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Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for > 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC >250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

Background Inflammatory bowel diseases (IBD) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for patients. There is, therefore, a need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD. Methods Label-free quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry (nLC MS/MS) was performed to profile the urinary and serum proteomes of 100 patients with newly diagnosed IBD, before starting any treatment [50 patients with Crohn′s disease (CD) and 50 patients with ulcerative colitis (UC)] and 50 healthy controls (HC). Data Mining and Pattern Recognition techniques were used to identify hidden relationships that are not detectable by using the classical and most commonly used lineal classifiers; and thus, identifying potential markers able to discriminate the studied cohorts. Finally, we applied Ingenuity Pathway Analysis (IPA) to analyze the pathways and functions of differentially expressed proteins. Results Serum proteomics results revealed 45 differentially expressed proteins in the comparison between UC and HC groups, 32 proteins significantly expressed in CD versus HC, and 12 proteins in CD compared with UC. In urine samples, 110 proteins were significantly changed in UC versus HC, 50 proteins were differentially expressed between CD and HC, and a total of 31 proteins were significantly changed in CD compared with UC patients. Receiver operating characteristic curve (ROC) analysis found multiple proteins with high area under the curve values, up to 0.94, indicating that these serum and urine proteins are of value as new non-invasive diagnostic classifiers of IBD patients. For each study comparative, the 5 most significant classifiers were selected (Figures 1 and 2). IPA revealed multiple signaling pathways, including prothrombin activation, acute phase response signaling, complement and coagulation system and liver X receptor/retinoid X receptor (LXR/RXR) activation, altered in IBD patients compared to HC (p-value < 0.05) (Figures 3 and 4). Conclusion Our findings indicate that analysis of the urine and serum proteome using nLC MS/MS is a feasible approach for biomarker discovery. We identified several serum and urine proteins that could serve as new non-invasive markers for the diagnosis of IBD patients after further validation. After bioinformatic analyses, we found multiple proteins that may play important roles in the pathogenesis of IBD.

Background Inflammatory bowel disease (IBD) is a complex multi-factorial disease characterized by chronic inflammation of the gastrointestinal tract. Despite significant efforts to understand the pathogenetic mechanisms of IBD, the elucidation of its etiopathology and progression is far from fully understood. The direct analysis of the intestinal tissue from the endoscopy which leads to IBD diagnosis (before starting any treatment) would be the ideal sample to elucidate IBD pathogenesis. Methods High-throughput mass-spectrometry-based quantitative proteomic analysis was performed using formalin-fixed paraffin-embedded human intestinal samples from newly diagnosed patients to elucidate the potential mechanisms responsible for gut inflammation in Crohn′s disease (CD) and ulcerative colitis (UC). For this purpose, 192 formalin-fixed paraffin-embedded samples from 40 active UC patients, 67 active CD patients and 46 normal biopsies from healthy controls (HC) were analyzed (Figure 1). Proteins with p-value < 0.05 were considered as significantly dysregulated. Moreover, we used Ingenuity Pathway Analysis (IPA) to analyze the pathways and functions in different locations of the gut (ileum or left colon) that could be related to IBD pathogenesis. Results A total of 2,903 proteins were identified, of which 1,010 were differentially expressed between left colon from CD patients and HC. 1,242 proteins were differentially expressed between left colon from UC patients and HC, and 952 differential proteins discriminated between left colon from CD and UC patients. In the comparative study of ileum biopsies from Crohn's disease patients and healthy controls, 956 proteins were differentially expressed (Figure 2). IPA revealed multiple canonical pathways, including EIF2 signaling, regulation of eIF4 and serine/threonine kinase P7056K signaling, mitochondrial dysfunction, and oxidative phosphorylation altered in ileum biopsies from CD patients compared to HC (Figure 3). Regarding the proteomic study in left colon samples, the main canonical pathways enrichment in the comparison of UC and CD with HC were the following: neutrophil extracellular trap signaling pathways, fatty acid oxidation, sirtuin signaling pathway, tRNA charging, and mitochondrial dysfunction (Figure 4). Conclusion The proteomic results revealed dysregulated proteins and pathways in ileum and left colon biopsies from patients with active CD and UC compared to HC that may unravel key mechanisms contributing to the pathogenesis of these diseases. The results of the study serve as a starting point for hypotheses to understand the pathogenesis and search for therapeutic targets.

Background Immune-mediated inflammatory diseases (IMIDs) involve an increased risk of developing atherosclerotic cardiovascular disease (ASCVD). However, the association between inflammatory bowel disease (IBD) and ASCVD is not well established. Our aims were to evaluate the frequency of ASCVD [ischemic heart disease (IHD) and cerebrovascular accident (CVA)] after IBD diagnosis and to identify the risk factors associated with its development. Methods Observational, single-centre study which included all patients seen at the IBD Unit of the Hospital Universitario Central de Asturias (Spain) between May 2010 and April 2022. Cardiovascular risk factors and the development of ASCVD were prospectively assessed; in addition, this information was sought selectively prior to IBD diagnosis and patients’ first visit to the unit. Regarding classical risk factors, we analysed hypertension, dyslipidaemia and diabetes mellitus. As possible risk factors related to IBD, we analysed the presence of complex IBD which, in the case of Crohn's disease (CD), we defined as the presence of stricturing or penetrating behaviour or the need for bowel resection surgery, and, in the case of ulcerative colitis (UC), as an E3 extension or the need for colectomy. Finally, we analysed the coexistence of other IMIDs as a risk factor. Results A total of 2,153 patients were included (52% CD, 45% UC and 3% IBD-unclassified). Forty-nine percent were women and mean age at IBD diagnosis was 39 years. Twenty-four percent had hypertension, 14% dyslipidaemia and 8.6% diabetes; 59% were current or former smokers; 37% had an associated IMID (12% cutaneous and 7.9% joint). Prior to IBD diagnosis, 62 patients had presented with ASCVD (41 IHD and 21 CVA). After IBD diagnosis, 95 patients had at least one ASCVD (49 IHD and 46 CVA); after 31,516 patient-years of follow-up, the incidence of a first ASCVD was 0.31 per 100 patient-years (0.16 IHD and 0.15 CVA). The incidence of ASCVD was stable over time after IBD diagnosis. In the multivariate analysis (Table 1), age at IBD diagnosis >50 years (p Table 1. Figure 1. Figure 2. Conclusion The development of ASCVD in patients with IBD is associated with classical risk factors (hypertension and dyslipidaemia), as well as older age at diagnosis and male sex. The coexistence of other IMIDs does not increase the risk of ASCVD in these patients.

