Inflammatory bowel disease increases the risk of hepatobiliary pancreatic cancer: A two-sample Mendelian randomization analysis of European and East Asian populations.

BACKGROUND: Both inflammatory bowel disease (IBD) and hepato-pancreato-biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. METHODS: Herein, we utilized inverse-variance weighting to conduct a two-sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. RESULTS: Compared to the general population, IBD patients in Europe exhibited a 1.22-fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022-1.4888 (p = 0.0475). We also found a 1.14-fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017-1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28-fold higher (95% CI = 1.0709-1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12-fold (95% CI: 1.1466-1.3334, p < 0.0001) and 1.31-fold (95% CI: 1.0983-1.5641, p = 0.0027) increased incidences of HCC and cholangiocarcinoma (CCA), respectively. Finally, the incidence of PC was 1.19-fold higher in CD patients than in the general population (95% CI = 1.0741-1.3132, p = 0.0008). CONCLUSION: Our study validated that IBD is a risk factor for HPBC. This causal relationship exhibited significant heterogeneity in different European and East Asian populations.

Predictors of Immunogenicity to Infliximab among Patients with Inflammatory Bowel Disease: Does Ethnicity Matter?

BACKGROUND: Up to 60% of inflammatory bowel disease (IBD) patients treated with infliximab develop antibodies to infliximab (ATI), which are associated with low drug levels and loss of response (LOR). Hence, mapping out predictors of immunogenicity toward infliximab is essential for tailoring patient-specific therapy. Jewish Sephardi ethnicity, in addition to monotherapy, has been previously identified as a potential risk factor for ATI formation and infliximab failure. OBJECTIVES: To explore the association between Jewish sub-group ethnicity among patients with IBD and the risk of infliximab immunogenicity and therapy failure. To confirm findings of a previous cohort that addressed the same question. METHODS: This retrospective cohort study included all infliximab-treated patients of Jewish ethnicity with regular prospective measurements of infliximab trough levels and ATI. Drug and ATI levels were prospectively measured, clinical data was retrieved from medical charts. RESULTS: The study comprised 109 Jewish patients (54 Ashkenazi, 55 Sephardi) treated with infliximab. There was no statistically significant difference in proportion of ATI between Sephardi and Ashkenazi patients with IBD (32% Ashkenazi and 33% Sephardi patients developed ATI, odds ratio [OR] 0.944, P = 0.9). Of all variables explored, monotherapy and older age were the only factors associated with ATI formation (OR 0.336, 95% confidence interval 0.145-0.778, P = 0.01, median 34 vs. 28, interquartile range 28-48, 23-35 years, P = 0.02, respectively). CONCLUSIONS: Contrary to previous findings, Sephardi Jewish ethnicity was not identified as a risk factor for ATI formation compared with Ashkenazi Jewish ethnicity. Other risk factors remained unchanged.

Prevalence of Inflammatory Bowel Disease Among Medicare Fee-For-Service Beneficiaries - United States, 2001-2018.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. The number of affected persons worldwide has increased from 3.7 million in 1990 to 6.8 million in 2017 (1). The disease is more prevalent among non-Hispanic White persons than it is among persons in other racial/ethnic groups (2). As the prevalence increases with age group (2), it is important to understand the disease epidemiology among the older population. CDC analyzed 2018 Medicare data among beneficiaries aged ≥67 years to examine differences by demographic characteristics for both diseases and to assess trends of prevalence from 2001 through 2018 both overall and by race and ethnicity. In 2018, 0.40% and 0.64% of 25.1 million Medicare fee-for-service beneficiaries aged ≥67 years had received a diagnosis of either Crohn's disease or ulcerative colitis. Prevalence varied by age, sex, race and ethnicity, urban-rural residency, and state. During 2001-2018, the age-adjusted prevalence of both diseases increased (Crohn's disease annual percentage change [APC] = 3.4%, ulcerative colitis APC = 2.8%). The increase was higher among non-Hispanic Black persons (Crohn's disease APC = 5.0%, ulcerative colitis APC = 3.5%) than it was among non-Hispanic White, Hispanic, and Asian/Pacific Islander (A/PI) persons. Prevalence was consistently highest among non-Hispanic White persons for both diseases and lowest among A/PI persons for Crohn's disease. The study findings of increasing prevalence in all racial/ethnic groups among older adults, especially the higher rate of increase among certain racial/ethnic minority groups, underscore the importance for promoting health equity, guiding efforts to tailor disease management strategies for different populations, and continuing to monitor the temporal trends of the disease.

