) with distinct clinical and histologic features from ulcerative colitis(UC) and Crohn disease(CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n = 28), CD(n = 10), PSC and UC(PSC-UC; n = 26); PSC and CD(PSC-CD; n = 6); and PSC and no IBD(PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation(OLT) were noted.RESULTSPSC-UC patients had more isolated right-sided disease(P = 0.03), and less active inflammation in left colon, rectum(P = 0.03 and P = 0.0006), and overall(P = 0.0005) compared to UC. They required less steroids(P = 0.01) and fewer colectomies(P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC(P = 0.1). PSC-IBD(PSC-UC and PSCCD) patients with OLT had severe disease in the left colon and rectum(P = 0.04).CONCLUSION PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.     

Lack of correlation between Treg quantification assays in inflammatory bowel disease patients

AIM:To compare the number of regulatory T-cells( Tregs) measured by flow cytometry with those obtained using a real-time quantitative PCR(q PCR) method in patients suffering from inflammatory bowel disease(IBD).METHODS:Tregs percentages obtained by both flow cytometry and q PCR methods in 35 adult IBD patients,18 out of them with Crohn′s disease(CD)and 17 with ulcerative colitis(UC)were compared to each other as well as to scores on two IBD activity questionnaires using the Harvey Bradshaw Index(HBI)for CD patients and the Simple Colitis Clinical Activity Index(SCCAI)for UC patients.The Treg percentages by flow cytometry were defined as CD4+CD25highCD127lowFOXP3+cells in peripheral blood mononuclear cells,whereas the Treg percentages by q PCR method were determined as FOXP3 promoter demethylation in genomic DNA.RESULTS:We found an average of 1.56%±0.78%Tregs by using flow cytometry,compared to 1.07%±0.53%Tregs by using q PCR in adult IBD patients.There were no significant correlations between either the percentages of Tregs measured by flow cytometry or q PCR and the HBI or SCCAI questionnaire scores in CD or UC patients,respectively.In addition,there was no correlation between Treg percentages measured by q PCR and those measured by flow cytometry(r=-0.06,P=0.73;Spearman Rho).These data suggest that,either Treg-related immune function or the clinical scores in these IBD patients did not accurately reflect actual disease activity.Until the cause(s)for these differences are more clearly defined,the resultssuggest caution in interpreting studies of Tregs in various inflammatory disorders.CONCLUSION:The two methods did not produce equivalent measures of the percentage of total Tregs in the IBD patients studied which is consistent with the conclusion that Tregs subtypes are not equally detected by these two assays.     

Serological profiling of Crohn’s disease and ulcerative colitis patients reveals anti-microbial antibody signatures

BACKGROUNDThe healthcare burden of inflammatory bowel disease (IBD) is rising globally and there are limited non-invasive biomarkers for accurate and early diagnosis. AIMTo understand the important role that intestinal microbiota play in IBD pathogenesis and identify anti-microbial antibody signatures that benefit clinical management of IBD patients.METHODSWe performed serological profiling of 100 Crohn’s disease (CD) patients, 100 ulcerative colitis (UC) patients and 100 healthy controls against 1173 bacterial and 397 viral proteins from 50 bacteria and 33 viruses on protein microarrays. The study subjects were randomly divided into discovery (n = 150) and validation (n = 150) sets. Statistical analysis was performed using R packages. RESULTSAnti-bacterial antibody responses showed greater differential prevalence among the three subject groups than anti-viral antibody responses. We identified novel antibodies against the antigens of Bacteroidetes vulgatus (BVU_0562) and Streptococcus pneumoniae (SP_1992) showing higher prevalence in CD patients relative to healthy controls. We also identified antibodies against the antigen of Streptococcus pyogenes (SPy_2009) showing higher prevalence in healthy controls relative to UC patients. Using these novel antibodies, we built biomarker panels with area under the curve (AUC) of 0.81, 0.87, and 0.82 distinguishing CD vs control, UC vs control, and CD vs UC, respectively. Subgroup analysis revealed that penetrating CD behavior, colonic CD location, CD patients with a history of surgery, and extensive UC exhibited highest antibody prevalence among all patients. We demonstrated that autoantibodies and anti-microbial antibodies in CD patients had minimal correlation.CONCLUSIONWe have identified antibody signatures for CD and UC using a comprehensive analysis of anti-microbial antibody response in IBD. These antibodies and the source microorganisms of their target antigens improve our understanding of the role of specific microorganisms in IBD pathogenesis and, after future validation, should aid early and accurate diagnosis of IBD.     