Background It has been suggested that the transition of patients from paediatric to adult care units may be key in the outcomes of inflammatory bowel disease (IBD). However, the impact of transition in real clinical practice has been barely studied. Aims: Principal: to evaluate the impact of transition on clinical outcomes in IBD. Secondary: to describe the prevalence of transition programs in Spain; to identify predictive factors of poor clinical outcomes; and to evaluate the percentage of patients with loss to follow-up. Methods Multicenter, retrospective, and observational study of IBD patients transferred between 2017-2020. Two groups (transition/no-transition) were compared retrospectively. Transition was defined as a structured process with at least 1 join visit involving the gastroenterologist, paediatrician, and a program coordinator, as well as the parents and the patient. Outcomes within the first 12 months after transfer were analysed. The main variable was the presence of “poor clinical outcome” defined as an IBD flare, hospitalisation, surgery or any change of the treatment due to an IBD flare. Predictive factors of poor clinical outcome were identified in multivariate analysis. Results A total of 278 patients from 34 Spanish hospitals were included: 185 patients (67%) from 22 hospitals (65%) performed a structured transition. In hospitals without transition, 91% of the patients were transferred to an IBD-specialist. In 66% of the patients in the transition group, 1 joint visit was performed. The median age of transfer was 16 years [interquartile range (IQR)=12-20]. Baseline characteristics of both groups are detailed in Figure 1. At 1-year after transfer, hospitalisations and corticosteroid treatment were more frequent in the no-transition group (10 vs. 3%; p=0.025; 16 vs. 5%; p=0.002). At 1-year after transfer, 89 patients (27% transition vs. 43% no-transition; p=0.005) had poor clinical outcome [median time: 9.3 months; 95% confidence interval (CI)=8.4-10.1 in no-transition; 10.4 months (95%CI 9.9-10.9) in the transition group]. In the multivariate analysis, the lack of transition [Hazard Ratio (HR)=2.1; 95%CI=1.4-3.3], IBD activity at transfer (HR=4.9; 95%CI=3.1-7.9), BMI Conclusion In the present study, to our knowledge the largest performed so far, the benefit of paediatric to adult transition program on patients’ outcomes has been demonstrated. The importance of achieving remission before transfer has also been highlighted.

Background The etiology and pathogenesis of inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are complex and the mechanisms that lead to the development of these diseases remain unclear. Extracellular vesicles (EVs) are small particles covered with a cell membrane, originating from the emitting cell, excreted into the extracellular medium, and subsequently captured by receptor cells. EVs have a role in multiple diseases and they could also have a function in IBD pathogenesis. Therefore, the analysis of EVs isolated from the serum of newly diagnosed IBD patients (before starting any treatment) may represent an appropriate experimental approach to elucidate their role in IBD pathogenesis. We aimed to evaluate EVs’ composition and potential effects in the pathogenesis of IBD. Methods The protein content of EVs isolated by size exclusion chromatography from the 500 µl of serum from 100 patients with IBD (50 patients with CD and 50 patients with UC) recently diagnosed and 50 healthy controls (HC) was characterized by proteomics and their size and concentration in serum by Nanoparticle tracking analysis (NTA). The biological function of EVs and alterations in signaling pathways related to IBD were determined using Ingenuity Pathways Analysis (IPA) to analyze the OMICs results. Results A total of 1,100 proteins have been identified, of which 105 proteins were differentially expressed by patients with CD versus HC, 111 proteins by patients with UC versus HC, and 32 proteins by patients with UC versus CD. IPA analysis revealed that proteins carried in EVs are involved in the dysregulation of immune pathways such as the acute phase response (Figure 1), LXR/RXR activation pathway (Figure 2), and the complement pathway. These pathways were regulated differentially in IBD patients compared with HC, but also when the CU group was compared with the CD group (Figure 3) being upregulated nuclear receptors signaling and cytotoxicity pathways. Conclusion EVs carry proteins that can be involved in the dysregulation of the immune system in IBD; this effect would be different in UC and CD since their EVs show a differential profile. Consequently, EVs may play role in IBD pathogenesis and source of strong biomarkers candidates for diagnosis in UC and CD. Further studies on their specific function during IBD are warranted.

Background The association of several immune-mediated inflammatory diseases (IMIDs) in the same patient is well known. IMID, especially joint and cutaneous diseases, are frequently diagnosed in patients with inflammatory bowel disease (IBD). However, the degree of knowledge that patients with IBD have about the coexistence of other IMIDs is little studied. Our aim was to evaluate the accuracy of self-reporting of IMID by patients with IBD. Methods Prospective, unicentric study that included patients attended in person at the IBD Unit of the Central University Hospital of Asturias (Spain) between August 2020 and December 2021. Patients were invited to participate in the study, and, after signing the informed consent, they answered a questionnaire about the presence or not of 50 IMIDs (self-reported diagnosis). The diagnosis of an IMID was confirmed in the medical records of each patient (reference diagnosis). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy (proportion of subjects correctly classified) of self-reporting was calculated. Statistical analyses were performed with R software version 4.0.2. Results A total of 1,621 patients were included. Forty-four percent of patients had ulcerative colitis, 53% had Crohn's disease and 3% had an IBD-unclassified, 50% were men, and the age at diagnosis of IBD was 38±15.2 years. Seven hundred and twelve patients were receiving mesalazine, 67 corticosteroids, 394 immunomodulators and 532 biologics. Six hundred and twenty-seven (39%) patients were diagnosed with at least one IMID, 177 (10.9%) with two, 49 (3%) with three, and 17 (1%) with more than three. Sixteen percent of patients had a joint IMID and 15% a cutaneous IMID. Self-reporting of IMID by IBD patients has a sensitivity, specificity, PPV, NPV and accuracy of 0.75 (95% CI 0.73-0,78), 0.89 (95% CI 0.86-0.91), 0.92 (95% CI 0.89-0.93), 0.69 (95% CI 0.66-0.73) and 0.81 (95% CI 0.79-0.83), respectively. Table 1 shows the results by IMID groups (joint, cutaneous, digestive, endocrinological, ocular, others), and Table 2 shows the results of the most frequent IMIDs. Conclusion Eighty-one percent of patients with IBD are able to correctly identify the coexistence or not of IMIDs. It was observed that in the case of joint IMIDs there is a significant percentage of patients who do not know whether or not they suffer from one of these diseases.

Background Main aim: To evaluate the retention rate of ustekinumab compared to vedolizumab in Crohn’s disease patients who failed anti-TNF therapy in clinical practice. Secondary aims: To compare the short-term and long-term effectiveness, and the safety of both treatments. Methods Crohn’s disease patients who had received either vedolizumab or ustekinumab after failure or intolerance to anti-TNF agents from ENEIDA registry were included. ENEIDA is a prospectively maintained database promoted by GETECCU. A total of 755 patients from 30 centres were included at time of data extraction. Clinical activity was classified based on Harvey-Bradshaw index both at short (during induction) and in the long-term. Kaplan-Meier curves, Cox regression models, inverse probability weighting and propensity matching score analyses were performed to compare both drugs and to identify predictive factors of treatment effectiveness and durability. Results 755 patients were included (195 in the vedolizumab cohort and 560 in the ustekinumab cohort). After a median of 20 months (IQR 7.4–30) of follow-up, the survival rate for ustekinumab therapy was higher than vedolizumab (Figure 1). The propensity matching score verified the differences between both therapies. The short-term proportion of patients on clinical remission, steroid-free remission and clinical response was also superior in the ustekinumab cohort (Figure 2). In the long-term, significant differences were observed 2 years after the beginning of the treatments, although no differences in clinical response and remission rates were detected in patients who achieved clinical response at week 16 between both cohorts. Vedolizumab was discontinued in 142 patients and ustekinumab in 185, mainly due to primary non-response (52% in the vedolizumab and 58% in the ustekinumab cohort) and loss of response (34% and 25%, respectively) despite the fact that 35% of the patients required intensification. The predictive factors associated to the discontinuation of the therapy are described in table 1. Adverse events were observed, overall, in 12% of the patients, without differences between both groups (Table 2). Following the discontinuation of the treatment with vedolizumab/ustekinumab, other biologic agents were prescribed in 56% of the patients, and 27% underwent surgery. Conclusion In clinical practice, a relatively high proportion of Crohn’s disease patients who received ustekinumab or vedolizumab for anti-TNF failure, maintained these drugs in the medium-long term, although ustekinumab retention rate was higher in comparison with vedolizumab.