Identification of Three Novel Susceptibility Loci for Inflammatory Bowel Disease in Koreans in an Extended Genome-Wide Association Study.

BACKGROUND AND AIMS: Genome-wide association studies [GWAS] of inflammatory bowel disease [IBD] in multiple populations have identified over 240 susceptibility loci. We previously performed a largest-to-date Asian-specific IBD GWAS to identify two new IBD risk loci and confirm associations with 28 established loci. To identify additional susceptibility loci in Asians, we expanded our previous study design by doubling the case size with an additional dataset of 1726 cases and 378 controls. METHODS: An inverse-variance fixed-effects meta-analysis was performed between the previous and the new GWAS dataset, comprising a total of 3195 cases and 4419 controls, followed by replication in an additional 1088 cases and 845 controls. RESULTS: The meta-analysis of Korean GWAS identified one novel locus for ulcerative colitis at rs76227733 on 10q24 [pcombined = 6.56 × 10-9] and two novel loci for Crohn's disease [CD] at rs2240751 on 19p13 [pcombined = 3.03 × 10-8] and rs6936629 on 6q22 [pcombined = 3.63 × 10-8]. Pathway-based analysis of GWAS data using MAGMA showed that the MHC and antigenic stimulus-related pathways were more significant in Korean CD, whereas cytokine and transcription factor-related pathways were more significant in European CD. Phenotype variance explained by the polygenic risk scores derived from Korean data explained up to 14% of the variance of CD whereas those derived from European data explained 10%, emphasizing the need for large-scale genetic studies in this population. CONCLUSIONS: The identification of novel loci not previously associated with IBD suggests the importance of studying IBD genetics in diverse populations.

Ethnic Differences in the Smoking-related Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: The association between smoking and inflammatory bowel disease [IBD] relies on old meta-analyses including exclusively non-Jewish White populations. Uncertainty persists regarding the role of smoking in other ethnicities. METHODS: We systematically searched Medline/PubMed, Embase, and Scopus for studies examining tobacco smoking and the risk of developing IBD, ie, Crohn's disease [CD] or ulcerative colitis [UC]. Two authors independently extracted study data and assessed each study's risk of bias. We examined heterogeneity and small-study effect, and calculated summary estimates using random-effects models. Stratified analyses and meta-regression were employed to study the association between study-level characteristics and effect estimates. The strength of epidemiological evidence was assessed through prespecified criteria. RESULTS: We synthesised 57 studies examining the smoking-related risk of developing CD and UC. Non-Jewish White smokers were at increased risk of CD (29 studies; relative risk [RR]: 1.95, 95% confidence interval [CI]: 1.69‒2.24; moderate evidence). No association was observed in Asian, Jewish. and Latin-American populations [11 studies; RR: 0.97; 95% CI: 0.83-1.13], with no evidence of heterogeneity across these ethnicities. Smokers were at reduced risk of UC [51 studies; RR: 0.55, 95% CI: 0.48-0.64; weak evidence] irrespectively of ethnicity; however, cohort studies, large studies, and those recently published showed attenuated associations. CONCLUSIONS: This meta-analysis did not identify any increased risk of CD in smokers in ethnicities other than non-Jewish Whites, and confirmed the protective effect of smoking on UC occurrence. Future research should characterise the genetic background of CD patients across different ethnicities to improve our understanding of the role of smoking in CD pathogenesis.