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies in patients with inflammatory bowel disease

Atypical, cytoplasmic and perinuclear anti-neutrophil cytoplasmic antibodies (x-, c- and pANCA, respectively) are associated with a variety of inflammatory diseases, including inflammatory bowel disease (IBD). Anti-neutrophil cytoplasmic antibodies are more common in patients with ulcerative colitis (UC) than in patients with Crohn's disease (CD). Most publications only refer to p- and cANCA in relation to IBD. We have prospectively evaluated the reactivity of sera from 58 patients with IBD and 10 healthy controls against human neutrophils with emphasis on the distinction of the ANCA types. The sera were incubated with ethanol- and formaldehyde-fixed granulocytes to differentiate between c-, p- and xANCA. The results showed that 10 of 24 patients with UC were positive for ANCA, whereas only one of 34 patients with CD was ANCA positive. These results correspond to a sensitivity of 42%, a specificity of 97%, a negative predictive value of 91% and a positive predictive value of 75% in UC. Of the 11 ANCA-positive sera, two showed a cytoplasmic staining pattern, three showed a perinuclear and six an atypical staining pattern. The disease activity was not correlated to either the ANCA titre or to the presence of ANCA in the serum. In conclusion, ANCA are of limited value in differentiating between UC and CD. Because the majority of ANCA in patients with IBD are xANCA, these ANCA should be explored by not only incubating on ethanol-fixed granulocytes, but also on formaldehyde-fixed granulocytes.     

Dynamic immunoglobulin responses to gut bacteria during inflammatory bowel disease

ABSTRACT

Aberrant immune responses against gut microbiota are thought to be key drivers of inflammatory bowel disease (IBD) pathogenesis. However, the extent and targets of immunoglobulin (Ig) A versus IgG responses to gut bacteria in IBD and its association with IBD severity is not well understood. Here, we address this by analyzing fecal samples from Crohn’s disease (CD), ulcerative colitis (UC), and Non-IBD patients by flow cytometry for the frequency of bacteria that were endogenously bound with IgA and/or IgG. Assessment of IBD patients from two geographically distinct cohorts revealed increased percentages of IgA- and IgG-bound fecal bacteria compared to non-IBD controls. Notably, the two major subsets of IBD showed distinct patterns of Ig-bound bacteria, with CD activity associated with increases in both IgA and IgG-bound bacteria, whereas UC activity correlated only with increases in IgG-bound bacteria. Analysis of the flow sorted Ig-bound bacterial repertoire by 16S rDNA sequencing revealed taxa that were Ig-bound specifically in IBD. Notably, this included bacteria that are also thought to reside in the oral pharynx, including Gemella, Peptostreptococcus, and Streptococcus species. These data show that the pattern of IgA and IgG binding to fecal bacteria is distinct in UC and CD. In addition, the frequency of Ig-bound fecal bacteria may have potential as a non-invasive biomarker for disease activity. Finally, our results support the hypothesis that immune responses to oral pharyngeal bacteria may play an important role in the pathogenesis of IBD.     

Upper gastrointestinal tract involvement of pediatric inflammatory bowel disease: A pathological review

Upper gastrointestinal(UGI) tract involvement of inflammatory bowel disease(IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis(UC), atypical UC, Crohn's disease(CD) and IBD unclassified.Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid(non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD,is histologically characterized by increased intraepithelial lymphocytes(> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis,villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.     

Similar clinical characteristics of familial and sporadic inflammatory bowel disease in South Korea

AIM:To investigate differences of clinical characteristics and disease courses between familial and sporadic inflammatory bowel disease(IBD)patients.METHODS:We obtained clinical data on Crohn’s disease(CD)(n=691)and ulcerative colitis(n=1113)from a tertiary referral medical center between 2005and 2012.Seventeen patients(2.5%)with CD and27 patients(2.4%)with ulcerative colitis(UC)were identified as having a familial history of IBD,including the first and second degree relatives.For each control case,three times the number of age-,sex-,and diagnosis year-matched CD and UC patients,without a family history of IBD,were randomly selected in this case control study.RESULTS:There were no significant differences in age or main symptom at diagnosis,extraintestinal manifestation,location/extent,behavior of disease activity,number of hospitalizations,number of operations,operation type,number of relapses,or oral medical treatment between familial and sporadic CD and UC patients.Median(min-max)follow-up periods after diagnosis of familial CD and sporadic CD patients were 84(24-312)and 36(8-240)mo,respectively(P=0.008).Familial CD patients more frequently used anti-tumor necrosis factor(TNF)antibodies compared to sporadic CD patients(17.6%vs 0%,P=0.014).CONCLUSION:In conclusion,a family history of IBD does not seem to be an important predictive factor affecting clinical characteristics or disease course even if there is a more frequent use of anti-TNF antibodies in familial CD patients compared to sporadic CD patients.