Background Patients with inflammatory bowel disease (IBD) are often classified as ulcerative colitis (UC) and Crohn’s disease (CD). However, in some cases this categorization is not possible and these patients are labelled as inflammatory bowel disease unclassified (IBDU) -or indeterminate colitis if histologic analysis of surgical specimens is possible-.The aims of this study were to compare the prognosis and therapeutic requirements in patients with IBDU and UC, and to identify potential predictive factors of reclassification as UC or CD. Methods Retrospective, observational, multicenter and case-control study of Spanish ENEIDA registry promoted by GETECCU. IBDU patients were identified from 18 centers. Every case of IBDU was matched with 2 patients of ulcerative colitis of the same hospital by sex, age at diagnosis and disease extent (in the patchy colitis subgroup, every case was matched with 1 extensive colitis and 1 left colitis). Results 231 IBDU patients and 469 UC patients were included. Only 15 IBDU patients met current criteria of indeterminate colitis. In the IBDU group 59.7% patients were males and the mean of age at diagnosis was 43.3 years. Disease extent was distributed in 14 proctitis, 59 left-sided colitis, 87 extensive colitis and 53 patchy colitis. 13.9% had rectal sparing and 31.9% presented ileitis. Thirteen percent were smokers at diagnosis, 5.6% had perianal disease and 15.9% had extraintestinal manifestations. Table 1: baseline characteristics of IBDU and UC group. When comparing IBDU to UC patients, there were no statistical differences between proportion of patients that needed immunosuppressants (35.7% vs 37.7%, p=0.558) and biological therapy (27.3% vs 24.3%, p=0.415). Regarding surgery for medically refractory disease, UC patients had higher surgical rates, although these differences did not reach statistical significance (2.6% vs 0.5%, p= 0.062). Figure 1: immunosuppressants, biological and surgery rates. Overall mortality rates were similar in both groups (5.1% in IBDU vs 2.6% in UC); with only one case related to IBD in IBDU group. During follow-up, 67 IBDU patients (31%) were reclassified (32 UC, 34 CD, 1 indeterminate colitis). 25% of patients were reclassified within 46 months of follow-up (Figure 2: Kaplan-Meier curve of reclassification). Neither clinical, biochemical (C- reactive protein, albumin, hemoglobin) nor endoscopic variable (rectal sparing, ileitis) was associated with change in diagnosis. Conclusion In clinical practice, there were no statistical differences in prognosis, therapeutic requirements and surgical treatment between IBDU and UC patients. Two thirds of patients remained classified as IBDU during the follow-up. No predictive factors of reclassification have been identified.

Background The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) to avoid colectomy and change the natural history of the disease. The effectiveness and safety of sequential treatment should be evaluated in this scenario. Main aim To evaluate colectomy-free survival in patients with ASUC refractory to intravenous steroids who had failed infliximab (IFX) or ciclosporin (CyA) and received a second salvage therapy. Secondary aims: To evaluate the short-term and long-term effectiveness and to assess the safety of this strategy. Methods Multicentre study of patients admitted with ASUC refractory to corticosteroids who failed CyA or IFX and had received a second salvage therapy during the same hospital stay. Clinical activity was classified based on partial Mayo score and Lichtiger activity index. Patients who stopped second-line therapy due to disease activity or adverse events were considered as failures. Short-term colectomy-free survival was assessed by logistic regression analysis while long-term colectomy-free survival was evaluated by Kaplan-Meier curves and Cox regression models. Results Results: A total of 78 patients from 24 centres were included. As first-line therapy, IFX was administered to 32 patients, and CyA to 46. Baseline characteristics are detailed in table 1. The prescribed salvage therapy was IFX in 45 patients, CyA in 17, tofacitinib in 13, and ustekinumab in 3 (Figure 1). Colectomy was required in 29 patients (37%) during the follow-up (median 14 days, IQR 3-23). Colectomy-free survival curves are shown in figure 2-A and 2-B. Second-line salvage therapy with CyA was associated with a higher rate of colectomy (Figure 2-C). A total of 39 patients (55%) at week 12 and 20 patients (33%) at month 12 had clinical response; 31 patients (44%) at week 12 and 18 (30%) at month 12 were in clinical remission. At the last visit of the study, 26 patients (33%) were still under the second-line therapy. Adverse events (AE) were recorded in 26 patients (33%), being serious in 15. Resolution with no sequelae was observed in 20 patients (77%). No differences in AE between the second-line therapies prescribed were observed. There were two deaths: one due to cerebral thrombophlebitis and another due to bacteriemia after colectomy, both when CyA was the salvage therapy prescribed (Table 2). Conclusion A second-line salvage therapy avoids colectomy in a considerable percentage of patients admitted by ASUC and therefore it could be considered after IFX or CyA failure. The individual therapeutic approach must be discussed with patients due to the risk of serious adverse events.

Background Oral corticosteroids remain as the first-line treatment for moderately active ulcerative colitis (UC). In controlled studies, they achieved clinical remission in 30-60% of patients at 30 days. In severe systemic diseases, intravenous bolus administration of methyl-prednisolone accelerates the clinical response and increases the therapeutic efficacy of corticosteroids. Aims To assess the additive effect of IV boluses of methyl-prednisolone in an outpatient Schedule on the remission rate of moderately active UC. Methods Randomized, controlled, open study. Inclusion criteria: 1) moderately active (complete May 6-10) distal or extensive UC; 2) never exposed to immunosuppressants or biologicals; 3) without corticosteroid therapy within the last 6 months. Randomization to oral prednisone 60mg/day (ORAL arm) or the same regimen preceded by intravenous boluses of 500mg methyl-prednisolone for 3 days (BOLUS arm). Primary endpoint: clinical and endoscopic remission at week 8 as defined by a complete Mayo score 1. Results are expressed in frequencies, medians and interquartile range. Results 75 patients (39 ORAL, 36 BOLUS) were included, 24% at diesease onset, 49% extensive UC, 68% were on maintenance with oral 5ASA, and 31% had ever received systemic corticosteroids. At baseline, complete Mayo score was 9 (7-9), with C-reactive protein 9.25 mg/L (3.85-20.17) and fecal calprotectin 1430 ug/g (501-2702), with no differences in the baseline clinical-epidemiological characteristics between both treatment arms. At 8 weeks, 37% of patients achieved clinical-endoscopic remission (47% BOLUS vs 28% ORAL; p=0.089), 52% mucosal healing -Mayo endoscopic subscore Conclusion The addition of three intravenous megaboluses at the beginning of a conventional regimen of oral prednisone achieves a non-significant increase in clinical-endoscopic remission rates at the end of corticosteroid treatment in patients with moderately active UC.