The Need for Culturally Competent Care Within Gastroenterology Services: Evidence from Research with Adults of South Asian Origin Living with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: It is widely acknowledged that the incidence of inflammatory bowel disease [IBD] is rising within South Asian populations, yet research into the experiences of this group of patients is rare. In this study the lived experiences of UK South Asian adults with IBD, including support from gastroenterology services, was investigated. METHODS: A sample of 33 patients representing the diversity of the UK South Asian population were recruited through five gastroenterology clinics in England. In-depth semi-structured interviews were conducted, audio-recorded, transcribed and analysed using the Framework approach. RESULTS: Although many experiences align with those of the general IBD population, participants believed that South Asian cultures and/or religions can lead to additional challenges. These are linked to: family and friends' understanding of IBD; self and family attributions regarding IBD; stigma surrounding ill health; the taboo of bowel symptoms; managing 'spicy food'; beliefs about food and ill health; roles within the family; living with extended family; the use of complementary and alternative therapies; and visits to family overseas. Religious faith helped many to cope with having IBD, but symptoms could hamper their ability to practise faith. Gastroenterology services were viewed positively, but unmet needs were identified, some of which were culturally specific. CONCLUSION: Gastroenterology services have an important role to play in helping patients to overcome the challenges they encounter in their everyday life, both by providing individual patients with culturally appropriate care and advice, and via interventions to increase awareness and understanding of IBD within wider South Asian communities.

Inflammatory Bowel Disease-Associated Changes in the Gut: Focus on Kazan Patients.

BACKGROUND: Several studies have highlighted the role of host-microbiome interactions in the pathogenesis of inflammatory bowel disease (IBD), resulting in an increasing amount of data mainly focusing on Western patients. Because of the increasing prevalence of IBD in newly industrialized countries such as those in Asia, the Middle East, and South America, there is mounting interest in elucidating the gut microbiota of these populations. We present a comprehensive analysis of several IBD-related biomarkers and gut microbiota profiles and functions of a unique population of patients with IBD and healthy patients from Kazan (Republic of Tatarstan, Russia). METHODS: Blood and fecal IBD biomarkers, serum cytokines, and fecal short-chain fatty acid (SCFA) content were profiled. Finally, fecal microbiota composition was analyzed by 16S and whole-genome shotgun sequencing. RESULTS: Fecal microbiota whole-genome sequencing confirmed the presence of classic IBD dysbiotic features at the phylum level, with increased abundance of Proteobacteria, Actinobacteria, and Fusobacteria and decreased abundance of Firmicutes, Bacteroidetes, and Verrucomicrobia. At the genus level, the abundance of both fermentative (SCFA-producing and hydrogen (H2)-releasing) and hydrogenotrophic (H2-consuming) microbes was affected in patients with IBD. This imbalance was confirmed by the decreased abundance of SCFA species in the feces of patients with IBD and the change in anaerobic index, which mirrors the redox status of the intestine. CONCLUSIONS: Our analyses highlighted how IBD-related dysbiotic microbiota-which are generally mainly linked to SCFA imbalance-may affect other important metabolic pathways, such as H2 metabolism, that are critical for host physiology and disease development.