Background Very few studies have reported updated data on the incidence, clinical evolution and treatment of inflammatory bowel disease (IBD) in Europe. Aims i) To assess the incidence of IBD in Spain; ii) to describe the main epidemiological and clinical characteristics of patients at diagnosis and the evolution of the disease; and iii) to explore the use of drug treatments in the biological era. Methods Prospective and population-based nationwide registry. Adult patients diagnosed with IBD -Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)- during 2017 in all the 17 Spanish administrative regions were included and will be followed-up for 5 years after diagnosis. Treatment was grouped into 5 categories: mesalazine (oral or topical), steroids (intravenous, oral or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab or ustekinumab) and surgery. Results 3627 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 millions of adult inhabitants (about 50% of the Spanish population) comprise the study cohort (Table 1). The overall incidence (cases/100.000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U. Incidence of CD was somewhat higher in Central Spain, while that of UC was higher in Northern Spain (Asturias and Navarra) (Figure 1). About 46% of patients had CD and 50% UC. Diagnosis delay was longer in CD than in UC (5 vs. 2 months, p < 0.01). The proportion of patients with symptoms at diagnosis was higher in UC than CD (94 vs. 89%, p < 0.01). By contrast, those with CD vs. UC had higher frequency of family history of the disease (18 vs. 13%, p < 0.01), tobacco smoking (38 vs. 12%, p < 0.01) and extraintestinal manifestations (12 vs. 6%, p < 0.01). At diagnosis, 18% of CD patients had structuring or fistulising behaviour, and 69% of UC patients had extensive colitis or left-sided colitis. During a median of 12-month of follow-up, 28% of patients were hospitalised (35% of CD and 22% of UC patients, p < 0.01). A total of 2.6% CD patients progressed to a more severe phenotype, and 2% UC patients developed a more extensive involvement. The cumulative exposure to different treatments is shown in Figure 2. Conclusion The incidence of IBD in Spain is quite high and similar to that reported in Northern Europe. IBD patients require the use of substantial therapeutic resources, which are greater in CD than in UC, and much greater than previously reported. One third of patients are hospitalised in the first year after diagnosis and over 5% undergo surgery. These results highlight the high burden of IBD as well as some of the important challenges faced by clinicians and healthcare systems to manage this costly and complex disease.

Background Aims: 1) to compare persistence on adalimumab treatment over time in inflammatory bowel disease (IBD) patients who maintained adalimumab reference [non-switch cohort (NC)] vs. those who switched from adalimumab reference to adalimumab biosimilar [switch cohort (SC)]; 2) to compare loss of effectiveness of adalimumab treatment in the NC vs. SC; 3) to identify factors associated with discontinuation of adalimumab therapy; 4) to identify the factors associated with relapse in both cohorts; and 5) to evaluate the safety of both strategies. Methods Retrospective, observational, multicentre study. Patients under adalimumab reference who were in clinical remission at standard dose of adalimumab reference, and in whom adalimumab was the first anti-TNF administered, were included. Clinical remission was defined as a Harvey-Bradshaw index ≤4 points in Crohn’s disease, a partial Mayo score ≤2 in ulcerative colitis, and the absence of fistula drainage despite gentle finger compression in perianal disease. The follow-up time was at least 6 months since start of study observation period. The Kaplan-Meier method with log-rank test was used to evaluate the cumulative incidence of treatment discontinuation. Cox regression model was used to investigate factors potentially associated with therapy discontinuation. Results A total of 505 patients were included (45% women, 87% Crohn’s disease): 229 in the SC and 276 in the NC. The median follow-up was 12 months in the SC and 23 months in the NC (p0.05). Conclusion The incidence rate of relapse was slightly higher in the SC; however, this fact had no impact on persistence on the drug. Switching from adalimumab reference to adalimumab biosimilar was safe.

Background Currently, endoscopy is the gold standard for the evaluation of disease activity and inflammation in clinical practice. However, it is an invasive procedure for the patient, costly and time-consuming. Therefore, there is an urgent need to identify non-invasive biomarkers with the potential clinical utility to diagnose inflammatory bowel disease (IBD) patients, improve the patient′s quality of life and increase efficiency in the Health Systems. Methods A label-free quantitative proteomics method was used to profile the urinary and serum proteomes of 100 patients with newly diagnosed IBD, before starting any treatment [50 patients with Crohn′s disease (CD) and 50 patients with ulcerative colitis (UC)] and 50 healthy controls (HC). The resulting peptides were separated by NanoLC (EVOSEP ONE) and coupled online by electrospray to Trapped Ion Mobility Spectrometry (TIMS) TOF Pro for tandem mass spectrometry analysis. Mass spectrometry data were processed and analyzed with MaxQuant and Perseus software. Proteins with p≤0.05 and ratio>1.5 in any sense, were considered as significantly dysregulated. Bioinformatic analysis of differentially expressed proteins was performed to characterize involved biological processes, molecular functions, cell locations and proteins pathways (PANTHER and STRING v11.5). Results A total of 2,500 proteins were identified in the urine, and 468 proteins were identified in the serum with at least two different peptides at FDR Conclusion Proteome profiling revealed significantly differences in newly diagnosed patients with CD or UC. Both serum and urine seem to be appropriate biological matrixes for this approach. Next steps of our research will be to understand the role of candidate proteins as well as to validate those with potential as biomarkers in independent cohort.

Background Clinical trials and real-life studies with Ustekinumab in Crohn’s disease show its good efficacy and safety profile. However, there are hardly any data on elderly patients, who are excluded from these clinical trials. Our aim is to evaluate these variables in real-life practice. Methods Retrospective analysis of patients from the prospectively maintained ENEIDA registry treated with Ustekinumab for Crohn’s disease. Elderly patients were selected as those over 60 years old at the start of treatment. They were compared with 2 randomised controls from the same centre, aged less than 60 years, matched for smoking habit. The degree of comorbidity was assessed using the Charlson’s index. Clinical and biochemical activity and effectiveness were defined based on Harvey-Bradshaw index and calprotectin and CRP levels at weeks 16, 32 and 54, when available. Results A total of 648 patients were analysed, 212 elderly (mean age 67 [63.6;72.8] years) and 436 young (mean age 41.6 [32.6;50.0] years). No differences were observed between both groups in baseline variables except for the degree of comorbidity, higher in elderly patients (1.00 [0.00;2.00] vs 0.00 [0.00;0.00], p Clinical response rate was similar in both groups at week 16 (70.5% vs 76.6%, p=0.199), week 32 (67.6% vs 70.2% p=0.104) and week 54 (74% vs 74.9%, p=0.326). Steroid-free remission and biochemical response also showed no differences throughout follow-up. The rate of adverse effects was similar in both groups (14.2% vs 11.2%, p=0.350) except for the occurrence of de novo neoplasms, which was higher in the elderly group (0.69% vs 4.25%, p=0.003). The rate of severe infections (7.08 vs 7.34, p=1.000), the need for surgery (16.5% vs 20.0%, p=0.345) and the need for hospital admission (21.7% vs 19.0%, p=0.489) did not differ. Persistence of UST treatment was similar in both groups (log Rank test p=0.91). Conclusion Ustekinumab achieved clinical response in almost three-quarters of elderly patients, similar to the younger population, with no increase in the rate of infections or other adverse effects, with the exception of de novo neoplasms.

Background Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer. Dye-based chromoendoscopy (CE) is the currently recommended method for the detection of dysplasia in IBD surveillance colonoscopy; the role of virtual chromoendoscopy (VCE) is not yet well defined. To compare CE with VCE using iSCAN1 digital image enhanced colonoscopy in the detection of colonic neoplastic lesions in IBD patients. Methods Randomised, single-centre trial to assess the detection rate of colonic neoplastic lesions in patients with long-standing IBD. Patients were randomised in two arms: dye-spraying CE using indigo carmine and electronic VCE using iSCAN1 digital image. Detection rates of dysplasia or any neoplastic lesion were compared by the two endoscopic techniques. Results A total of 129 patients were studied (67 by CE and 62 by VCE). Demographic and clinical characteristics were homogeneous in the two groups; 26 Crohn′s disease and 103 ulcerative colitis, 52% women, mean age 50 years, median duration of IBD 204 months, family history of colorectal cancer in 10 (8%), associated primary sclerosing cholangitis in 8 (6%), personal history of colorectal dysplastic lesions in 12 (9%), and more than 50% colonic involvement in 72 (56%). In total, 27 lesions (9 hyperplastic, 8 adenomatous and 10 low-grade dysplasia) were detected in 23 patients, without differences between CE and VCE arms (15 [22%] and 12 [19%] lesions, respectively; p = 0.98); on the other hand, neoplastic lesion (dysplasia or adenoma) detection rates was similar (12 [18%] in CE and 6 [10%] in VCE arms, p = 0.2). The duration of the withdrawal time of colonoscopy in minutes for patients in the CE group was median 14 min and in the VCE group was median 10 min (p < 0.001). Conclusion There is no statistical difference between CE and VCE using iSCAN1 in the detection rate of colonic neoplastic lesions in IBD patients. Surveillance colonoscopy with VCE (iSCAN1) spends less time than conventional CE.

Resumen Introduccion La falta de adhesion al tratamiento con 5-ASA es un factor predictivo significativo de recaida en colitis ulcerosa. Este estudio se ha realizado con el fin de investigar la percepcion que tienen sobre la colitis ulcerosa los distintos profesionales sanitarios con los que trata el paciente en el transcurso de su enfermedad. Material y metodos El estudio se diseno como una investigacion cualitativa mediante grupos de discusion entre medicos de atencion primaria (n = 4), gastroenterologos (n = 4) y enfermeros de gastroenterologia (n = 4). Resultados Entre las posibles causas de incumplimiento terapeutico senaladas en este estudio se mencionaron la falta de concienciacion del paciente al no tener sintomas, la mala comunicacion, o bien afecciones psiquiatricas como la ansiedad y la depresion. Los tres colectivos profesionales opinaron que reducir el numero de tomas diarias podria contribuir a una mayor adhesion terapeutica. Todos los profesionales que participaron en este estudio senalaron la falta de comunicacion entre ellos, especialmente entre atencion primaria y atencion especializada, a pesar de ser conscientes de su relevancia. Conclusion La falta de cumplimiento en CU es un problema complejo que puede implicar muchos factores, como la falta de concienciacion ante la ausencia de sintomas, el temor a los efectos adversos y una mala comunicacion medico-paciente. Se describieron como aspectos fundamentales que podrian mejorar la adhesion: simplificar el tratamiento a una toma diaria y fomentar la comunicacion tanto con el paciente como entre los distintos niveles asistenciales.

Resumen El uso de anticuerpos contra el factor de necrosis tumoral alfa (anti-TNF) aumenta el riesgo de tuberculosis (TB) en pacientes con enfermedad inflamatoria intestinal (EII). GETECCU publico las primeras guias de cribado de TB para pacientes con EII en 2003 y las reviso en 2006. Sin embargo, la implementacion en la practica clinica de nuevas pruebas diagnosticas como los test de liberacion de interferon gamma, el mayor conocimiento epidemiologico y clinico de la TB en el contexto de tratamiento anti-TNF y la evidencia de que las recomendaciones de cribado de infeccion tuberculosa latente en pacientes candidatos a terapia anti-TNF disminuye pero no erradica los casos de TB han motivado la revision de las recomendaciones de GETECCU al respecto.

Resumen La enfermedad inflamatoria intestinal (colitis ulcerosa, enfermedad de Crohn y colitis no clasificada) precisa un manejo global encaminado al diagnostico, tratamiento, seguimiento y prevencion de complicaciones. Para su manejo se han creado unidades encargadas de proporcionar una atencion integral al paciente, pero sin menoscabar el papel que debe realizarse en el ambito de la Atencion Primaria (AP). Los medicos de AP deben conocer los sintomas pero, ademas, ante un paciente con sospecha de enfermedad inflamatoria, deben disponer de pruebas sanguineas y fecales y de pruebas de imagen como la ecografia que pueden ayudar al diagnostico. Asimismo, desempenan un papel importante en el seguimiento, en la deteccion precoz de agudizaciones y en la puesta en marcha de medidas encaminadas a prevenir la aparicion de complicaciones relacionadas con la propia enfermedad, los farmacos administrados o las secuelas de la malnutricion o cirugias previas.

To describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP) associated with gluten enteropathy (GE).We prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22%) in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE.A total of 34 patients (18%) met clinical-biological criteria for GE (group1), and were compared to the remaining non-GE AP cases (n=161) (group2). Mean age in the GE group was 54 +/- 25 years, slightly younger than group 2 (61 +/- 14) (NS). There was a mild predominance of women (50%) in group 1 versus group 2 (38.5%) (NS). Seven patients in group 1 (20%) had severe AP, as compared to 27 (17%) in group 2 (NS). The presence of cholelithiasis in group 1 involved 6 cases (18%), which was significantly lower than in group 2--72 cases (45%) (p0.05). Four patients with GE developed pseudocysts (12%) versus 13 (8%) in group 2 (NS). Tissue transglutaminase (tTG) was elevated only in 3 patients (9%). Nine patients (34%) were DQ2 (+) and 4 (12%) DQ8 (+); the rest (54%) were all negative for both markers. From an endoscopic perspective there was diffuse duodenitis in 32 patients (95%). Duodenal biopsies revealed villous atrophy (Marsh 3) in 2 patients (6%); submucosal inflammatory infiltration (Marsh 2) in 10 (29.4%); increased intraepithelial lymphocytes (Marsh 1) in 8 cases (23.5%), and normal mucosa (Marsh 0) in 14 patients (41.2%). Response to GFD after 1 year was excellent in 30 patients (88%).Relapsing AP with GE represents a relatively common association that is indistinguishable from other APs from a clinical-evolutive standpoint, except for a lower presence of cholelithiasis (p0.05). A specific diagnostic protocol is much needed in the identification of these patients since GFD is the only effective therapy to prevent new AP events from developing.