Disparities in Objective Sleep Quality as Assessed Through Wrist Actigraphy in Minority Patients With Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with a reduced quality of life. Minority patients with IBD specifically report more impairing symptoms compared with nonminority patients. Sleep quality, a key component of quality of life, is significantly compromised in minority patients compared with nonminority patients. Nevertheless, subjective and objective sleep assessments in minority patients with IBD have not explicitly been assessed. The purpose of this prospective cohort study is to assess and compare objective sleep parameters utilizing wrist actigraphy between minority and nonminority IBD patients. METHODS: In this institutional review board approved study, 74 patients with IBD were recruited and stratified into 2 cohorts by self-identification: white nonminority patients and minority patients. Patients in the minority cohort included black and Hispanic individuals (black and nonblack). Exclusion criteria included significant comorbidity, a history of an underlying sleep disorder, or patients who did not self-identify into categorized cohorts. Sleep was measured not only through wrist-based actigraphy but also with sleep surveys. Sleep parameters were compared between minority and nonminority cohorts. Regression analyses were performed to assess for factors independently associated with parameters of poor sleep quality. RESULTS: Sixty-four patients (86.4%) were included in the final analysis. Thirty-one individuals (48.4%) were categorized into the nonminority cohort, and 33 (51.6%) patients were in the minority cohort. A significantly higher number of minority patients had poorer sleep efficiency and fragmented sleep compared with nonminority patients (90.9% vs 67.7%; P = 0.03 and 87.8% vs 61.3%; P = 0.02). In the adjusted analysis, minority status was independently associated with poor sleep efficiency (odds ratio = 6.41; 95% confidence interval, 1.48-28.17; P = 0.0139) and fragmented sleep (odds ratio = 4.98; 95% confidence interval, 1.09-22.89; P = 0.0389). CONCLUSIONS: Minority patients with IBD were shown to have poorer objective measures of sleep as assessed through wrist actigraphy compared to nonminority patients. Cultural competency in the care of minority patients with IBD, specifically focusing on the management of psychosocial issues, is needed to address these disparities in sleep. The inclusion of minority patients with IBD in studies investigating sleep and other psychosocial issues are warranted not only to assess potential disparities in disease course but also to determine the etiologies of poor sleep in minority patients with IBD.

Tracking evidences of Coptis chinensis for the treatment of inflammatory bowel disease from pharmacological, pharmacokinetic to clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis (C. chinensis, Huanglian in Chinese), a famous traditional herbal medicine used for clearing heat and detoxification since thousands of years ago, is widely and traditionally used for clinical treatment of stomach inflammation, duodenum and digestive tract ulcers alone or through combing with other herbs in compound formulations. AIM OF THE REVIEW: Through literature reviews of C. chinensis and berberine (one of the most important bioactive compounds derived from this plant) for the treatment of inflammatory bowel disease (IBD), this review aims to provide beneficial information for further exploration of the potent bioactive constituents from C. chinensis, deep investigation on the molecular mechanisms for the treatment of IBD, as well as further research and development of brand new products from C. chinensis for clinical therapy of IBD. METHODS: "C. chinensis" and "IBD" were selected as the main keywords, and various online search engines, such as Google Scholar, PubMed, Web of Science, China National Knowledge Infrastructure database (CNKI) and other publication resources, were used for searching literatures. RESULTS: To present, C. chinensis together with other herbs are involved in plenty of Chinese herbal prescriptions for the treatment of IBD, but little research focused on the single therapeutic effects of C. chinensis or extracts from this herb for the treatment of this disease. Berberine, one of important and representative bioactive compound isolated from C. chinensis, was reported to treat IBD effectively at a big arising speed in recent years. However, systematically and comprehensively reviews on the research of C. chinensis and berberine for the treatment of IBD from the aspects of chemical constituents, pharmacological effects, pharmacokinetics as well as clinical studies are seldom accomplished by researchers. Bioactive components from C. chinensis exert therapeutic effects for the treatment of IBD mainly through the inhibition of oxidative stress, antinociception, protection of intestinal mucosal epithelial barrier, regulation of T helper cells, as well as antibacterial activity. Although numerous studies on bioactive compounds from C. chinense have been performed by clinical investigators in recent years, most of them should be performed in a more strict and standard way to ensure the safety and efficacy of these compounds. CONCLUSIONS: Berberine is considered as the representative and effective component from C. chinensis, but many other chemical components isolated from C. chinensis also have therapeutic effects for the treatment of IBD, which need deep research and further exploration. To accelerate research and development of C. chinensis and its bioactive components for the treatment of IBD, clinical trials are needed to clarify the effectiveness and safety of these chemical components from C. chinensis, as well as their molecular mechanisms for IBD treatment in vitro and in vivo. It is believed that continuous research and exploration on C. chinensis together with its bioactive compounds will bring great hope to the treatment of IBD.