celiac disease (CD) is an autoimmune condition that is triggered by the ingestion of gluten, a substance present in most cereals, and that affects genetically predisposed individuals. As a result, this condition is clearly familial, and mainly associated with HLA class II markers.in this work we set out to analyze the prevalence of CD in an extensive family based on an index subject who had already died from this disease a few years ago, where CD had been complicated by the development of a small-bowel malignancy, namely an adenocarcinoma.nineteen members were studied. They all were subjected to a diagnostic protocol including a detailed medical history, hemogram, coagulation tests, and blood biochemistry (including liver function tests, serum iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8). Suspect cases underwent gastroscopy plus multiple duodenal biopsy for confirmation.overall we encountered CD in 9/19 studied members, which represents 47.4% with the following distribution according to degree of kinship -four of seven siblings (57%); one of three children (33.3%); three of eight nephews and nieces (37.5%), and the only grandnephew, who was 9 years old.from all this it may be seen that family studies are needed every time a patient is diagnosed with celiac disease; these studies should include both first- and second-degree relatives, given the high prevalence encountered and the fact that these tests are relatively straighforward to perform.

The epidemiologic analysis inflammatory bowel disease (IBD) is a powerful research tool to assess the contribution of environmental factors to its etiology. IBD has been reported to have varying frequencies in different parts of the world, and there seem to be significant differences in the disease pattern and clinical course. The aim of the present study was to assess the disease pattern of IBD in Asturias (Spain).A descriptive epidemiological population based study, retrospective (1954-1993) and prospective (1994-97), was performed to study 1018 patients found, bigger than 14 years, to have IBD, in five areas of Asturias (Spain) (461.965 inhabitants).During the period of time studied, we diagnosed 1018 IBD [565 ulcerative colitis (55.5%), 415 (40.8%) Crohn's disease and 38(3.7%) indeterminate colitis], with 482 females (47.2%), 536 males (52.8%), and male/female: 1.11. Age at diagnosis were 39.49 +/- 1.08 (95% CI : 38.41 +/- 40.57); (UC: 43.95 +/- 1.47; CD: 33.53 +/- 1.51; IC: 38.26 +/- 5.14. p = 0.000. Age at onset previously at diagnosis for UC: 42.84 +/- 1.34; CD: 30.68 +/- 1.40; IC: 36.74 +/- 4.86 (p = 0.000). Diagnosis criteria: UC: syntomatic 97.34% (p = ns), endoscopy 96.63% (p = 0.000 pathology 90.26% (p = 0.000). CD: radiology 83.61% (p =0.000). Study level in CD: 57.57 (p = 0.0005). Family history: 8.4%. The most frequent involvement at diagnosis of UC was proctitis only, in 13.6%, 269% rectum and sigmoid 26% let colitis, 20% pancolitis, and in CD colon only, in 16.7%, 30.3% terminal ileum, 41.3% ileo-colon of the patients. This also helps to explain the differences in severity, need for surgery, and survival noted between community based studies.We highlight the uniformity of distribution of the inflammatory bowel disease in relation to types and sex. The high frequency of familial Crohn's disease suggests a genetic predisposition. Highlighting a bigger morbilidad for the Crohn's Disease reflected in the surgical requirements, but however with smaller mortality that in ulcerative colitis.

To know and to compare Inflammatory Bowel Disease (IBD) Incidence and Prevalence rates in in five areas of Asturias (Spain). We conducted a prospective epidemiologic study of IBD in the Province of Liege (1 million inhabitants).We conducted a descriptive, populational, collaborative epidemiologic study, retrospective between 1954 and 1993 and prospective between 1994 and 1997. All patients diagnosed according to a standard protocol for case ascertainment and definition of IBD, aged 14 years or more are included, in five areas of Asturias (Spain) (461,965 inhabitants).For the period 1954 to 1997, 1018 IBD have been diagnosed [565 ulcerative colitis (UC) (55.5%), 415 Crohn's disease (CD) (40.8%) and 38 undefined IBD (IC) (3.7%)]; [482 women (47.2%), 536 males (52.8%)]. In the 4 year-prospective period, 306 cases were collected: 176 UC (57.51%), 110 CD (35.94) and 20 IC (6.53%); UC/CD: 1.6. Without appreciable and significant differences between Frequency of illness groups and sexes. IBD incidence rate (per 100,000 per year) (1954-97) is 5.12 (95% CI = 3.05-7.18) (UC: 2.84; CD: 2.08; IC: 0.19; UC/CD 1.36). In the 4 years- prospective study, IBD incidence rate is 16.55 (95% CI = 12.84-20.25), (UC: 9.52; CD: 5.95; IC: 1.08; UC/CD: 1.6). IBD prevalence rate in 1997 is 205.21 (95% CI = 182.14-227.29), (UC: 109.96; CD: 87.45; IC: 7.79). Comparisons have settled down among the studied areas, without finding differences statistically significant.Inflammatory Bowel Disease incidence and prevalence rates of in our region are homogeneous between the cities investigated and superior than those historically reported in Spanish studies. These results were similar to those observed in European studies.

Objetivo: La epidemiología de la enfermedad inflamatoria intestinal crónica (EIIC) es una poderosa herramienta de investigación que contribuye a la evaluación de los factores medioambientales que influyen en su etiología. El objetivo de este estudio es conocer distintos aspectos epidemiológicos de la EIIC en nuestro medio. Pacientes y métodos: Estudio epidemiológico descriptivo, poblacional, multicentrico, retrospectivo entre 1954 y 1993 y prospectivo entre 1994 y 1997. Se incluyen 1018 enfermos mayores de 14 años, diagnosticados de EIIC en 5 áreas del Principado de Asturias (España), con un censo de 461.965 habitantes. Resultados: Del total de 1018 identificados [565 CU (55,5%) (incluyendo proctitis), 415 EC (40,8%) y 38 CI (3,7%)], 482 son mujeres (47,2%) y 536 varones (52,8%), con una relación V/M de 1,11. La edad media al diagnóstico es de 39,49 ± 1,08 (IC; 95%: 38,41 - 40,57), [CU: 43,95 ± 1,47; EC: 33,53 ± 1,51; CI: 38,26 ± 5,14]. p = 0,000. La edad media de inicio de síntomas previo al diagnóstico es 37,66 ± 0,97 (CU: 42,84 ± 1,34; EC: 30,68 ± 1,40; CI: 36,74 ± 4,86 (p = 0,000). El diagnóstico de CU ha sido posible con criterios clínicos en el 97,34% (p = ns), criterios endoscópicos en el 96,63% (p = 0,000) y criterios histológicos en el 90,26% (p = 0,000). En la EC: criterios radiológicos 83,61% (p = 0,000). El nivel cultural es superior en la EC: 57,57 (p = 0,0005). Asociación familiar del 8,4%. Extensión: en la CU: proctitis 13,6%, 26,9% colitis distal, 26% colitis izquierda, 6% colitis extensa y el 20% pancolitis; En la EC el 30,3% tienen afectación de íleon terminal, el 16,7% colon, el 41,3% colon e intestino, el 11,7% son intestinales extensas y el 3,7% tienen afectación gastro-duodenal; En la CI destaca un 39,5% de afectación discontinua. La media de cirugías necesarias para el control de la enfermedad es de 0,44 ± 6,11, (26,62% de los enfermos). CU: 0,12 ± 3,33 (9,91%); EC: 0,91 ± 12,9 (50,36%), p = 0,000. Tasa de Mortalidad de 47,15 /1000 habitantes (CU: T = 61,94; EC: T = 26,50; CI: T= 0,004) p = 0,046. RMS: 0,467 (CU: 6,14; EC: 2,63; CI: 100). Conclusiones: Este estudio que abarca una importante población de enfermos, pretende aportar nuestros resultados epidemiológicos a la Enfermedad Inflamatoria Intestinal Crónica. Nuestros resultados no difieren substancialmente de los de otras publicaciones. La colitis ulcerosa y la enfermedad de Crohn así como el sexo, se distribuyen uniformemente. La elevada asociación familiar entre estas enfermedades sugiere un origen genético de la EIIC. La enfermedad de Crohn se expresa con mayor morbilidad reflejada en los requerimientos quirúrgicos, pero sin embargo con menor mortalidad que en la colitis ulcerosa.