Inflammatory polyps occur more frequently in inflammatory bowel disease than other colitis patients.

BACKGROUND: Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential. AIM: To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC). METHODS: We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed. RESULTS: Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn's disease patients (27% vs. 5%, P < 0.001) within the IBD group. CONCLUSION: Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.

Comparison of Disease Phenotypes and Clinical Characteristics Among South Asian and White Patients with Inflammatory Bowel Disease at a Tertiary Referral Center.

BACKGROUND: The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS: The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS: South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS: A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.

An intronic FTO variant rs16952570 confers protection against thiopurine-induced myelotoxicities in multiethnic Asian IBD patients.

Thiopurines are used in the treatment of inflammatory bowel disease (IBD) but remain clinically challenging to manage due to wide interpatient variability in clinical outcomes and adverse events. Apart from genetic variants in thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15) genes, polymorphisms in FTO alpha-ketoglutarate dependent dioxygenase (FTO) were found predictive of thiopurine-induced leukopenia, albeit with conflicting results. To clarify the role of FTO variants in a multiethnic Asian IBD cohort, we recruited 149 patients on thiopurine-based therapy and genotyped two FTO variants p.Ala134Thr (rs79206939) and rs16952570 T > C using Sanger sequencing. FTO p.Ala134Thr (rs79206939) was non-polymorphic and absent whereas intronic rs16952570 T > C was equally prevalent in Chinese (22%) and Indians (18%) and higher in Malays (28%). Higher nadir white blood cell (WBC) and absolute neutrophil count (ANC) levels were observed in patients harboring FTO rs16952570 CC genotypes compared with TT carriers at 4, 8, and 12 weeks after start of thiopurine therapy (P < 0.05). A similar trend was observed in patients carrying the previously well-characterized NUDT15 rs116855232 wild-type CC genotypes. Further in silico analysis suggests that FTO variants linked to rs16952570, particularly rs74018601, may play a regulatory role in altering the FTO expression. The findings from this study indicate a novel protective association with the FTO variant rs16952570 CC genotype and hematological parameters.

Autoimmune diseases in first- and second-degree relatives of patients with inflammatory bowel diseases: a case-control survey in Israel.

BACKGROUND: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic, relapsing, inflammatory diseases of the gastrointestinal tract with unknown etiology. IBD are complex, multi-factorial disorders, in which genetic factors play a major role, the so-called phenomenon of familial aggregation or clustering of IBD. A positive family history of IBD is often reported among CD and UC probands, with percentages depending on the geographic context in which the studies are carried out. Israel is a complex and pluralistic society comprising of two major ethno-national groups (Arabs and Jewish) and, as such, represents a unique living laboratory in which to test the role of genetic factors in the development of IBD as well as of associated autoimmune disorders (ADs). While some studies have found a lower prevalence of ADs among Arabs when compared to Jews, few studies directly compared the two ethnicities. METHODS: The present case-control study was designed to compare the rate of ADs in first- and second-degree relatives of IBD patients, stratified according to Jewish or Arabic ethnicity. RESULTS: We found that first-degree relatives of Jews patients had a higher risk of developing ADs (OR=1.89, P=0.0086). Classifying ADs into systemic and local (endocrinological, gastrointestinal, dermatological, and neurological) types, first-degree relatives of Jews patients had a higher OR of developing local ADs (OR=2.12, P=0.0056). CONCLUSIONS: Israeli Jewish IBD patients had more first-degree relatives with local ADs as compared to Arab patients.

The Incidence and Prevalence of Inflammatory Bowel Disease in the Jewish and Arab Populations of Israel.

BACKGROUND: Temporal trends in the incidence of inflammatory bowel disease (IBD) in the Arab and Jewish populations in Israel have been poorly described. OBJECTIVES: To compare the annual incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in the Arab and Jewish populations in Israel between the years 2003 and 2008. METHODS: We applied a common case identification algorithm to the Clalit Health Services database to both determine trends in age-adjusted incidence and prevalence rates for IBD in both populations during this period and estimate the burden of IBD in Israel. RESULTS: The incidence of CD in the Arab population increased from 3.1/100,000 in 2003 to 10.6/100,000 person-years in 2008, compared with a decrease in the Jewish population from 14.3/100,000 to 11.7/100,000 person-years for the same period. The incidence of UC in the Arab population increased from 4.1/100,000 in 2003 to 5.0/100,000 person-years in 2008, a low but stable rate, compared with a decrease from 16.4/100,000 to 9.5/100,000 person-years for the same time period in the Jewish population. The prevalence of both diseases increased due to the accumulation of incident cases but remained much lower among Arabs. CONCLUSIONS: Understanding the factors underlying the differences in incidence and prevalence of IBD in the Jewish and Arab populations may shed light on the genetic and environmental factors associated with these diseases.

Characteristics of inflammatory bowel disease in patients of Roma/Gypsy ethnicity. A case-control study.

BACKGROUND: Peculiarities of inflammatory bowel disease (IBD) have been explored in ethnic groups, such as Asians, Hispanics, and Afro-Americans, but not in other ethnic minorities, such as Roma/Gypsies. METHODS: In a retrospective, hospital-based study, all adult Roma/Gypsy patients included in the IBD databases of seven Spanish centres were identified as cases. For each Roma/Gypsy patient, a Caucasian patient, matched for several demographic features, was searched as a control. Data on phenotypic features, therapeutic requirements, and familial aggregation were recorded. RESULTS: Sixty-eight Roma/Gypsy patients were identified, 29 of them being women. The mean age at diagnosis of IBD was 24.9±9.5years, and the mean time elapsed since diagnosis was 96.6±72.2months. Roma/Gypsy IBD patients showed a significantly higher rate of familial aggregation (43%) than their Caucasian controls (9%) (p=0.00001). CD in Roma/Gypsies had more often a complicated pattern (mainly penetrating) while UC patients showed a marked trend to more often developing extraintestinal manifestations. In addition, Roma/Gypsy IBD patients had a somewhat greater need for immunosuppressants, biological agents or surgery. CONCLUSIONS: These are the first data on IBD in Roma/Gypsy patients. Familial aggregation is the most prominent feature in these patients, suggesting a predominant role of genetics in its pathogenesis.

Change in Prevalence of Family History During Long-term Follow-up of Patients With Pediatric-onset Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to prospectively study changes in prevalence of positive family history (FH+) in pediatric-onset inflammatory bowel disease (IBD) in contrast to previously published cross-sectional data. METHODS: An observational cohort study was performed using a prospective pediatric-onset IBD database including 485 patients with disease duration ≥10 years as of December 2016. Proband characteristics and FH+ were obtained at diagnosis and subsequently from the database, medical records, and follow-up telephone interviews in 2006 and 2016. RESULTS: Updated 2016 information was obtained from 322 (66%) patients and included in analysis with median follow-up of 18 years (interquartile range 14, 26). Prevalence of FH+ increased from 13.7% at diagnosis to 26.6% at 20 years for first-degree relatives and from 38.5% to 52.2% for all relatives. At 20-year follow-up, an additional 10.0% of probands had a sibling, 6.1% had a parent, 1.9% had a grandparent, and 4.5% had a cousin diagnosed with IBD. FH+ at diagnosis was associated with greater risk for additional FH+ at 20 years (43% vs 22%, P < 0.001). Non-Jewish Caucasians had significantly lower risk of a FH+ compared to Jewish Caucasians (P = 0.002), but similar risk to African Americans (P = 0.55). FH+ at diagnosis was not associated with disease type (P = 0.33) or age at diagnosis (P = 0.24). CONCLUSIONS: This prospective study documents changes in family history of IBD in pediatric-onset IBD patients over time. Prevalence of FH+ increased for first-degree and all relatives at 20 years by 12.9% and 13.7%, respectively. FH+ at diagnosis was associated with a 2-fold greater likelihood of subsequent FH+ at 20 years.