Objetivo: Conocer y comparar la incidencia y prevalencia de la enfermedad inflamatoria intestinal cronica (EIIC) en 5 areas del Principado de Asturias (Espana). Pacientes y metodos: Estudio epidemiologico descriptivo, poblacional, multicentrico, retrospectivo entre 1954 y 1993 y prospectivo entre 1994 y 1997. Se incluyen todos los enfermos mayores de 14 anos, diagnosticados de EIIC segun un protocolo estandar para el diagnostico y definicion, en 5 areas del Principado de Asturias, con un censo de 461.965 habitantes. Resultados: En el periodo de tiempo estudiado, han sido diagnosticados 1018 enfermos con EIIC [565 CU (55,5%), 415 EC (40,8%) y 38 CI (3,7%)]; [482 mujeres (47,2%), 536 varones (52,8%)]. En el periodo de 4 anos de estudio prospectivo, se identifican 306 EIIC: 176 CU (57,51%), 110 EC (35,94) y 20 CI (6,53%); CU/EC: 1,6. La frecuencia de aparicion de los distintos grupos de enfermedad no presenta diferencias significativas, asi como tampoco existen diferencias entre ambos sexos. La tasa de incidencia media anual (1954-97) en EIIC es 5,12 (IC 95% = 3,05 - 7,18) (CU: 2,84; EC: 2,08; CI: 0,19; CU/EC 1,36). En el periodo de tiempo de estudio prospectivo, la tasa de incidencia media anual de la EIIC es 16,55 (IC 95% =12,84 - 20,25), (CU: 9,52; EC: 5,95; CI: 1,08; CU/EC: 1,6). La prevalencia, referida a 1997 para la EIIC es de 205,21 (IC 95% = 182,14-227,29), (CU: 109,96; EC: 87,45; CI: 7,79). Se han establecido comparaciones entre las areas estudiadas, sin encontrar diferencias estadisticamente significativas. Conclusiones: Las tasas brutas de incidencia y de prevalencia de la enfermedad inflamatoria intestinal cronica en nuestro medio son superiores a las historicamente descritas en otras areas de nuestro pais y similares a las publicadas en poblaciones de alta incidencia. No hemos encontrado diferencias significativas entre las cinco areas que componen el estudio. Objetivo: Conocer y comparar la incidencia y prevalencia de la enfermedad inflamatoria intestinal cronica (EIIC) en 5 areas del Principado de Asturias (Espana). Pacientes y metodos: Estudio epidemiologico descriptivo, poblacional, multicentrico, retrospectivo entre 1954 y 1993 y prospectivo entre 1994 y 1997. Se incluyen todos los enfermos mayores de 14 anos, diagnosticados de EIIC segun un protocolo estandar para el diagnostico y definicion, en 5 areas del Principado de Asturias, con un censo de 461.965 habitantes. Resultados: En el periodo de tiempo estudiado, han sido diagnosticados 1018 enfermos con EIIC [565 CU (55,5%), 415 EC (40,8%) y 38 CI (3,7%)]; [482 mujeres (47,2%), 536 varones (52,8%)]. En el periodo de 4 anos de estudio prospectivo, se identifican 306 EIIC: 176 CU (57,51%), 110 EC (35,94) y 20 CI (6,53%); CU/EC: 1,6. La frecuencia de aparicion de los distintos grupos de enfermedad no presenta diferencias significativas, asi como tampoco existen diferencias entre ambos sexos. La tasa de incidencia media anual (1954-97) en EIIC es 5,12 (IC 95% = 3,05 - 7,18) (CU: 2,84; EC: 2,08; CI: 0,19; CU/EC 1,36). En el periodo de tiempo de estudio prospectivo, la tasa de incidencia media anual de la EIIC es 16,55 (IC 95% =12,84 - 20,25), (CU: 9,52; EC: 5,95; CI: 1,08; CU/EC: 1,6). La prevalencia, referida a 1997 para la EIIC es de 205,21 (IC 95% = 182,14-227,29), (CU: 109,96; EC: 87,45; CI: 7,79). Se han establecido comparaciones entre las areas estudiadas, sin encontrar diferencias estadisticamente significativas. Conclusiones: Las tasas brutas de incidencia y de prevalencia de la enfermedad inflamatoria intestinal cronica en nuestro medio son superiores a las historicamente descritas en otras areas de nuestro pais y similares a las publicadas en poblaciones de alta incidencia. No hemos encontrado diferencias significativas entre las cinco areas que componen el estudio.

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

Helicobacter pylori is a worldwide infection, and it is estimated that approximately 50% of the general population is affected. However, its distribution varies considerably between developed and developing countries.in the present study we report the results of an epidemiological investigation of the prevalence of H. pylori infection in the general population in Asturias (Northern Spain), in order to describe the current state of this infection in our region, and obtain figures for comparison with the results obtained in different communities of Spain and other countries.a descriptive transversal, epidemiological study, based on the serological determination of the IgG antibodies against H. pylori was carried out in the general population of a randomly selected sample of subjects without previous gastroduodenal antecedents.we analyzed 480 serum samples obtained from the general population of Asturias. These were divided into decades according to the age pyramid and tested for the presence of antibodies against H. pylori with a commercially available latex agglutination technique (Pyloriset).the global prevalence of H. pylori infection in our study was 226/480 (49.2%), and was slightly higher in women (50.6%) compared to men (47.6%). No significant differences were found between sexes (p = 0.51). In the first decade mean prevalence was 13.6%. In the second this figure was 25.4%, and it increased steadily to a maximum in the sixth decade of 76.4%. Thereafter, the prevalence decreased to 66.6% in persons over 80 years of age.we found a high prevalence approximately 50% of H. pylori infection in the general population of Asturias, as in other epidemiological studies in Spain and other European countries. The distribution according to age shows a clear tendency to increase, from childhood to adolescence and adult life (50-60 years), when prevalence is highest (76%). From this decade onwards it begins to decrease, showing a clear cohort effect with a pattern intermediate between that of developed and developing countries.

The aim of this study was to know the prevalence, epidemiology, clinical manifestations and analytical changes present in anti-HCV positive blood donors detected in Asturias.A prospective analysis of the incidence and prevalence of anti-HCV positivity in the blood donations carried out in Asturias from October 1989 to October 1991 was performed, as was a clinical and analytical study of the anti-HCV positive cases who attended a clinic specifically created for the same.The prevalence of the anti-HCV was 0.87% of the donors (372/42,789) and 0.50% of the donations (372/73,831) being higher among new donors (1.77%, 165/9,322). Of the 288 cases studied (77.4%), only 51 (17.7%) had been transfused and 105 (36.5%) lacked the previous parenteral risk factor. Only 31 (10.8%) presented symptoms or signs of liver disease and the positivity of the anti-HBc was not associated to any relevant analytical change. The existence of previous major surgery or transfusion was variable with the independent predictive value versus a negative anti-HCV control group. The mean follow up was 12.4 +/- 7.3 months (6-30 months) with an increase in aminotransferases (ALT) being detected in 108 cases (52.7%). A good correlation was found between this data, an ELISA-2 score greater than 5 and RIBA-2 positivity: of the 177 cases in whom RIBA-2 was determined this was found to be positive in 109 (61.6%); 84 cases (77.1%) had an increase in ALT and 100 (91.8%) an ELISA-2 score greater than 5.In Asturias the prevalence of anti-HCV positivity among blood donors is almost 1% and is greater if new donors are considered, being confirmed by RIBA-2 in 61% of the cases. The subjects are usually asymptomatic and up to one third of the same lack any known risk factor, while almost half have hypertransaminasemia during follow up.

A comparative study of the differences with respect to prevalence, epidemiologic risk factors, clinical and analytical status and histologic data of blood donors with different liver diseases detected in the same geographical area and time period was carried out.HBsAg or anti-HCV positive blood donors detected in Asturias (Spain) from October 1989-1991, and a third group of 115 consecutive donors with negative viral markers and an increase in ALT, as well as a fourth control group with no alterations were compared with a BMDP statistical program and logistic regression analysis.The prevalence of anti-HCV+ donors was greater than that of those with HBsAg+ in both general donors (0.87% vs 0.28%) as well as in new donors (1.77% vs 1.2%) with a constant incidence of HBsAg+ cases of around 0.16% of the donations with a decrease being observed in the anti-HCV+ (ELISA 1) cases from 0.76% to 0.25%. The mean age was significantly higher among the anti-HCV+ donors with respect to the remaining groups (41 vs 36 years). Likewise, the cases of anti-HCV+ presenting parenteral risk factors, such as intravenous drug addiction, transfusion or surgery were significantly higher, with the latter two having an independent predictive value. Signs or symptoms of liver disease were more frequently detected in the anti-HCV+ (10.8%) vs the HBsAg+ (2.3%) as were an increase in ALT (52.8% vs 12.7%) and histologic signs of chronic hepatitis (36.4% vs 6.9%).Anti-HCV+ blood donors more frequently present previous parenteral risk factors, signs or symptoms of chronic liver disease, hypertransaminasemia or histologic data of chronic hepatitis, thus its detection in al altruistic blood donor indicates a high probability of chronic subjacent liver disease. This is in contrast to donors with HBsAg+ which do not normally present liver disease and those with hypertransaminasemia with negative viral markers who generally have slight liver lesions.

We report three cases of "Dieulafoy's gastric erosion" or "Exulceratio simplex", which is rarely recognized but is not an uncommon cause of upper gastrointestinal hemorrhage, usually very dangerous, as it's an arterial bleeding. In all cases an emergency endoscopy was performed, and treatment with combination of local sclerosis and vessel's electrocoagulation was successful. We insist in the potential benefits of endoscopic treatment in all these occasions, if it's possible, since even exact diagnosis of the bleeding site is very difficult in some patients.

We report the case of a patient with ulcerative colitis and autoimmune hemolytic anemia, that improved with steroid therapy, and during the follow-up showed analytical changes of iron deficiency anemia and anemia of chronic disorders. We discuss the possible etiologies of the anemia in patients with ulcerative colitis, and the treatments suggested for the associated Coombs-positive hemolytic anemia in these cases, stressing the good response to steroids in our patient.

The aim of the present study was to know the current prevalence of HBsAg positivity in Asturias blood donors and to carry out a clinical study of the carriers of the hepatitis B virus (HBV) accidentally detected in a blood donation program.A prospective study of incidence and prevalence of HBsAg positivity in blood donations performed in Asturias over two years from October 1989 and 1991 was carried out and the epidemiologic, clinical, and analytical characteristics, as well as histologic liver lesions in the HBsAg positive cases were determined.Among the 42,789 blood donors during this above mentioned period in Asturias 119 cases of HBsAg positivity were found, representing a prevalence of 0.16% of the donations and 0.28% of the donors, generally new donors (95.8%) with a prevalence of 1.2% in this subgroup. No risk factors or known source of contagion were found in 43.6% of the cases and in most occasions the donors were asymptomatic HBsAg carriers (96.5%) with normal transaminases (87.3%) with 4.6% of the cases being HBeAg positive and 3.5% being mutant "e minus" carriers.The prevalence of HBsAg was almost limited to new donors with a higher prevalence being observed with respect to other regions. Most of the cases may be considered as "apparently healthy" and in the group with positive replicative markers a similar number of positive HBeAg carriers and "e minus mutants" were present.

We report the case of a 22-year-old man with a craniopharyngioma, who developed ascites following a ventriculoperitoneal shunt procedure for hydrocephalus. The ascites was resolved with diversion of the distal catheter into the right atrium. A ventriculoperitoneal shunt can cause ascites, even without neurological symptoms suggestive of shunt malfunction.

We studied the prevalence of antibodies to hepatitis C virus (anti-HCV) among 164 heterosexual partners of anti-HCV-positive subjects, 131 prostitutes and 52 homosexual men. 6.7% of heterosexual monogamous partners had anti-HCV; the seropositivity rate was associated with a long-term sexual practice and with age. Of the 131 prostitutes, 6 (4.6%) had anti-HCV; there were significant associations in patients positive for anti-HCV, with a history of parenteral drug addiction. 11.5% of homosexual men were anti-HCV positive; there were significant associations with positivity for antibodies to HIV, intravenous drug abuse and with the number of sexual partners. We concluded that the HCV may be transmitted by sexual route, but the high seroprevalence among prostitutes and homosexuals may be explained by other parenteral mechanisms.

We have determined the prevalence of antibodies against hepatitis C virus (anti-HCV) in 45 patients with primary biliary cirrhosis (PBC) and 6 with autoimmune chronic active hepatitis (AI-CAH). Anti-HCV was positive in two cases of PBC, both with a history of previous blood transfusion, and in one patient with AI-CAH, only during an active phase of the disease.